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HiTZ zentroa 55

[ "Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are a microdeletion at 16p13.3 or mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) at 22q13 (5%). Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots. Thus about 55% of patients have cytogenetic or molecular abnormalities in the Crebbp or E1A binding protein p300 (Ep300) gene, leaving the diagnosis in 45% of patients to rest on clinical features only." ]

[ "Mutations or/and deletions in the genes of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) at 22q13 (5%)." ]

[ "The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features", "Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3", "these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-AMP-regulated gene expression", "RTS was shown to be associated with disruption of the CREB-binding protein gene CBP (CREBBP), either by gross chromosomal rearrangements or by point mutations", "Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease", "A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS)", "In 92 patients, we were able to identify a total of 36 mutations in CBP", "We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder.", "Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS).", "Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations.", "It could be possible that genetic heterogeneity is related with novel mutations in other genes.", "identified a novel CREBBP missense mutation, c.2728A > G (predicting p.Thr910Ala)", "The p.Thr910Ala variant is outside the crucial histone acetyltransferase domain, and this may explain the mild and variable phenotype", "Rubinstein-Taybi syndrome (RSTS), a developmental disorder comprising abnormalities that include mental retardation, an unusual facial appearance, broad thumbs and big toes is frequently associated with molecular lesions in the CREB-binding protein gene, CREBBP", "Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots in which ten novel pathogenic mutations were localized" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23432975", "http://www.ncbi.nlm.nih.gov/pubmed/16359492", "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "http://www.ncbi.nlm.nih.gov/pubmed/20684013", "http://www.ncbi.nlm.nih.gov/pubmed/18773673", "http://www.ncbi.nlm.nih.gov/pubmed/22303793", "http://www.ncbi.nlm.nih.gov/pubmed/7630403", "http://www.ncbi.nlm.nih.gov/pubmed/14974086", "http://www.ncbi.nlm.nih.gov/pubmed/20689175", "http://www.ncbi.nlm.nih.gov/pubmed/22991675", "http://www.ncbi.nlm.nih.gov/pubmed/22269667" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:1933" ]

[ "The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels." ]

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[ "antifungal protein KP4", "Killer protein 4 (KP4) is a well studied viral toxin secreted by the maize smut fungus Ustilago maydis that kills sensitive Ustilago strains as well as inhibits Fusarium and plant root growth by inhibiting calcium uptake.", "Our previous work on a virally encoded fungal toxin, KP4, from Ustilago maydis and subsequently with the plant defensin, MsDef1, from Medicago sativa demonstrated that some of these proteins specifically blocked calcium channels in both fungi and animals.", "The results presented here demonstrate that KP4 and three plant defensins, MsDef1, MtDef2, and RsAFP2, all inhibit root growth in germinating Arabidopsis seeds at low micromolar concentrations", ". There are three well-characterized killer toxins in U. maydis-KP1, KP4, and KP6-which are secreted by the P1, P4, and P6 subtypes, respectively. These killer toxins are small polypeptides encoded by segments of an endogenous, persistent double-stranded RNA (dsRNA) virus in each U. maydis subtype.", "The viral gene for the killer protein 4 (KP4) has been explored for its antifungal effect", "antifungal protein KP4 from Ustilago maydis-infecting virus", "The antifungal activity correlated with the presence of the KP4 transgene.", "These results suggest that KP4 may inhibit cell growth and division by blocking calcium-regulated signal transduction pathways.", "KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis.", "KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis.", "Our results defining the type of mammalian channel affected by this fungal toxin further support our contention that KP4 inhibits fungal growth by blocking transmembrane calcium flux through fungal calcium channels,", "Killer toxins are polypeptides secreted by some fungal species that kill sensitive cells of the same or related species. In the best-characterized cases, they function by creating new pores in the cell membrane and disrupting ion fluxes", "KP4 is a virally encoded and highly specific toxin that kills fungi closely related to the fungus Ustilago maydis.", "The P4 strain of the corn smut fungus, Ustilago maydis, secretes a fungal toxin, KP4, encoded by a fungal virus (UMV4) that persistently infects its cells.", "These results led to experiments demonstrating that the toxin specifically inhibits voltage-gated Ca2+ channels in mammalian cells.", "Ustilago maydis killer toxins are small polypeptides (7-14 kDa) which kill susceptible cells of closely related fungal species. The KP4 toxin is a single polypeptide subunit with a molecular weight of 11.1 kDa" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7582897", "http://www.ncbi.nlm.nih.gov/pubmed/11901234", "http://www.ncbi.nlm.nih.gov/pubmed/21116630", "http://www.ncbi.nlm.nih.gov/pubmed/7966296", "http://www.ncbi.nlm.nih.gov/pubmed/10748529", "http://www.ncbi.nlm.nih.gov/pubmed/8145639", "http://www.ncbi.nlm.nih.gov/pubmed/17849147", "http://www.ncbi.nlm.nih.gov/pubmed/17522822", "http://www.ncbi.nlm.nih.gov/pubmed/8809749", "http://www.ncbi.nlm.nih.gov/pubmed/11532143", "http://www.ncbi.nlm.nih.gov/pubmed/21303448", "http://www.ncbi.nlm.nih.gov/pubmed/8616260" ]

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[ "http://www.biosemantics.org/jochem#4265993", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014764", "http://www.uniprot.org/uniprot/KP4T_UMV4" ]

[ "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells. Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. Monitoring Aire expression in MSCs may thus be a critical parameter for clinical use." ]

[ "stem cell renewal and self-immune tolerance" ]

[ "Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "Instead, Aire reduced T cell mitochondrial reductase by negatively regulating a proinflammatory cytokine, early T cell activation factor (Eta)-1.", "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells", "Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance", "Mutations in the autoimmune regulator (AIRE) protein cause a breakdown of central tolerance that is associated with decreased expression of self antigens in the thymus", "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.", "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells", "Aire promotes the self-renewal of embryonic stem cells through Lin28.", " Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21952165", "http://www.ncbi.nlm.nih.gov/pubmed/19302042", "http://www.ncbi.nlm.nih.gov/pubmed/19008896", "http://www.ncbi.nlm.nih.gov/pubmed/20226168", "http://www.ncbi.nlm.nih.gov/pubmed/22540148" ]

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[ "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. ", "A powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs was termed PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation). PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions. It relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise.", "AR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteinsOne characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. ", "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. ", "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions " ]

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[ "We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs.", "To gain insight into the complexity of snoRNA processing and the functional relevance of snoRNA-derived small RNAs, we sequence long and short RNAs, small RNAs that co-precipitate with the Argonaute 2 protein and RNA fragments obtained in photoreactive nucleotide-enhanced crosslinking and immunoprecipitation (PAR-CLIP) of core snoRNA-associated proteins.", "A large amount of miRNA-target interactions (MTIs) have been identified by the crosslinking and immunoprecipitation (CLIP) and the photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) along with the next-generation sequencing (NGS)", "PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions", "A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation.", "In this article, we review crosslinking and immunoprecipitation (CLIP) methods adapted for large-scale identification of target RNA-binding sites and the respective RNA recognition elements.", "CLIP methods have the potential to detect hundreds of thousands of binding sites in single experiments although the separation of signal from noise can be challenging.", "We focus on photoactivatable ribonucleoside-enhanced CLIP, which relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise.", "Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins.", "The strength of this versatile method results from induction of specific T to C transitions at sites of interaction.", "PAR-CLIP reveals a collection of RNAs bound to a protein whereas SILAC-based RNA pull-downs identify a group of proteins bound to an RNA. ", "Here we present a step-by-step protocol and guidelines for the computational analysis for the large-scale identification of miRNA target sites in cultured cells by photoactivatable ribonucleoside enhanced crosslinking and immunoprecipitation (PAR-CLIP) of AGO proteins.", "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking.", "rosslinking and immunoprecipitation (CLIP) protocols have made it possible to identify transcriptome-wide RNA-protein interaction sites", "In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing.", "ross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins.", "We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites.", "In order to increase the specificity and positional resolution, a strategy referred to as CLIP (UV cross-linking and immunoprecipitation) was introduced.", "Recently, PAR-CLIP was introduced that uses photoreactive ribonucleoside analogs for cross-linking", "AR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteins", "We developed a powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs that we term PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation)", "The method relies on the incorporation of photoreactive ribonucleoside analogs, such as 4-thiouridine (4-SU) and 6-thioguanosine (6-SG) into nascent RNA transcripts by living cells. ", "One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22152485", "http://www.ncbi.nlm.nih.gov/pubmed/21816340", "http://www.ncbi.nlm.nih.gov/pubmed/21851591", "http://www.ncbi.nlm.nih.gov/pubmed/20371350", "http://www.ncbi.nlm.nih.gov/pubmed/22213601", "http://www.ncbi.nlm.nih.gov/pubmed/21559008", "http://www.ncbi.nlm.nih.gov/pubmed/23706177", "http://www.ncbi.nlm.nih.gov/pubmed/23368412", "http://www.ncbi.nlm.nih.gov/pubmed/22844102", "http://www.ncbi.nlm.nih.gov/pubmed/22926237", "http://www.ncbi.nlm.nih.gov/pubmed/22885304", "http://www.ncbi.nlm.nih.gov/pubmed/24297251", "http://www.ncbi.nlm.nih.gov/pubmed/21572407", "http://www.ncbi.nlm.nih.gov/pubmed/20644507" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722" ]

[ "Amiodarone-induced thyrotoxicosis treatment includes anti-thyroid drugs and steroid therapy\nRadio Iodine Treatment (RIT) may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.\nLithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone.\nThyrodectomy may be necessary in presence of unresponsiveness to standard medical treatments" ]

[ "Antithyroid drugs", "Corticosteroids", "Lithium", "Radioiodine" ]

[ "good response to anti-thyroid drugs and steroid therapy", "The disease course of amiodarone-induced thyrotoxicosis is usually benign and remits with timely administration of anti-thyroid medications, with or without corticosteroids.", "RIT may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.", "Treatment consists in the use of a high dose of anti-thyroid drugs and steroids in an isolated form or in combination.", "the addition of lithium carbonate to the two other drugs resulted in a successful and safety therapy in controlling amiodarone-induced thyrotoxicosis.", "lithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone.", "Two patients with amiodarone-induced thyrotoxicosis were treated successfully with potassium perchlorate and carbimazole while treatment with amiodarone was continued.", "Amiodarone-induced thyrotoxicosis seems to be a transient condition that can be treated successfully with a short course of antithyroid drugs without stopping amiodarone treatment.", "Both patients were successfully treated with propylthiouracil (PTU) and dexamethasone (DXT)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16910349", "http://www.ncbi.nlm.nih.gov/pubmed/2781955", "http://www.ncbi.nlm.nih.gov/pubmed/19675515", "http://www.ncbi.nlm.nih.gov/pubmed/9217642", "http://www.ncbi.nlm.nih.gov/pubmed/12727944", "http://www.ncbi.nlm.nih.gov/pubmed/16544025", "http://www.ncbi.nlm.nih.gov/pubmed/7946779", "http://www.ncbi.nlm.nih.gov/pubmed/21135419", "http://www.ncbi.nlm.nih.gov/pubmed/11901034" ]

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[ "Diagnosis of spastic diplegia is mainly carried out with through clinical gait analysis (CGA), with variations such as 1-minute walk, LSU, and 10-meter walk tests, or Gross Motor Function Measure-88 (GMFM-88). Other methods used for evaluation of patients include brain magnetic resonance imaging (MRI) and motor function, presence of epileptic episodes, and IQ or developmental quotient.", "Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of Hereditary Spastic Paraplegia (HSP) and Spastic Diplegia (SD). Argininaimia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia. Gait Analysis (GA) complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns." ]

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[ "Spastic diplegia is the most common form of cerebral palsy worldwide.", "Hereditary spastic paraplegia (HSP) and spastic diplegia (SD) patients share a strong clinical resemblance. Thus, HSP patients are frequently misdiagnosed with a mild form of SD. Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD", "The predominant clinical feature of patients with Hereditary Spastic Paraparesis (HSP) is gait disturbance owing to spasticity and weakness of the lower limbs; the spasticity in early-onset disease (infancy or childhood) often cannot be distinguished from mild form of spastic diplegia (SD)", "The aim of this study was to quantify the gait strategy in HSP and SD children, focusing on the differences between groups as concerns functional limitation during gait. 9 HSP and 16 SD children were evaluated using Gait Analysis; kinematic and kinetic parameters and EMG pattern during walking were identified and calculated to compare the two gait strategies", "In contrast to other urea cycle disorders, hyperammonemic encephalopathy is rarely observed in patients with argininemia. Rather, most exhibit an insidious onset and progression of neurologic manifestations, including spastic diplegia.", "We conclude that argininemia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia, even in a population where argininemia was previously unknown", "To assess the reliability and validity of a newly described classification of sagittal plane alignment in spastic diplegic gait.", "The objective of this prospective study was the application of proton magnetic resonance spectroscopy in children with spastic diplegia (SD) to determine the metabolite profile of SD children in the left basal ganglia, and to assess the relationship of this profile with motor and mental developmen", "The aim of this study was to establish the reliability and validity of visual gait assessment in children with spastic diplegia, who were community or household ambulators, using a modified version of the Physicians Rating Scale, known as the Observational Gait Scale (OGS).", "The aim of this study was to analyse quantitatively the gait of HSP and SD subjects in order to define the gait pattern in HSP and the differences between the two conditions", "This study shows that GA complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns.", "nstruct validity of the In-Hand Manipulation Test (IMT) by assessing the test's ability to discriminate between samples of children with and without known fine motor problems.METHOD: The IMT was administered to 55 children without known fine motor problems and 24 children with spastic diplegia who had mild to moderate fine motor problems.", "A discriminant analysis indicated that IMT total score correctly classified 83.33% of the participants as having or not having fine motor problems.", "Calcaneal gait or deformity can be a significant complication after heel cord lengthening. After heel cord lengthening, 20 children with spastic diplegia were evaluated by gait analysis to define calcaneal gait objectively and describe associated morbidity.", "Significant differences were found in birth weight, birth head circumference, and the one-minute Apgar score", " Intracranial hemorrhage and neonatal seizures occurred significantly more often in infants with SD", "On the Movement Assessment of Infants at 4 months of age, the children with hemiplegia and quadriplegia showed significantly higher risk scores than the nonhandicapped group", "At 1 year of age, however, the Bayley Motor Scale was extremely sensitive in picking up motor deficits in children with all three types of cerebral palsy.", "Hip flexion combined with knee extension (leg elevation) and isolated knee movements were not seen in diplegic infants, but were seen in all control preterm infants with a good prognosis, after five and six months corrected age, respectively. The absence of these movements is a useful diagnostic item for spastic diplegia.", "Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia", "Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD. Previous analysis has focused on the lower-body but not the upper-body, where numerous compensations during walking occur. The aim of this study was to compare the full-body movements of HSP and SD groups and, in particular, the movement of the upper limbs", "The study subjects were eight patients with spastic diplegia and eight normal children. Three-dimensional gait analysis was used for the survey. The measured gait variables were the joints of the lower extremity in the sagittal plane, frontal plane, and transverse planes and the maximum and minimum angles of their stance phase and swing phases", "Relationships between spasticity, strength, gait, and the GMFM-66 in persons with spastic diplegia cerebral palsy.", "[Purpose] This study aimed to investigate the effects of Vojta therapy on spatiotemporal gait parameters in children with spastic diplegia. [Methods] The study population consisted of 3 children diagnosed with spastic diplegia.", "The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy (HIVE). A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia.", "The results demonstrated that HSP patients used more spine movement to compensate for lower limb movement alterations, whereas SD patients used their arms for compensation", "To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia", "To examine the validity and clinical utility of functional assessments (1-minute walk test, 10-meter walk test, Timed Up&Go [TUG] test, Timed Up and Down Stairs [TUDS]test, sit-to-stand [STS] test, and lateral step-up [LSU]test)", "These functional assessments (1-minute walk, LSU, and 10-meter walk tests) are simple to administer, quick, low cost, and user-friendly. Although these assessments are not a substitute for the criterion standard (GMFM-88), they may be used for a quick assessment in adolescents with cerebral palsy (levels I-III) either at school or during rehabilitation, especially when time is limited", "The aim of this study was to evaluate the effect of dynamic bilateral postural stability on balance control and gait parameters in children with cerebral palsy.DESIGN: Thirty children with spastic diplegia (8-10 yrs) were included in this study" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2816867", "http://www.ncbi.nlm.nih.gov/pubmed/24901761", "http://www.ncbi.nlm.nih.gov/pubmed/15157997", "http://www.ncbi.nlm.nih.gov/pubmed/1743414", "http://www.ncbi.nlm.nih.gov/pubmed/25276040", "http://www.ncbi.nlm.nih.gov/pubmed/24409030", "http://www.ncbi.nlm.nih.gov/pubmed/17509240", "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "http://www.ncbi.nlm.nih.gov/pubmed/24182356", "http://www.ncbi.nlm.nih.gov/pubmed/23121133", "http://www.ncbi.nlm.nih.gov/pubmed/10427678", "http://www.ncbi.nlm.nih.gov/pubmed/7270517", "http://www.ncbi.nlm.nih.gov/pubmed/25700542", "http://www.ncbi.nlm.nih.gov/pubmed/2600179", "http://www.ncbi.nlm.nih.gov/pubmed/21310339", "http://www.ncbi.nlm.nih.gov/pubmed/24239880", "http://www.ncbi.nlm.nih.gov/pubmed/16344032", "http://www.ncbi.nlm.nih.gov/pubmed/17826455", "http://www.ncbi.nlm.nih.gov/pubmed/20829081", "http://www.ncbi.nlm.nih.gov/pubmed/12549749" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:10965" ]

[ "Neurofibromatosis type 1 (NF1) is due to all types of mutations in the neurofibromin (NF1) gene." ]

[ "Mutation in NF1 gene." ]

[ "Neurofibromatosis type 1 and Noonan syndrome are both common genetic disorders with autosomal dominant inheritance.", "Molecular analysis showed a missense mutation in exon 25 of the NF1 gene (4288A>G, p.N1430D)", "Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1", "Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions.", "Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature.", "Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome affecting approximately 1 in 4,000 persons. It is an autosomal-dominant disorder with half of the cases resulting from spontaneous mutations.", "Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors", "Ninety-one tumors from 31 NF1 patients were screened for gross changes in the NF1 gene using microsatellite/restriction fragment length polymorphism (RFLP) markers; loss of heterozygosity (LOH) was found in 17 out of 91 (19%) tumors (including two out of seven MPNSTs). Denaturing high performance liquid chromatography (DHPLC) was then used to screen 43 LOH-negative and 10 LOH-positive tumors for NF1 microlesions at both RNA and DNA levels. Thirteen germline and 12 somatic mutations were identified, of which three germline (IVS7-2A>G, 3731delT, 6117delG) and eight somatic (1888delG, 4374-4375delCC, R2129S, 2088delG, 2341del18, IVS27b-5C>T, 4083insT, Q519P) were novel. A mosaic mutation (R2429X) was also identified in a neurofibroma by DHPLC analysis and cloning/sequencing.", "The region of DNA located between two translocation breakpoints has been cloned and a DNA sequence encoding a 11-13 kb mRNA identified. That this sequence shows deletions and point mutations in NF1 affected individuals and not in normal controls provides strong evidence that it is indeed the NF1 gene." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16835897", "http://www.ncbi.nlm.nih.gov/pubmed/16323217", "http://www.ncbi.nlm.nih.gov/pubmed/21567923", "http://www.ncbi.nlm.nih.gov/pubmed/14722917", "http://www.ncbi.nlm.nih.gov/pubmed/2129297" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025542", "http://www.uniprot.org/uniprot/NF1_RAT", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016514", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009456", "http://www.uniprot.org/uniprot/NF1_HUMAN", "http://www.uniprot.org/uniprot/NF1_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020022", "http://www.disease-ontology.org/api/metadata/DOID:8712", "http://www.uniprot.org/uniprot/NF1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820" ]

[ "Selenoprotein P, that contains 10 selenocysteines." ]

[ "Selenoprotein P" ]

[ "selenoprotein P and several other selenoproteins are known to contain multiple selenocysteines", "Sepp1) is a secreted protein that is made up of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines", "selenoprotein P genes encode multiple UGAs and two SECIS elements", "Human selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA", "SeP) is an extracellular glycoprotein with 8-10 selenocysteines per molecule", "human, bovine and rodent selenoprotein P genes encode proteins containing 10-12 selenocysteines", "Selenoprotein P is unique in that its mRNA encodes 10-12 selenocysteine residues", "The deduced polypeptide sequence comprises 380 residues including ten selenocysteines", "selenoprotein-P", "selenoprotein P-like protein containing 12 selenocysteines ", " rat and human selenoprotein P cDNA but contained 12 rather than 10 TGAs" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15104205", "http://www.ncbi.nlm.nih.gov/pubmed/15777501", "http://www.ncbi.nlm.nih.gov/pubmed/11122377", "http://www.ncbi.nlm.nih.gov/pubmed/7637580", "http://www.ncbi.nlm.nih.gov/pubmed/19345254", "http://www.ncbi.nlm.nih.gov/pubmed/20417644", "http://www.ncbi.nlm.nih.gov/pubmed/17000762", "http://www.ncbi.nlm.nih.gov/pubmed/9288402", "http://www.ncbi.nlm.nih.gov/pubmed/10692426" ]

[]

[ "http://www.biosemantics.org/jochem#4275372", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051149", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051140" ]

[ "r3Cseq is an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results." ]

[ "r3Cseq" ]

[ "r3Cseq: an R/Bioconductor package for the discovery of long-range genomic interactions from chromosome conformation capture and next-generation sequencing data.", "We present r3Cseq, an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results. We further demonstrate its use on a series of real-world applications", "r3Cseq: an R/Bioconductor package for the discovery of long-range genomic interactions from chromosome conformation capture and next-generation sequencing data" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23671339" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009693" ]

[ "There are no reports on clinical trials of off-label drugs in neonates. An analysis of Pediatric Investigation Plans submitted between 2007 and 2010 shows that neonates were included in the study of 4 products, but it is unknown if the trial drugs are off-label and if the trials are being conducted at all." ]

[ "none", "0", "zero" ]

[ "Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. CONCLUSIONS: The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use.", "Paediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20821198" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007231", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018849" ]

[ "Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis. ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism.", "Yes, stress granules (SGs) have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)." ]

[ "yes" ]

[ "SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).", "Like several other ALS-associated proteins, CREST is recruited to induced stress granules.", "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. ", "Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS.", "Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis.", "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis.", "Fused in sarcoma (FUS) belongs to the group of RNA-binding proteins implicated as underlying factors in amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. Multiple FUS gene mutations have been linked to hereditary forms, and aggregation of FUS protein is believed to play an important role in pathogenesis of these diseases. In cultured cells, FUS variants with disease-associated amino acid substitutions or short deletions affecting nuclear localization signal (NLS) and causing cytoplasmic mislocalization can be sequestered into stress granules (SGs).", "Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics", "Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis", "Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels.", "Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules.", "Our results suggest that the ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism.", "RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations.", "TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules", "In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions", "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress", "Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules", "Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules", "Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. ", "We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. ", "Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies.", "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress.", "Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics.", "Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies. .", "Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons", "However, the role of autophagy in regulation of FUS-positive stress granules (SGs) and aggregates remains unclear. ", "Although co-localized primarily in the nucleus in normal condition, FUS/TLS and PRMT1 were partially recruited to the cytoplasmic granules under oxidative stress, which were merged with stress granules (SGs) markers in SH-SY5Y cell.", "The effect of PRMT1-mediated arginine methylation on the subcellular localization, stress granules, and detergent-insoluble aggregates of FUS/TLS", "Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules", "These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.", "Here, we exploited a Drosophila model of ALS and neuronal cell lines to elucidate the role of the RNA-binding ability of FUS in regulating FUS-mediated toxicity, cytoplasmic mislocalization and incorporation into stress granules (SGs). ", "Stress granules as crucibles of ALS pathogenesis" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "http://www.ncbi.nlm.nih.gov/pubmed/24297750", "http://www.ncbi.nlm.nih.gov/pubmed/24013423", "http://www.ncbi.nlm.nih.gov/pubmed/23257289", "http://www.ncbi.nlm.nih.gov/pubmed/24312274", "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "http://www.ncbi.nlm.nih.gov/pubmed/21173160", "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "http://www.ncbi.nlm.nih.gov/pubmed/25429138", "http://www.ncbi.nlm.nih.gov/pubmed/20674093", "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "http://www.ncbi.nlm.nih.gov/pubmed/20606625", "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "http://www.ncbi.nlm.nih.gov/pubmed/22405725", "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "http://www.ncbi.nlm.nih.gov/pubmed/24336168", "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "http://www.ncbi.nlm.nih.gov/pubmed/23152885", "http://www.ncbi.nlm.nih.gov/pubmed/19765185" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0034063", "http://www.disease-ontology.org/api/metadata/DOID:332", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000690", "http://amigo.geneontology.org/amigo/term/GO:0097165", "http://amigo.geneontology.org/amigo/term/GO:0035617" ]

[ "TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration." ]

[ "yes" ]

[ "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. ", "Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGFβ signaling. ", "Thus, TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.", "As expected, transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically upregulated in MI hearts, but its phosphorylated comediator (pSmad) was significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, suggesting that downstream signaling of TGF-beta is diminished substantially in Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling resulted in the attenuation of adverse structural remodeling as assessed by echocardiography.", "Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.", "After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition.", "Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. ", "Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition.", "TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration.", "These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22513374", "http://www.ncbi.nlm.nih.gov/pubmed/12374778", "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "http://www.ncbi.nlm.nih.gov/pubmed/17322368", "http://www.ncbi.nlm.nih.gov/pubmed/19966054", "http://www.ncbi.nlm.nih.gov/pubmed/18985280", "http://www.ncbi.nlm.nih.gov/pubmed/15883211", "http://www.ncbi.nlm.nih.gov/pubmed/10198196", "http://www.ncbi.nlm.nih.gov/pubmed/16842199" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016212", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ]

[ "Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. The MAOA gene predicts happiness in women. The heritability of happiness was estimated at 22% for males and 41% in females." ]

[]

[ "inally, a systematic review performed based on existing information. Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. ", "The MAOA gene predicts happiness in women.", "Although twin studies estimate that genetic factors account for 35-50% of the variance in human happiness, knowledge of specific genes is limited.", "This investigation examines association between happiness and monoamine oxidase A (MAOA) genotype. ", "Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other ones involving severe developmental handicap. ", "The heritability of happiness was estimated at 22% for males and 41% in females. ", "Biometric studies have shown that happiness is strongly affected by genes.", "The clustering of the four different measures (quality of life in general, satisfaction with life, quality of life at present, and subjective happiness) was explained by an underlying additive genetic factor and an underlying non-additive genetic factor. ", " happiness and the environment are influenced by genetic factors and family upbringing", "The results suggest that many putative indicators of the environment are highly heritable and, indeed, that the same genes that affect the environment may affect happiness as well." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26060713", "http://www.ncbi.nlm.nih.gov/pubmed/19728071", "http://www.ncbi.nlm.nih.gov/pubmed/24690898", "http://www.ncbi.nlm.nih.gov/pubmed/23769682", "http://www.ncbi.nlm.nih.gov/pubmed/20981772", "http://www.ncbi.nlm.nih.gov/pubmed/20397744", "http://www.ncbi.nlm.nih.gov/pubmed/22885141", "http://www.ncbi.nlm.nih.gov/pubmed/19569406", "http://www.ncbi.nlm.nih.gov/pubmed/20440640" ]

[]

[]

[ "Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease" ]

[ "catechol-O-methyltransferase" ]

[ "PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. ", "Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor.", "OBJECTIVE: The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey.", "CONCLUSIONS: Opicapone behaved as long-acting COMT inhibitor that markedly increased systemic and central levodopa bioavailability. ", "BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.", "CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. ", "Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor.", "Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor.", "Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor.", "The purpose of this study was to evaluate the tolerability, pharmacokinetics (including the effect of food) and pharmacodynamics (effect on COMT activity) following single oral doses of opicapone in young healthy male volunteers. ", "AIMS: The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. ", "CONCLUSION: Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.", "Opicapone demonstrated marked and sustained inhibition of erythrocyte soluble COMT activity.", "The long duration of COMT inhibition by opicapone, however, tended to be independent from the dose taken." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24271646", "http://www.ncbi.nlm.nih.gov/pubmed/23336248", "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "http://www.ncbi.nlm.nih.gov/pubmed/24925090" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ]

[ "The rationale for purification of the soluble lysosomal proteins resides in their characteristic sugar, the mannose-6-phosphate (M6P), which allows an easy purification by affinity chromatography on immobilized M6P receptors." ]

[]

[ "Most luminal lysosomal proteins are synthesized as precursors containing mannose 6-phosphate (Man6-P) and a number of recent studies have conducted affinity purification of Man6-P containing proteins as a step toward defining the composition of the lysosome", "This chapter describes the process of production, purification, separation, and mass spectrometry identification of soluble lysosomal proteins. The rationale for purification of these proteins resides in their characteristic sugar, the mannose-6-phosphate (M6P), which allows an easy purification by affinity chromatography on immobilized M6P receptor (MPR", "ecretions of these cells were affinity purified using an affinity matrix derivatized with MPR46 and MPR300. In the protein fraction bound to the affinity matrix and eluted with mannose 6-phosphate,", "Proteins containing mannose 6-phosphate (Man6-P), a carbohydrate modification used for targeting resident soluble lysosomal proteins to the lysosome, were affinity-purified using immobilized Man6-P receptor.", ". We purified mannose 6-phosphorylated proteins by affinity chromatography", "Since lysosomal soluble proteins are characterized by the presence of mannose-6-phosphate, they were purified on an affinity support bearing mannose-6-phosphate receptor", "The most abundant lysosomal substrates of Acp2 and Acp5 were identified by Man6P affinity chromatography and mass spectrometry.", "urinary proteins were affinity purified on immobilized Man-6-P receptors,", "A number of proteomic studies have focused on lysosomal proteins, exploiting the fact that Man-6-P-containing forms can be purified by affinity chromatography on immobilized MPRs.", "In this study, we purified the Man-6-P glycoforms of proteins from human plasma by affinity chromatography on immobilized MPRs" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18977398", "http://www.ncbi.nlm.nih.gov/pubmed/16709564", "http://www.ncbi.nlm.nih.gov/pubmed/18507433", "http://www.ncbi.nlm.nih.gov/pubmed/17258946", "http://www.ncbi.nlm.nih.gov/pubmed/18370023", "http://www.ncbi.nlm.nih.gov/pubmed/16145712", "http://www.ncbi.nlm.nih.gov/pubmed/11079561", "http://www.ncbi.nlm.nih.gov/pubmed/16399764", "http://www.ncbi.nlm.nih.gov/pubmed/15789345", "http://www.ncbi.nlm.nih.gov/pubmed/19383612", "http://www.ncbi.nlm.nih.gov/pubmed/22158965" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000345", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008247", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005764", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002846" ]

[ "The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of a significant number of genes are affected in Ewing sarcoma, some of which are known to be directly or indirectly regulated by EWS/FLI. Such genes are BCL11B, NRoB1, GSTM4, NKX2.2 and p53." ]

[ "BCL11B", "NRoB1", "GSTM4", "NKX2.2", "p53" ]

[ "BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma", "EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines", "BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature", "EWS/FLI functions as an aberrant transcription factor to regulate genes that mediate the oncogenic phenotype of Ewing's sarcoma. One of these regulated genes, NR0B1, encodes a corepressor protein, and likely plays a transcriptional role in tumorigenesis", "GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance", "We recently showed that EWS/FLI regulates one of its key targets, NR0B1, through a GGAA-microsatellite in its promoter", "We found that EWS/FLI directly binds the GSTM4 promoter, and regulates GSTM4 expression through a GGAA-microsatellite in its promoter", "The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1", "We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples", "Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma", "Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor", "Neuroblastoma-Ews/Fli-1 infectant cell lines showed marked increases in p53 protein expression without transcriptional up-regulation", "We then tested the p53 response pathway and observed that the neuroblastoma parent cells responded to genotoxic stress, whereas the neuroblastoma-Ews/Fli-1 infectants did not. These results suggest that Ews/Fli-1 can directly abrogate the p53 pathway to promote tumorigenesis", "We recently showed that EWS/FLI interacts with GGAA-microsatellites to regulate some of its target genes, including NR0B1, an EWS/FLI-regulated gene that is required for the oncogenic phenotype of Ewings sarcoma.", "BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.", "The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1.", "Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "http://www.ncbi.nlm.nih.gov/pubmed/18927503", "http://www.ncbi.nlm.nih.gov/pubmed/15492248", "http://www.ncbi.nlm.nih.gov/pubmed/17114343", "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "http://www.ncbi.nlm.nih.gov/pubmed/19920188" ]

[]

[]

[ "Some archaea replicate from single origins but most archaea and all eukaryotes replicate using multiple origins.", "Multiple functional sites of origin of replication may exist in the genomes of most archaea. This has only been demonstrated recently. Two studies have shown that multiple origins of replication function in two archaeal species." ]

[ "mostly multiple", "Multiple" ]

[ "Therefore, these lines of evidence strongly suggest that the identified region is a replication origin, which is designated as oriC1. The analysis of the y component of the Z curve, i.e., MK disparity curve, suggests the presence of another replication origin corresponding to one of the peaks in the MK disparity curve at around 1,388 kb of the genom", "Our results strongly suggest that the single replication origin of M. mazei is situated at the intergenic region", "Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins.", "multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea", "Multiple orc/cdc6-associated replication origins were predicted in all of the analyzed haloarchaeal genome", "different replication origins in some archaeal genomes leave quite different patterns of strand asymmetry", "the single chromosome of Pyrobaculum calidifontis contains four replication origins", "six archaeal genomes from the genus Sulfolobus containing three origins of replication were selected", "The strong replication-biased structuring of the Sulfolobus chromosome implies that the multiple replication origins serve purposes other than simply shortening the time required for replication", "The 3 DNA replication origins of Sulfolobus acidocaldarius", "We have used a combination of genetic, biochemical, and bioinformatic approaches to map DNA replication origins in H. volcanii. Five autonomously replicating sequences were found adjacent to cdc6/orc1 genes", "the multiple replication origin paradigm has also been demonstrated within the archaeal domain of life", "multiple chromosome replication origins in Sulfolobus species has added yet another eukaryotic trait to the archaea", "We employed Z-curve analysis to identify one replication origin in the Methanocaldococcus jannaschii genome, two replication origins in the Halobacterium species NRC-1 genome and one replication origin in the Methanosarcina mazei genome.", "Archaea seem to replicate using a single origin (as do eubacteria) even though archaeal replication factors are more like those of eukaryotes", "Based on the above analysis, a model of replication of Halobacterium NRC-1 with two replication origins and two termini has been proposed.", "In addition, the potential multiple replication origins of the archaeon Sulfolobus solfataricus are suggested by the analysis based on the Z curve method", "While multiple replication origins have been observed in archaea, considerably less is known about their evolutionary processes.", "multiple orc/cdc6-associated replication origins in haloarchaeal genomes" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15197606", "http://www.ncbi.nlm.nih.gov/pubmed/20850498", "http://www.ncbi.nlm.nih.gov/pubmed/16249118", "http://www.ncbi.nlm.nih.gov/pubmed/2541880", "http://www.ncbi.nlm.nih.gov/pubmed/16321966", "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "http://www.ncbi.nlm.nih.gov/pubmed/22978470", "http://www.ncbi.nlm.nih.gov/pubmed/16980466", "http://www.ncbi.nlm.nih.gov/pubmed/11967086", "http://www.ncbi.nlm.nih.gov/pubmed/20667100", "http://www.ncbi.nlm.nih.gov/pubmed/17350933", "http://www.ncbi.nlm.nih.gov/pubmed/18922777", "http://www.ncbi.nlm.nih.gov/pubmed/14526006", "http://www.ncbi.nlm.nih.gov/pubmed/23375370", "http://www.ncbi.nlm.nih.gov/pubmed/17511521", "http://www.ncbi.nlm.nih.gov/pubmed/22942672", "http://www.ncbi.nlm.nih.gov/pubmed/15876567", "http://www.ncbi.nlm.nih.gov/pubmed/11521661", "http://www.ncbi.nlm.nih.gov/pubmed/17956224", "http://www.ncbi.nlm.nih.gov/pubmed/15337158", "http://www.ncbi.nlm.nih.gov/pubmed/21784908", "http://www.ncbi.nlm.nih.gov/pubmed/20978102", "http://www.ncbi.nlm.nih.gov/pubmed/12646230", "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "http://www.ncbi.nlm.nih.gov/pubmed/12237132", "http://www.ncbi.nlm.nih.gov/pubmed/22812406", "http://www.ncbi.nlm.nih.gov/pubmed/17392430" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006270", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020745", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018741", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001105", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051738", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003688" ]

[ "Since loss of CYLD expression can be observed in different types of human cancer, it is now well established that CYLD acts as a tumor suppressor gene. Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. CYLD expression has also been reported to be dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans." ]

[ "Brooke-Spiegler syndrome", "BSS", "Cylindromatosis", "Multiple Familial Trichoepithelioma", "MFT" ]

[ "We detected a frameshift mutation in the CYLD gene, designated 2253delG, underlying the disorder and were able to show that a single mutation can result in distinct clinical and histologic expression in familial cylindromatosis.", "Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified", "Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT", "familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck", "phenotype of familial cylindromatosis associated with an R758X nonsense mutation in the CYLD tumour suppressor gene", "We describe a family with cylindromatosis, in which affected individuals have an inherited R758X nonsense mutation of CYLD", "YLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes", "We describe a single family with affected members exhibiting either the FC or the MFT phenotypes associated with a mutation in the CYLD gene. ", "ndividuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma", "YLD is a tumor-suppressor gene mutated in the skin appendage tumors cylindromas, trichoepitheliomas, and spiradenomas. ", "In addition, we have characterized Maspin downregulation in cylindromas, trichoepitheliomas, and spiradenomas carrying functional inactivating mutations of CYLD, also providing an evidence of the correlation between impaired CYLD function and Maspin decreased expression in vivo in human tumors", "Germ‑line mutation in cylindromatosis (CYLD), a tumor suppressor gene, causes familial cylindromatosis and Brook‑Spiegler syndrome", "atients carrying heterozygous germline truncating mutations in the CYLD gene develop multiple primary hair follicle-related tumours. A highly patterned tumour, termed cylindroma, and a highly disorganized tumour, termed spiradenoma, may both develop in the same patient.", "ultiple trichoepitheliomas associated with a novel heterozygous mutation in the CYLD gene as an adjunct to the histopathological diagnosis", "ultiple trichoepitheliomas (TEs), especially in the familial setting, have been associated with germline heterozygous mutations in the CYLD gene", "We describe a 35-year-old woman with multiple facial TEs, in whom the molecular genetic analysis revealed a novel heterozygous c.1843delT mutation in the CYLD gene", "This frameshift mutation was also present in a heterozygous state in the TE tumor cells. The demonstration of a novel CYLD mutation was used as an adjunct to the histopathological diagnosis in this case", "novel germline mutation in the CYLD gene in a Slovak patient with Brooke-Spiegler syndrome", "This new germline mutation in the CYLD gene of a Slovak patient with Brooke-Spiegler syndrome extends the catalogue of known CYLD germline mutations in this condition", "Molecular biologic study of the CYLD gene performed from the peripheral blood identified a novel splice site c.2041+1 G>T mutation", "Patients with Brooke-Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q", "Mutation and loss of heterozygosity of the CYLD gene causes development of cylindromatosis, a benign tumour originating from the skin", "Our study shows that CYLD expression is dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans", "Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS", "Since loss of CYLD expression can be observed in different types of human cancer, it is now well established that CYLD acts as a tumor suppressor gene", "mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma", "we demonstrate that the expression in tumorigenic epidermal cells of a catalytically inactive form of CYLD (CYLD(C/S)) that mimics the identified mutations of cyld in human tumors and competes with the endogenous CYLD results in enhanced cell proliferation and inhibition of apoptosi", "In contrast with previous studies showing the development of benign tumors by mutations in the CYLD gene, here we provide evidence that the occurrence of mutations in the CYLD gene in tumorigenic epidermal cells (carrying previous mutations) increases the aggressiveness of carcinomas, mainly through enhancement of the expression of angiogenic factors, having therefore a key role in epidermal cancer malignancy", "By interphase cytogenetics, a (sub)clonal biallelic CYLD deletion was observed by interphase cytogenetics in 1 of 29 primary cHL, whereas signal patterns indicating decreased CYLD copy numbers were observed in a total of 10 of 29 primary cases", "mutation in the CYLD gene within a family with Brooke-Spiegler syndrome", "rooke-Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12-q13", "authors report a case of Brooke-Spiegler syndrome (BSS) with a novel germline CYLD mutation and various somatic mutations identified in the lesional tissues", "he available histopathological material included 24 trichoepitheliomas, 2 large nodular basal cell carcinomas (BCCs), 2 spiradenomas, 1 spiradenocylindroma and 1 trichoblastoma composed of large and small nodules with prominent clear cell differentiation", "To comprehensively ascertain the extent and severity of clinical features in affected individuals from 2 large families with proven heterozygous mutations in the CYLD locus and to correlate these findings with the 3 appendageal tumor predisposition syndromes (familial cylindromatosis, Brooke-Spiegler syndrome, and multiple familial trichoepitheliomas) known to be associated with such germline mutations", "In this report, we identified a novel mutation of CYLD gene in a Chinese family with MFT", "case of Brooke-Spiegler syndrome with a novel germline deep intronic mutation in the CYLD gene leading to intronic exonization, diverse somatic mutations, and unusual histology", "present a case of Brooke-Spiegler syndrome with a germline deep intronic mutation in the CYLD gene leading to intronic exonization", "A deep intronic mutation resulting in exonization and a somatic sequence mutations causing exon skipping are hitherto unreported genetic mechanisms involving the CYLD gene in patients with Brooke-Spiegler syndrome", "novel splicing mutation of the CYLD gene in a Taiwanese family with multiple familial trichoepithelioma", "Mutations in the CYLD gene, which is also the gene responsible for familial cylindromatosis, have been reported recently", "We report a novel splicing mutation (IVS12 + 1 G-->A) in the CYLD gene in a Taiwanese pedigree with MFT, and discuss new developments in treatment options", "new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity", "rooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13", "The disease gene was mapped to 16q12-13, and mutations in the CYLD gene were identified in families with BSS", "By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16922728", "http://www.ncbi.nlm.nih.gov/pubmed/23426135", "http://www.ncbi.nlm.nih.gov/pubmed/20132422", "http://www.ncbi.nlm.nih.gov/pubmed/12190880", "http://www.ncbi.nlm.nih.gov/pubmed/19730223", "http://www.ncbi.nlm.nih.gov/pubmed/18806492", "http://www.ncbi.nlm.nih.gov/pubmed/21598248", "http://www.ncbi.nlm.nih.gov/pubmed/21552290", "http://www.ncbi.nlm.nih.gov/pubmed/21389835", "http://www.ncbi.nlm.nih.gov/pubmed/21345146", "http://www.ncbi.nlm.nih.gov/pubmed/20838385", "http://www.ncbi.nlm.nih.gov/pubmed/15541090", "http://www.ncbi.nlm.nih.gov/pubmed/20972631", "http://www.ncbi.nlm.nih.gov/pubmed/20151946", "http://www.ncbi.nlm.nih.gov/pubmed/21577203", "http://www.ncbi.nlm.nih.gov/pubmed/20607853", "http://www.ncbi.nlm.nih.gov/pubmed/19917957", "http://www.ncbi.nlm.nih.gov/pubmed/17851586", "http://www.ncbi.nlm.nih.gov/pubmed/15024746", "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "http://www.ncbi.nlm.nih.gov/pubmed/22077640", "http://www.ncbi.nlm.nih.gov/pubmed/19668078", "http://www.ncbi.nlm.nih.gov/pubmed/23641715", "http://www.ncbi.nlm.nih.gov/pubmed/19076795", "http://www.ncbi.nlm.nih.gov/pubmed/23404581", "http://www.ncbi.nlm.nih.gov/pubmed/19911186", "http://www.ncbi.nlm.nih.gov/pubmed/17083363" ]

[]

[ "http://www.uniprot.org/uniprot/CYLD_BOVIN", "http://www.uniprot.org/uniprot/CYLD_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.uniprot.org/uniprot/CYLD_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010336", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/CYLD_HUMAN", "http://www.uniprot.org/uniprot/CYLD_PONAB" ]

[ "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1). Mutations of the SMN1 gene are responsible for SMA. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA). H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.\nThe molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)." ]

[ "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)" ]

[ "Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown.", "We report clinical, electrophysiology, muscle magnetic resonance imaging and histopathology findings in a four generation family with typical dominant congenital spinal muscular atrophy features, without mutations in TRPV4, and in whom linkage to other known dominant neuropathy and spinal muscular atrophy genes has been excluded. The autopsy findings in the proband, who died at 14 months of age from an unrelated illness, provided a rare opportunity to study the neuropathological basis of dominant congenital spinal muscular atrophy. There was a redu", "Recently, the common forms of spinal muscular atrophy (SMA) have been associated with mutations of the SMN and NAIP genes on chromosome 5, in the region q11.2-13.3.", "Some correlation has been established between SMN protein levels and disease course; nevertheless, the genetic basis for SMA phenotypic variability remains unclear, and it has been postulated that the loss of an additional modifying factor contributes to the severity of type I SMA", "Using comparative genomics to screen for such a factor among evolutionarily conserved sequences between mouse and human, we have identified a novel transcript, H4F5, which lies closer to SMN1 than any previously identified gene in the region.", "A multi-copy microsatellite marker that is deleted in more than 90% of type I SMA chromosomes is embedded in an intron of this gene, indicating that H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.", "A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy", "A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA).", "Thus, the failure of SMN2 to fully compensate for SMN1 and protect from SMA is due to a nucleotide exchange (C/T) that attenuates activity of an exonic enhancer.", "Autosomal recessive childhood proximal SMA is the commonest form and is due to mutations in a gene encoding a novel protein, SMN, that appears to play a critical role in RNA metabolism but has also been shown to interact with actin-binding proteins and mediators of programmed cell death.", "Mutations of the SMN1 gene are responsible for SMA.", "All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene", "Six additional patients had anterior horn cell disease but were negative for the SMN1 gene deletion. All six had exclusion features listed in the international guidelines.", "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)", "The structures of the SMN1 gene and SMN2 pseudogene, mutations distorting the SMN1 function, the structure and functions of the Smn neurotrophic protein, its role in biogenesis of small nuclear ribonucleoproteins (snRNPs), and the principles and prdblems of molecular diagnosis in SMA are described.", "SMA are caused by mutations of the survival of motor neuron gene (SMN1) leading to a reduction of the SMN protein amount.", "From a better knowledge of the genetic basis of SMA and the defects resulting from the mutations of SMN1 in cellular or animal models, several therapeutics strategies have been selected aiming at targeting SMN2, a partially functional copy of SMN1 gene which remains present in patients, or to prevent neurons from death.", "We used a homozygosity mapping and positional cloning approach in a consanguineous family of Ashkenazi Jewish origin and identified a nonsense mutation in the vaccinia-related kinase 1 gene (VRK1) as a cause of SMA-PCH", "SMN1 and SMN2 quantification was undertaken to investigate the genotype-phenotype relationship.RESULTS: Two novel point mutations were identified in exon 3 of SMN1 (p.Tyr130Cys and p.Tyr130His) in the highly conserved Tudor domain of the Smn protein.CONCLUSIONS: The genetic basis of SMA in the rare cases of compound heterozygous carriers of SMN1 deletions is complex. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19062530", "http://www.ncbi.nlm.nih.gov/pubmed/22628388", "http://www.ncbi.nlm.nih.gov/pubmed/11442327", "http://www.ncbi.nlm.nih.gov/pubmed/9731538", "http://www.ncbi.nlm.nih.gov/pubmed/12115944", "http://www.ncbi.nlm.nih.gov/pubmed/12220455", "http://www.ncbi.nlm.nih.gov/pubmed/22323744", "http://www.ncbi.nlm.nih.gov/pubmed/9073029", "http://www.ncbi.nlm.nih.gov/pubmed/10339583", "http://www.ncbi.nlm.nih.gov/pubmed/17076267", "http://www.ncbi.nlm.nih.gov/pubmed/19646678", "http://www.ncbi.nlm.nih.gov/pubmed/20225030" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009133", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009134", "http://www.disease-ontology.org/api/metadata/DOID:767", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001284" ]

[ "Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension." ]

[ "weight gain", "growth retardation", "hirsutism", "obesity", "striae", "acne", "hypertension" ]

[ "Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. The most common cause of Cushing syndrome in children and adolescents is exogenous administration of glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension", "This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD), is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome.We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24062268", "http://www.ncbi.nlm.nih.gov/pubmed/17322955" ]

[]

[]

[ "TBC1D7 was identified as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. It was demonstrated that TSC1-TSC2-TBC1D7 (TSC-TBC) is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity to negatively regulate mTORC1 activity. In agreement with this, TBC1D7 knockdown was shown to result in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions." ]

[ "TBC1D7" ]

[ "The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions. Through its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of cell growth.", "Here, we identify and biochemically characterize TBC1D7 as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. We demonstrate that the TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity.", "TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome.", "Like the other TSC-TBC components, TBC1D7 knockdown results in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22795129" ]

[]

[ "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.biosemantics.org/jochem#4266396", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031931", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ]

[ "The calcium/calmodulin-dependent protein kinase-II (CaMK-II) is inhibited by the small molecule KN-93. KN-93 is a membrane-permeant calcium/calmodulin- dependent kinase II (CaMK-II)-selective inhibitor" ]

[ "The calcium/calmodulin-dependent protein kinase-II", "CaM kinase II", "CAMK2" ]

[ "KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells.", "Knockdown of βCaMKII by lentiviral-mediated expression of shRNA prevented the synaptic inactivity-induced increase in GluA1, as did treatment with the CaM kinase inhibitor KN-93, but not the inactive analog KN-92.", "To investigate the effects of KN-93, a CaMKII selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. ", "Injection of the CaM kinase inhibitor KN-93 into pupae resulted in a reduced number of antennal lobe glial cells migrating into the neuropil to form borders around glomeruli.", "In contrast, addition of the intracellular Ca2+ chelator BAPTA-AM or the Ca2+/calmodulin-dependent (CaM) kinase inhibitor KN93 blocked reporter gene activation in response to IH.", "These increases in CPEB phosphorylation were attenuated by a specific peptide inhibitor of CaMKII and by the general CaM-kinase inhibitor KN-93.", "Alternatively, treatment with KN-93, a selective inhibitor of CaMKII activation, or adenoviral overexpression of kinase-negative CaMKII-delta(2), inhibited ATP-dependent activation of ERK1/2 but had no effect on PDBu- or PDGF-stimulated ERK1/2.", "Ca(2+)/CaM-dependent protein kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect.", "CaM kinase inhibitor KN93 on its own exhibits little toxicity up to 10 mM, as measured by release of lactate dehydrogenase (LDH) into the culture medium.", "To further elucidate the mechanism by which calcium-induced ERK activation occurs, we used the CaM-kinase inhibitor KN-93 and an inactive analog of KN-93 (KN-92).", "Hearts were pretreated with the CaM kinase inhibitor KN-93 or the inactive analog KN-92 (0.5 microM) for 10 min before clofilium exposure.", "The calmodulin-dependent protein kinase-II (CaMK-II) inhibitor KN-93 has been shown to reversibly arrest mouse and human cells in the G1 phase of the cell cycle", "NE-induced MAP kinase and cPLA2 activation was also inhibited in cells treated with a CaM kinase II inhibitor, KN-93, or with CaM kinase II antisense oligonucleotide. ", "A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells.", "CaM kinase II activation was inhibited by KN-93 pretreatment (IC(50) approximately 1 microM).", "In vitro, KN-93 potently inhibited rabbit myocardial CaM kinase activity (calculated Ki", "KN-93 also inhibited the autophosphorylation of both the alpha- and beta-subunits of CaMKII.", "CaM kinase II activation was inhibited by KN-93 pretreatment (IC(50) approximately 1 microM)", "In vitro, KN-93 potently inhibited rabbit myocardial CaM kinase activity (calculated Ki </= 2.58 microM), but the inactive analog KN-92 did not (Ki > 100 microM)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17457979", "http://www.ncbi.nlm.nih.gov/pubmed/16896952", "http://www.ncbi.nlm.nih.gov/pubmed/14749212", "http://www.ncbi.nlm.nih.gov/pubmed/9864285", "http://www.ncbi.nlm.nih.gov/pubmed/15569687", "http://www.ncbi.nlm.nih.gov/pubmed/22290426", "http://www.ncbi.nlm.nih.gov/pubmed/11827960", "http://www.ncbi.nlm.nih.gov/pubmed/11164895", "http://www.ncbi.nlm.nih.gov/pubmed/11248432", "http://www.ncbi.nlm.nih.gov/pubmed/7690557", "http://www.ncbi.nlm.nih.gov/pubmed/8939965", "http://www.ncbi.nlm.nih.gov/pubmed/21187407", "http://www.ncbi.nlm.nih.gov/pubmed/9596994", "http://www.ncbi.nlm.nih.gov/pubmed/15175389", "http://www.ncbi.nlm.nih.gov/pubmed/10712242", "http://www.ncbi.nlm.nih.gov/pubmed/1662507" ]

[]

[ "http://www.biosemantics.org/jochem#4263678", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007266" ]

[ "Chk2 splice variants have been demonstrated to exert a dominant-negative effect on wild-type Chk2 kinase activity." ]

[]

[ "Chk2 splice variants express a dominant-negative effect on the wild-type Chk2 kinase activity", "Here we evaluated the function of four Chk2 splice proteins for which mRNA splice variants were identified in human breast carcinomas. These splice variants were stably expressed as nuclear proteins. Two splice forms (Chk2Delta4 and Chk2del(2-3)) expressed kinase activity while variants Chk2Delta11 and Chk2isoI were essentially kinase inactive. Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization.", "we suggest alternative splicing as a possible novel mechanism for repression of the Chk2 wild-type function.", "Chk2 splice variants express a dominant-negative effect on the wild-type Chk2 kinase activity.", "Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization.", "Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20080130" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043549", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016301" ]

[ "PMP22 is the common gene found mutated through a duplication in CMT1A. Other genes are\nMPZ and SH3TC2" ]

[ "PMP22", "MPZ", "SH3TC2" ]

[ "Most cases of CMT are caused by mutations in PMP22,", " structural myelin protein PMP22", "Duplication of the gene encoding the peripheral myelin protein of 22 kDa (PMP22) underlies the most common inherited neuropathy, Charcot-Marie-Tooth 1A (CMT1A), a disease without a known cure.", ". Two patients showed rearrangements in the PMP22 gene, which is commonly associated with CMT1", "Many PMP22 mutants accumulate in excess in the endoplasmic reticulum (ER) and lead to the inherited neuropathies of Charcot-Marie-Tooth (CMT) disease. ", "The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A).", "In CMT1, PMP22 duplication was the most common mutation while the second gene in order of frequency was MPZ in familial and SH3TC2 in isolated cases. ", "CMT1A/PMP22 duplication", "he most frequent subtype is type 1A (CMT1A) caused by duplication in chromosome 17p12 that includes PMP22." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25522693", "http://www.ncbi.nlm.nih.gov/pubmed/25430934", "http://www.ncbi.nlm.nih.gov/pubmed/24819634", "http://www.ncbi.nlm.nih.gov/pubmed/25500726", "http://www.ncbi.nlm.nih.gov/pubmed/25400662", "http://www.ncbi.nlm.nih.gov/pubmed/25385046", "http://www.ncbi.nlm.nih.gov/pubmed/25519680", "http://www.ncbi.nlm.nih.gov/pubmed/25429913", "http://www.ncbi.nlm.nih.gov/pubmed/25150498" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10595", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002607" ]

[ "The most frequent viruses causing myocarditis are Enterovirus, Adenovirus and Coxsackie B viruses." ]

[ "Enterovirus", "Adenovirus", "Coxsackie B virus" ]

[ "Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae", "Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy.", "n our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues.", "Coxsackie B viruses (types 1 to 5) are the most frequent reported cause of acute viral myocarditis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18039618", "http://www.ncbi.nlm.nih.gov/pubmed/18277927", "http://www.ncbi.nlm.nih.gov/pubmed/2641165", "http://www.ncbi.nlm.nih.gov/pubmed/14993139", "http://www.ncbi.nlm.nih.gov/pubmed/3889351", "http://www.ncbi.nlm.nih.gov/pubmed/8199011" ]

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[]

[ "Loss-of-function mutations in genes encoding CCM1 (also known as KRIT1), CCM2 (also known as OSM and malcavernin) or CCM3 (also known as PDCD10) cause cerebral cavernous malformations (CCMs)." ]

[ "CCM1/KRIT1", "CCM2/OSM/Malcavernin", "CCM3/PDCD10" ]

[ "Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene", "we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas", "Cerebral cavernous malformation (CCM) is a disease of vascular malformations known to be caused by mutations in one of three genes: CCM1, CCM2 or CCM3", "To study the molecular genetic and clinical features of cerebral cavernous malformations (CCM) in a cohort of Spanish patients.METHODS: We analyzed the CCM1, CCM2, and CCM3 genes", "Loss-of-function mutations in genes encoding KRIT1 (also known as CCM1), CCM2 (also known as OSM and malcavernin) or PDCD10 (also known as CCM3) cause cerebral cavernous malformations (CCMs)", "Surveying genetic variants and molecular phylogeny of cerebral cavernous malformation gene, CCM3/PDCD10", "The three cerebral cavernous malformations (CCMs) genes namely CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 have been identified for which mutations cause cerebral cavernous malformations", "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1).", "Mutations in Krev1 interaction trapped gene 1 (KRIT1) cause cerebral cavernous malformation, an autosomal dominant disease featuring malformation of cerebral capillaries resulting in cerebral hemorrhage, strokes, and seizures.", "KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein.", "Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations.", "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations.", "Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations.", "These findings document a de novo germline mutation in Kritl gene that causes cerebral cavernous malformations.", "Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral cavernous malformations 1 protein (CCM1), CCM2, and CCM3.", "Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral cavernous malformations 1 protein (CCM1), CCM2, and CCM3", "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1).", "Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene.", "Loss-of-function mutations in CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations (CCMs).", "Mutations in three genes are associated with CCM. These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10).", "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1,", "Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.", "A novel CCM1 mutation associated with multiple cerebral and vertebral cavernous malformations.", "These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10).", "CCM1 is caused by a mutation in the KRIT1 gene and CCM2 is caused by a mutation in the MGC4607 gene, while the gene for CCM3 is not yet identified.", "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1).", "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1).", "KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25122144", "http://www.ncbi.nlm.nih.gov/pubmed/24287896", "http://www.ncbi.nlm.nih.gov/pubmed/20592472", "http://www.ncbi.nlm.nih.gov/pubmed/24466005", "http://www.ncbi.nlm.nih.gov/pubmed/16100539", "http://www.ncbi.nlm.nih.gov/pubmed/24481819", "http://www.ncbi.nlm.nih.gov/pubmed/12877753", "http://www.ncbi.nlm.nih.gov/pubmed/12172908", "http://www.ncbi.nlm.nih.gov/pubmed/24990152", "http://www.ncbi.nlm.nih.gov/pubmed/14697511", "http://www.ncbi.nlm.nih.gov/pubmed/24251678", "http://www.ncbi.nlm.nih.gov/pubmed/16465592", "http://www.ncbi.nlm.nih.gov/pubmed/26246098", "http://www.ncbi.nlm.nih.gov/pubmed/11310633", "http://www.ncbi.nlm.nih.gov/pubmed/25451273", "http://www.ncbi.nlm.nih.gov/pubmed/15543491", "http://www.ncbi.nlm.nih.gov/pubmed/25086949", "http://www.ncbi.nlm.nih.gov/pubmed/12140362" ]

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[]

[ "There is very large body of evidence that DITPA is a true thyroid hormone analog, largely utilized in experimental and clinical studies." ]

[ "yes" ]

[ "DITPA normalized the elevated serum T(3) and TSH when the dose reached 1 mg/kg · d and T(4) and rT(3) increased to the lower normal range.", "The identification of 3,5-diiodothyropropionic acid (DITPA) that binds to both α- and β-type TRs with relatively low affinity was unique in that this analog improves left ventricular function in heart failure as well as lowers cholesterol.", "Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size.", "Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.", "DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure", "The results suggested that DITPA can promote a healthy vasculature independently from its thyroid-related metabolic effects. ", " Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD", "Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply.", "The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/10749704", "http://www.ncbi.nlm.nih.gov/pubmed/15072976", "http://www.ncbi.nlm.nih.gov/pubmed/21658725", "http://www.ncbi.nlm.nih.gov/pubmed/19506112", "http://www.ncbi.nlm.nih.gov/pubmed/9618233", "http://www.ncbi.nlm.nih.gov/pubmed/12414442", "http://www.ncbi.nlm.nih.gov/pubmed/11040100", "http://www.ncbi.nlm.nih.gov/pubmed/9069582", "http://www.ncbi.nlm.nih.gov/pubmed/17710084", "http://www.ncbi.nlm.nih.gov/pubmed/18353884", "http://www.ncbi.nlm.nih.gov/pubmed/8353891", "http://www.ncbi.nlm.nih.gov/pubmed/16616210", "http://www.ncbi.nlm.nih.gov/pubmed/8936682", "http://www.ncbi.nlm.nih.gov/pubmed/21131480", "http://www.ncbi.nlm.nih.gov/pubmed/17612639", "http://www.ncbi.nlm.nih.gov/pubmed/10329215", "http://www.ncbi.nlm.nih.gov/pubmed/19286941", "http://www.ncbi.nlm.nih.gov/pubmed/15572044", "http://www.ncbi.nlm.nih.gov/pubmed/18030062", "http://www.ncbi.nlm.nih.gov/pubmed/10710355", "http://www.ncbi.nlm.nih.gov/pubmed/10474790", "http://www.ncbi.nlm.nih.gov/pubmed/1403782", "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "http://www.ncbi.nlm.nih.gov/pubmed/12145478", "http://www.ncbi.nlm.nih.gov/pubmed/15454853", "http://www.ncbi.nlm.nih.gov/pubmed/20080837", "http://www.ncbi.nlm.nih.gov/pubmed/12165118", "http://www.ncbi.nlm.nih.gov/pubmed/15148346", "http://www.ncbi.nlm.nih.gov/pubmed/22993035", "http://www.ncbi.nlm.nih.gov/pubmed/21215270", "http://www.ncbi.nlm.nih.gov/pubmed/20192904", "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "http://www.ncbi.nlm.nih.gov/pubmed/7828308" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.biosemantics.org/jochem#4021241", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013956" ]

[ "Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic." ]

[]

[ "She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 × 6.4 × 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension.", "We report here a case of multiloculated disseminated perineural or Tarlov cysts (TCs). ", "TCs are typically benign, asymptomatic lesions that can simply be monitored.", "Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium. ", "Perineural (Tarlov) cysts are most often found in the sacral region and are rare in the cervical spine. ", "A case of symptomatic cervical perineural (Tarlov) cyst: clinical manifestation and management.", "Tarlov cysts or spinal perineurial cysts are uncommon lesions.", "Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium.", "Symptomatic sacral perineurial (Tarlov) cysts.", "Subsequent MRI and CT myelography demonstrated the nature of the photopenic area as secondary to vertebral erosion by sacral perineurial cyst (Tarlov cyst).", "Tarlov cysts are sacral perineural cysts. This case report describes the clinical course after biopsy of a very large Tarlov cyst via laparoscopy, which was thought preoperatively to be an adnexal mass.", "Subsequent MRI and CT myelography demonstrated the nature of the photopenic area as secondary to vertebral erosion by sacral perineurial cyst (Tarlov cyst).", "A spinal MRI scan was then performed and revealed a sacral fracture which drained into an unknown perineurial cyst (Tarlov cyst).", "Tarlov or perineurial cysts are lesions of the nerve root most often found in the sacral region. Although there is agreement that asymptomatic Tarlov cysts should be followed, it is still debated whether patients with symptomatic Tarlov cysts should be treated surgically.", "Tarlov cysts (sacral perineural cysts) are nerve root cysts found most commonly in the sacral roots,", "Tarlov cysts or spinal perineurial cysts are uncommon lesions.", "Sacral perineurial (Tarlov) cysts are rare lesions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20712856", "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "http://www.ncbi.nlm.nih.gov/pubmed/21139800", "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "http://www.ncbi.nlm.nih.gov/pubmed/19110185", "http://www.ncbi.nlm.nih.gov/pubmed/11453427", "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "http://www.ncbi.nlm.nih.gov/pubmed/25216402", "http://www.ncbi.nlm.nih.gov/pubmed/20102100", "http://www.ncbi.nlm.nih.gov/pubmed/19569467", "http://www.ncbi.nlm.nih.gov/pubmed/10758434" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052958" ]

[ "\"Sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and \"dutogliptin\" are dipeptidyl peptidase-4 (DPP-4) inhibitors." ]

[ "dipeptidyl peptidase-4 (DPP-4) inhibitors" ]

[ "The present metaanalysis was designed to assess the effect of DPP-4 inhibitors on blood lipids, verifying possible differences across compounds of this class.METHODS: An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" ", "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).", "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "Testing the therapeutic equivalence of alogliptin, linagliptin, saxagliptin, sitagliptin or vildagliptin as monotherapy or in combination with metformin in patients with type 2 diabetes.", "The aim of this review is to compare the clinical pharmacokinetics of available DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin) for the purpose of identifying potential selection preferences according to individual patient variables and co-morbidities.", "The reader will gain detailed pharmacological and clinical information on alogliptin, dutogliptin and linagliptin and will learn how these DPP IV inhibitors may widen the whole drug class.", "When considered in total, data reviewed in this report suggest that the best overall balance between potency and the clinical pharmacokinetic characteristics of distribution, metabolism and elimination may be observed with linagliptin followed closely by vildagliptin, saxagliptin, sitagliptin and alogliptin.", "Currently, there are four DPP IV inhibitors available in various countries-alogliptin, sitagliptin, vildagliptin and saxagliptin (1).", "The various marketed or under developmental status, potential gliptins have been opted to build a pharmacophore model, e.g. Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237)", "Currently, there are four DPP IV inhibitors available in various countries-alogliptin, sitagliptin, vildagliptin and saxagliptin (1)", "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2)", "Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo", "Of these, two have been approved for clinical use in the United States: sitagliptin and saxagliptin", "Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes", "To investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes", "METHODS: DATA SOURCES: an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013. ", "RESEARCH DESIGN AND METHODS: An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011. ", "METHODS: We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'. ", "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237). ", "Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4.DATA SOURCES: An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. ", "Quantitative model of the relationship between dipeptidyl peptidase-4 (DPP-4) inhibition and response: meta-analysis of alogliptin, saxagliptin, sitagliptin, and vildagliptin efficacy results.", "The dipeptidyl peptidase-4 (DPP-4) inhibitors linagliptin, sitagliptin, saxagliptin, vildagliptin and alogliptin are being developed and have been approved for the treatment of type-2 diabetes. ", "The objective of this model-based meta-analysis was to describe the time course of HbA1c response after dosing with alogliptin (ALOG), saxagliptin (SAXA), sitagliptin (SITA), or vildagliptin (VILD). ", "Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin.", "The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses.", "In conclusion, BI 1356 inhibited DPP-4 more effectively than vildagliptin, sitagliptin, saxagliptin, and alogliptin and has the potential to become the first truly once-a-day DPP-4 inhibitor for the treatment of type 2 diabetes.", "Highly potent DPP-4 inhibitors have been identified by hybrid compound design based on linagliptin and alogliptin. ", "AIM: We assessed the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin, sitagliptin, saxagliptin and alogliptin to reach the haemoglobin HbA1c target of <7% in people with type 2 diabetes. ", "Whether the DPP-IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. ", "OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes. ", "Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but not saxagliptin) met the equivalence criterion when compared with one another.", "Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.", "an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013.", "An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011.", "An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013.", "Saxagliptin.", "Vildagliptin.", "an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013.", "An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011.", "An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013.", "the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website,", "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).", "Of these, two have been approved for clinical use in the United States: sitagliptin and saxagliptin. Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'.", "Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but not saxagliptin) met the equivalence criterion when compared with one another. Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.", "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2). Alogliptin was approved for use in Japan under the trade name Nesina® in April 2010 (3).", "Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin).", "An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above.", "A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted.", "Several clinical trials have studied the addition of GLP-1 receptor agonists [exenatide BID (twice daily), lixisenatide, albiglutide] or DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin) to ongoing insulin therapy or adding insulin to ongoing therapy with a GLP-1 receptor agonist (liraglutide).", "Testing the therapeutic equivalence of alogliptin, linagliptin, saxagliptin, sitagliptin or vildagliptin as monotherapy or in combination with metformin in patients with type 2 diabetes.", "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "This review summarizes the available data on drug-drug interactions reported in the literature for these five DDP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "http://www.ncbi.nlm.nih.gov/pubmed/21320267", "http://www.ncbi.nlm.nih.gov/pubmed/24320733", "http://www.ncbi.nlm.nih.gov/pubmed/22215383", "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "http://www.ncbi.nlm.nih.gov/pubmed/22686547", "http://www.ncbi.nlm.nih.gov/pubmed/23803146", "http://www.ncbi.nlm.nih.gov/pubmed/20690781", "http://www.ncbi.nlm.nih.gov/pubmed/19791828", "http://www.ncbi.nlm.nih.gov/pubmed/23837679", "http://www.ncbi.nlm.nih.gov/pubmed/23743694", "http://www.ncbi.nlm.nih.gov/pubmed/23501107", "http://www.ncbi.nlm.nih.gov/pubmed/24996141", "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "http://www.ncbi.nlm.nih.gov/pubmed/25860270", "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "http://www.ncbi.nlm.nih.gov/pubmed/22162539", "http://www.ncbi.nlm.nih.gov/pubmed/22106978", "http://www.ncbi.nlm.nih.gov/pubmed/21913883", "http://www.ncbi.nlm.nih.gov/pubmed/25687897", "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "http://www.ncbi.nlm.nih.gov/pubmed/21500969", "http://www.ncbi.nlm.nih.gov/pubmed/17100408", "http://www.ncbi.nlm.nih.gov/pubmed/23136353", "http://www.ncbi.nlm.nih.gov/pubmed/24567800", "http://www.ncbi.nlm.nih.gov/pubmed/22429011", "http://www.ncbi.nlm.nih.gov/pubmed/18223196" ]

[]

[ "http://www.biosemantics.org/jochem#4243818", "http://www.biosemantics.org/jochem#4243458", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018819", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054873", "http://www.biosemantics.org/jochem#4274679", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069476", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274679" ]

[ "The mutational status of the immunoglobulin heavy variable (IGHV) genes, defines two subsets: mutated and unmutated CLL. Unmutated CLL patients show a shorter progression-free and overall survival than mutated CLL patients." ]

[ "The mutational status of the IGHV genes." ]

[ "One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses.", "Mutational status of the immunoglobulin heavy chain variable regions (IGHVs) of CLL cells offers useful prognostic information for high-risk patients", "but time and economical costs originally prevented it from being routinely used in a clinical setting. Instead, alternative markers of IGHV status, such as zeta-associated protein (ZAP70) or messenger RNA levels are often used", "Patients with unmutated IgV(H) gene show a shorter progression-free and overall survival than patients with immunoglobulin heavy chain variable regions (IgV(H)) gene mutated" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22560084", "http://www.ncbi.nlm.nih.gov/pubmed/16083281", "http://www.ncbi.nlm.nih.gov/pubmed/23468975", "http://www.ncbi.nlm.nih.gov/pubmed/20353875", "http://www.ncbi.nlm.nih.gov/pubmed/16014569", "http://www.ncbi.nlm.nih.gov/pubmed/20090781", "http://www.ncbi.nlm.nih.gov/pubmed/17786276", "http://www.ncbi.nlm.nih.gov/pubmed/19500131", "http://www.ncbi.nlm.nih.gov/pubmed/16825496", "http://www.ncbi.nlm.nih.gov/pubmed/19127482" ]

[]

[]

[ "Yes. MammaPrint is cleared by the FDA for breast cancer recurrence." ]

[ "yes" ]

[ "Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19506735", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/18786252" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680439", "o": "MammaPrint" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2827401", "o": "http://linkedlifedata.com/resource/umls/label/A17680439" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F383737393600D", "o": "fda" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4530503539300011", "o": "fda" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017322", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017327", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326" ]

[ "Amantadine, a dopaminergic agent, has been shown to be effective for induction of recovery from disorders of consciousness. Amantadine is a commonly prescribed medication for patients with prolonged disorders of consciousness after traumatic brain injury. Amantadine accelerates the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. Higher dosing of amantadine may be considered in the setting of brain injury." ]

[ "yes" ]

[ "We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements.", "Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. ", "Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.).", "Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.", " During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. ", "Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness.", "Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. ", "According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. ", "Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. ", "Based on the preliminary data, higher dosing may be considered in the setting of brain injury.", "Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke.", "There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). ", "This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies.", "The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease.", "This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury.", "Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15759228", "http://www.ncbi.nlm.nih.gov/pubmed/19894299", "http://www.ncbi.nlm.nih.gov/pubmed/20129511", "http://www.ncbi.nlm.nih.gov/pubmed/18540467", "http://www.ncbi.nlm.nih.gov/pubmed/20658796", "http://www.ncbi.nlm.nih.gov/pubmed/22375973", "http://www.ncbi.nlm.nih.gov/pubmed/20460949", "http://www.ncbi.nlm.nih.gov/pubmed/24025054", "http://www.ncbi.nlm.nih.gov/pubmed/24025057", "http://www.ncbi.nlm.nih.gov/pubmed/24025056", "http://www.ncbi.nlm.nih.gov/pubmed/19404190", "http://www.ncbi.nlm.nih.gov/pubmed/15825541" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003244", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000547", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.biosemantics.org/jochem#4278064", "http://www.biosemantics.org/jochem#4095490" ]

[ "Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases." ]

[ "zinc" ]

[ "matrix metalloproteinase (MMP)-9", "matrix metalloproteinase-3 (MMP-3) gene ", "matrix metalloproteinases (MMPs)", "Matrix metalloproteinase-9 (MMP-9) is a secreted glycoprotein with a major role in shaping the extracellular matrix and a detailed understanding of the secretory mechanism could help identify methods to correct diseases resulting from dysregulation of secretion.", "Gelatinase B/matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) cleaves many substrates and is produced by most cell types as a zymogen", "Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix.", "Extracellular matrix metalloproteinases (MMPs) are a family of endopeptydases which recquire a zinc ion at their active site, for proteolityc activity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25360794", "http://www.ncbi.nlm.nih.gov/pubmed/24570026", "http://www.ncbi.nlm.nih.gov/pubmed/26013370", "http://www.ncbi.nlm.nih.gov/pubmed/23001203", "http://www.ncbi.nlm.nih.gov/pubmed/26087627", "http://www.ncbi.nlm.nih.gov/pubmed/26150355", "http://www.ncbi.nlm.nih.gov/pubmed/22257051" ]

[]

[]

[ "Hyperosmia is increased olfactory acuity ", "increased olfactory acuity" ]

[ "increased olfactory acuity" ]

[ "Hyperosmia is suspected in pregnancy; however, no empirical study using validated measures of olfactory function has clearly confirmed the anecdotal reports of this phenomenon.", "subjective hyperosmia is associated with primarily negative odor-related experiences.", "Hyperosmia is increased olfactory acuity" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24302690", "http://www.ncbi.nlm.nih.gov/pubmed/21250223", "http://www.ncbi.nlm.nih.gov/pubmed/23520356" ]

[]

[]

[ "Different estimates put currently the number of human long non coding RNAs between 10,000 and 20,000" ]

[ "between 10,000 and 20,000" ]

[ "The recent ENCODE (Encyclopedia of DNA Elements) study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. ", "Over 18,000 transcripts are presently annotated as lncRNA, and encompass previously annotated classes of noncoding transcripts including large intergenic noncoding RNA, antisense RNA and processed pseudogenes", "BACKGROUND: Over 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23126680", "http://www.ncbi.nlm.nih.gov/pubmed/23846593" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ]

[ "Botulism is a severe neuroparalytic disease caused by botulinum neurotoxin (BoNT), and affects humans, all warm-blooded animals, birds, and some fishes. Botulinum toxin is produced under anaerobic conditions by the bacterium Clostridium botulinum, which is the most known etiological agent of the disease, and some other clostridia, and is one of the most dangerous toxin in the world." ]

[ "Clostridium botulinum" ]

[ "Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum.", "Cattle botulism is a fatal intoxication caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D", "Botulism in horses in the USA is attributed to Clostridium botulinum types A, B or C.", "Clostridium botulinum is the etiological agent of botulism. Due to food-borne poisoning and the potential use of the extremely toxic botulinum neurotoxin (BoNT) from C. botulinum", "Botulism is a serious neuroparalytic disease caused by toxins of Clostridium botulinum. Botulinum toxin is produced under anaerobic conditions and is one of the most dangerous toxin in the world.", "Botulism is a neuroparalytic disease that can occur in all warm-blooded animals, birds, and fishes. The disease in animals is mainly caused by toxins produced by Clostridium botulinum strains belonging to group III, although outbreaks due to toxins produced by group I and II organisms have been recognized.", "Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded animals, and some fishes. The disease is caused by exposure to toxins produced by Clostridium botulinum and other botulinum toxin-producing clostridia.", "The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans.", "Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning.", "Botulism is a disease characterized by neuromuscular paralysis and is produced from botulinum neurotoxins (BoNTs) found within the Gram positive bacterium Clostridium botulinum.", "An epidemiological investigation and laboratory detection studies showed that sausage contaminated by type A Clostridium botulinum caused this outbreak of food poisoning.", "Botulism is caused by botulinum neurotoxin produced by the bacterium Clostridium botulinum.", "Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24961027", "http://www.ncbi.nlm.nih.gov/pubmed/24246230", "http://www.ncbi.nlm.nih.gov/pubmed/24206405", "http://www.ncbi.nlm.nih.gov/pubmed/24252222", "http://www.ncbi.nlm.nih.gov/pubmed/23025151", "http://www.ncbi.nlm.nih.gov/pubmed/19573697", "http://www.ncbi.nlm.nih.gov/pubmed/17458494", "http://www.ncbi.nlm.nih.gov/pubmed/20569065", "http://www.ncbi.nlm.nih.gov/pubmed/23421373", "http://www.ncbi.nlm.nih.gov/pubmed/21975066", "http://www.ncbi.nlm.nih.gov/pubmed/21130733", "http://www.ncbi.nlm.nih.gov/pubmed/15027048", "http://www.ncbi.nlm.nih.gov/pubmed/18388640", "http://www.ncbi.nlm.nih.gov/pubmed/16080379", "http://www.ncbi.nlm.nih.gov/pubmed/23971808", "http://www.ncbi.nlm.nih.gov/pubmed/23523511", "http://www.ncbi.nlm.nih.gov/pubmed/23971806", "http://www.ncbi.nlm.nih.gov/pubmed/23971804", "http://www.ncbi.nlm.nih.gov/pubmed/24253240", "http://www.ncbi.nlm.nih.gov/pubmed/24252701", "http://www.ncbi.nlm.nih.gov/pubmed/15839401", "http://www.ncbi.nlm.nih.gov/pubmed/11153358", "http://www.ncbi.nlm.nih.gov/pubmed/21747146", "http://www.ncbi.nlm.nih.gov/pubmed/24997242", "http://www.ncbi.nlm.nih.gov/pubmed/21171846", "http://www.ncbi.nlm.nih.gov/pubmed/20961439", "http://www.ncbi.nlm.nih.gov/pubmed/23239346" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11976" ]

[ "Spermidine protects against α-synuclein neurotoxicity. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human α-synuclein, which is thought to be the principal toxic trigger of Parkinson's Disease (PD). In this line, administration of spermidine rescued α-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration." ]

[ "Spermidine protects against α-synuclein neurotoxicity" ]

[ "Spermidine protects against α-synuclein neurotoxicity.", "Here, we show that administration of the naturally occurring polyamine spermidine, which declines continuously during aging in various species, alleviates a series of PD-related degenerative processes in the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, two established model systems for PD pathology. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human α-synuclein, which is thought to be the principal toxic trigger of PD. In this line, administration of spermidine rescued α-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration.", "Spermidine protects against α-synuclein neurotoxicity", "In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human α-synuclein, which is thought to be the principal toxic trigger of PD. In this line, administration of spermidine rescued α-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes", "Together with the fact that spermidine facilitates late stages of α-Syn aggregation, our data demonstrate that spermidine promotes the very early stages of protein aggregation including α-Syn misfolding and dimerization. This finding suggests that increased levels of spermidine and potentially other polyamines can initiate the disease-related process of α-Syn." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "http://www.ncbi.nlm.nih.gov/pubmed/22662273" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013095", "http://www.biosemantics.org/jochem#4275085", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275085" ]

[ "Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are major symptoms of 4H leukodystrophy." ]

[ "hypomyelination", "hypodontia", "hypogonadotropic hypogonadism" ]

[ " MRI demonstrated diffuse cerebral hypomyelination, cerebellar atrophy, and thin corpus callosum; X-ray revealed persistent milk teeth and hypoplastic crowns and roots (figure), indicative of 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism).", "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia.", "The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy.", " The five overlapping clinical phenotypes (described as distinct entities before their molecular basis was known) include: Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); Ataxia, delayed dentition, and hypomyelination (ADDH); Tremor-ataxia with central hypomyelination (TACH); Leukodystrophy with oligodontia (LO); and Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC).", "OBJECTIVE: To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism.", "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO.", "AIM: To report one patient with slowly progressive encephalopathy, ataxia, central hypomyelination, hypodontia and hypogonadotropic hypogonadism, the 4H syndrome.", "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia", "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO", "MRI demonstrated diffuse cerebral hypomyelination, cerebellar atrophy, and thin corpus callosum; X-ray revealed persistent milk teeth and hypoplastic crowns and roots (figure), indicative of 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism)", "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO", "The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy", "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24190003", "http://www.ncbi.nlm.nih.gov/pubmed/18671210", "http://www.ncbi.nlm.nih.gov/pubmed/23242285", "http://www.ncbi.nlm.nih.gov/pubmed/22855961", "http://www.ncbi.nlm.nih.gov/pubmed/21855841", "http://www.ncbi.nlm.nih.gov/pubmed/23307887", "http://www.ncbi.nlm.nih.gov/pubmed/22451160", "http://www.ncbi.nlm.nih.gov/pubmed/25339210" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10579" ]

[ "The \"matrisome\" is defined as the ensemble of extracellular matrix proteins (ECM) proteins and associated factors. The core matrisome have been defined in mammals through the analysis of whole genome sequences and comprises of ~ 300 proteins." ]

[]

[ "Over 300 ECM molecules have been defined as comprising the \"core matrisome\" in mammals through the analysis of whole genome sequences. ", "Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this \"core matrisome\" comprises ∼300 proteins. ", "we have developed a bioinformatic approach to predict the in silico \"matrisome\" defined as the ensemble of ECM proteins and associated factors. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23539364", "http://www.ncbi.nlm.nih.gov/pubmed/21937732", "http://www.ncbi.nlm.nih.gov/pubmed/22159717" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031012", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005576", "http://www.uniprot.org/uniprot/MATRX_BRSVA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005109" ]

[ "The GAGA factor is a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin. The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions. While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization.", "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. To study the contribution of transcription factors to the establishment of this specific chromatin configuration we assembled nucleosomes on the hsp26 promoter using a cell-free reconstitution system derived from fly embryos. This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) sites (Q. Lu, L.L. Wallrath, B.D. Allan, R.L. Glaser, J.T. Lis, and S.C.R. Elgin, J. Mol. Biol. Both DH sites were readily reconstituted from extract components.", "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin." ]

[ "yes" ]

[ "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin.", "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1.", "The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions", "While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization.", " These (CT)n repeats are associated with a nonhistone protein(s) in vivo and are bound by a purified Drosophila protein, the GAGA factor, in vitro.", "This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) site", "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1.", "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin.", "The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity.", "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15579691", "http://www.ncbi.nlm.nih.gov/pubmed/8474442", "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "http://www.ncbi.nlm.nih.gov/pubmed/7737124" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0034728", "http://amigo.geneontology.org/amigo/term/GO:0000786", "http://amigo.geneontology.org/amigo/term/GO:0016584", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009707" ]

[ "The plant DNA (cytosine-5)methyltransferases are classified into the families: MET, CMT, and the de novo DRM." ]

[ "MET", "CMT", "DRM" ]

[ "The topologies of the trees were overall congruent: four monophyletic groups corresponding to the four plant C5-MTase families were clearly distinguished. In addition, sequence analyses of the plant C5-MTase target recognition domain sequences were performed and phylogenetic trees were reconstructed showing that there is good conservation among but not within the plant C5-MTase families.", "To determine the inheritance of DNA methyltransferase genes and their expression patterns we examined three major DNA methyltransferase families (MET1, CMT3 and DRM) from tobacco and the progenitor species.", "The comparative investigation of transcription levels of different genes of cytosine DNA methyltransferase family MET (MET1, MET2a, MET2b, MET3) and their methylation patterns shows that there may exist some mechanisms defending the most actively transcribed gene MET1 of this family from methylation mediated silencing. In contrast to DRM2 gene we could not find any adenine methylated GATC sites in the MET1 gene.", "Using the 1kb 3' terminal DNA fragment of the mouse methyltransferase cDNA as a probe and low stringent hybridisation conditions, a new potential methyltransferase (MTase) gene family was isolated from an Arabidopsis thaliana genomic DNA library.", "The Dnmt3 family of de novo DNA methyltransferases has recently been characterized in animals. Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity.", "These results provide the first direct demonstration that DNA-METases of a higher eukaryote are encoded by a gene family.", "Here we show that Arabidopsis DNA methyltransferase2 (AtDNMT2) is localized in nucleus and associates with histone deacetylation.", "To explore possible relationships between DNA methylation level and accumulation of DNA-(cytosine-5) methyltransferase (DNMT) transcripts, the full-length coding sequences corresponding to three different DNMT families in oil palm, namely the MET, CMT, and DRM classes, have been isolated and characterized.", "In Arabidopsis a SWI2/SNF2 chromatin remodeling factor-related protein DDM1 and a cytosine methyltransferase MET1 are required for maintenance of genomic cytosine methylation.", "Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity.", "In the present study, the isolation and characterization of two distinct cDNAs that code for carrot DNA (cytosine-5)-methyltransferase (DNA-METase) are reported.", "The Arabidopsis methylase has eight of the ten conserved sequence motifs found in prokaryote cytosine-5 methyltransferases and shows 50% homology to the murine enzyme in the methyltransferase domain.", "As deduced form the DNA sequence this protein contains all conserved sequence motifs specific for the 5m cytosine MTases." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11353082", "http://www.ncbi.nlm.nih.gov/pubmed/20331964", "http://www.ncbi.nlm.nih.gov/pubmed/19132393", "http://www.ncbi.nlm.nih.gov/pubmed/21060858", "http://www.ncbi.nlm.nih.gov/pubmed/8152926", "http://www.ncbi.nlm.nih.gov/pubmed/21542302", "http://www.ncbi.nlm.nih.gov/pubmed/9680985", "http://www.ncbi.nlm.nih.gov/pubmed/10781108", "http://www.ncbi.nlm.nih.gov/pubmed/8389441", "http://www.ncbi.nlm.nih.gov/pubmed/17689048", "http://www.ncbi.nlm.nih.gov/pubmed/10845458", "http://www.ncbi.nlm.nih.gov/pubmed/18640997" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.uniprot.org/uniprot/CMT1_DICDI" ]

[ "Centromere protein A (Cenpa for mouse, CENP-A for other species) is an essential histone H3-like protein that localizes to the centromeric region of eukaryotic chromosomes, where it replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores.", "THe histone variant CENPA is preferentially located at Centromeric chromatin" ]

[ "Centromeres", "CENPA is preferentially localized in eukaryotic centromeres" ]

[ "centromere protein A (CENPA),", "Centromere activity of the alphoid YAC was suppressed at ectopic locations on the host chromosome, as indicated by the absent or reduced assembly of CENP-A and -C.", "Heterozygous and homozygous Cenpa-GFP fusion-protein mouse mutants, generated through targeted insertion of the green fluorescent protein (GFP) gene into the mouse Cenpa gene locus, show specific localized fluorescence at all the centromeres.", "Co-immunoprecipitation assay demonstrates interaction between PARP-2 and its functional homolog PARP-1, constitutive centromere proteins Cenpa and Cenpb, and spindle checkpoint protein Bub3, but not with a third constitutive centromere protein Cenpc.", "Here we investigated the interaction of this protein with, and poly(ADP-ribosyl)ation of, three constitutive centromere proteins, Cenpa, Cenpb, and Cenpc, and a spindle checkpoint protein, Bub3", "The evidence is consistent with the proposal of a critical epigenetic function for CENP-A in marking a chromosomal region for centromere formation", "CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres.", "ENPA/Cse4 assembles centromeric chromatin on diverse DNA", "constitutive kinetochore proteins such as CENPA", "A specific histone H3 variant, CENPA, replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18314594", "http://www.ncbi.nlm.nih.gov/pubmed/23439889", "http://www.ncbi.nlm.nih.gov/pubmed/23562479", "http://www.ncbi.nlm.nih.gov/pubmed/20940262", "http://www.ncbi.nlm.nih.gov/pubmed/24213134", "http://www.ncbi.nlm.nih.gov/pubmed/12906131", "http://www.ncbi.nlm.nih.gov/pubmed/21508988", "http://www.ncbi.nlm.nih.gov/pubmed/18411404", "http://www.ncbi.nlm.nih.gov/pubmed/12011073", "http://www.ncbi.nlm.nih.gov/pubmed/9465302", "http://www.ncbi.nlm.nih.gov/pubmed/16314512", "http://www.ncbi.nlm.nih.gov/pubmed/12953060", "http://www.ncbi.nlm.nih.gov/pubmed/20119530", "http://www.ncbi.nlm.nih.gov/pubmed/19778997", "http://www.ncbi.nlm.nih.gov/pubmed/12217960", "http://www.ncbi.nlm.nih.gov/pubmed/10655499", "http://www.ncbi.nlm.nih.gov/pubmed/9605877", "http://www.ncbi.nlm.nih.gov/pubmed/21888900" ]

[ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B5XB04", "o": "http://linkedlifedata.com/resource/#_423558423034001A" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_423558423034001A", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4235584230340015", "o": "Histone H3" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B9EMI5", "o": "http://linkedlifedata.com/resource/#_4239454D49350018" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4239454D49350013", "o": "Histone H3" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4239454D49350018", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/C1BY79", "o": "http://linkedlifedata.com/resource/#_4331425937390011" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4331425937390011", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43314259373900C", "o": "Histone H3" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/A5HUM4", "o": "http://linkedlifedata.com/resource/#_413548554D3400C" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_413548554D3400C", "o": "CenpA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413548554D34008", "o": "Histone H3" } ]

[ "http://www.uniprot.org/uniprot/CENPA_XENTR", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002503", "http://www.uniprot.org/uniprot/CENPA_HUMAN", "http://www.uniprot.org/uniprot/CENPA_CHICK", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/CENPA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000775", "http://www.uniprot.org/uniprot/CENPA_CRIGR", "http://www.uniprot.org/uniprot/CENPA_DANRE", "http://www.uniprot.org/uniprot/CENPA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.uniprot.org/uniprot/CENPA_MOUSE" ]

[ "The chromodomain (chromatin organizer modifier domain) is a highly conserved motif, 40-50 amino acids in length, present in a wide range of animal and plant proteins involved in chromatin organization. Chromodomain-containing proteins can be classified into boader families based, particularly, on the presence of other types of domains. Chromodomain is present in: the heterochromatin proteins HP1 alpha and HP1 beta, chromointgrases (e.g. Tf1 integrase) the chromodomain helicase DNA-binding proteins (CHD) and CHD 1-like (CHD1L), CReMM (chromatin-related mesenchymal modulator), dna methyltransferase 3 (cmt3), the chromointegrase of the LTR-retrotransposons, the Polycomb group (PcG) proteins, the mouse Polycomb homologs (Cbx2, Cbx4, Cbx6, Cbx7, Cbx8), the chromodomain Y chromosome (CDY) family of proteins and the CDY-like protein (CDYL), the histone acetyltransferases TgMYST-A and –B, MRG-1 and -15 (MORF4-Related Gene on chromosome 15), ADP/ATP translocase 1, MPP8, MSL3, NlMof, Chp1, Chriz, dMi-2, Corto, cpSRP43, KISMET, PICKLE (PKL), ScoHET1 and ScoHET2.\n" ]

[ "HP1 alpha", "CHD proteins", "Chromodomain helicase DNA-binding protein", "CReMM", "cmt3", "chromointegrases", "Polycomb group (PcG) proteins", "Cbx2", "TgMYST-A", "MRG15", "MSL3", "Swi6", "Chp1", "dMi-2", "Corto", "ScoHET1", "cpSRP43", "CDY", "chromodomain Y chromosome", "transposable elements", "like heterochromatin protein", "LHP1", "ADP/ATP translocase 1", "CDYL", "CDY-like protein", "CHD1L", "CHD1-like", "NlMof", "TIP60", "Kismet", "Chriz", "PICKLE", "PKL", "HP1 beta", "HP1 gamma", "TgMYST –B", "Cbx4", "Cbx6", "Cbx7", "Cbx8", "ScoHET2", "Cbx3", "MPP8", "MRG1" ]

[ "Chromodomain helicase DNA-binding protein 2 affects the repair of X-ray and UV-induced DNA damage.", "Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene.", "Crystal structure of the chromodomain helicase DNA-binding protein 1 (Chd1) DNA-binding domain in complex with DNA.", "Because, in plants, DNA methylation can serve as a signal for H3-lysine9-dimethylation (H3K9me2), and subsequently for non-CG-context DNA methylation, SET-domain histone methyltransferase and chromodomain dna methyltransferase 3 (cmt3) mutations were introgressed. In suvh4 suvh5 suvh6 and cmt3 mutants, H3K9me2 associated with lacO repeats is diminished, but homologous pairing persists.", "Mutations in CHD7, the gene encoding chromodomain helicase DNA binding protein 7, are present in 60-80% of individuals with the CHARGE syndrome.", "Chromodomain is present in the integrase structures of blastopia and 412 subgroup LTR-retrotransposons and may facilitate the process of non-specific integration.", "The CHARGE syndrome is a multiple congenital malformation syndrome that usually results from deletion or heterozygous loss of function mutations of the chromodomain helicase DNA-binding protein 7 (CHD7) gene at 8q12.1.", "A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients.", "CHD1 is a subfamily member of the CHD family, which possesses a chromodomain, a helicase domain, and a DNA-binding domain.", "The chromatin organizer modifier domain (chromodomain) is present in proteins that contribute to chromatin organization and mediates their binding to methylated histone H3.", "Mass spectrometric analysis revealed serine-42, a conserved amino acid in the chromodomain, as a phosphorylation site of Cbx2. Phosphorylation of the chromodomain of Cbx2 on this residue in vitro resulted in a reduced level of binding to an H3 peptide containing trimethylated lysine-9 as well as an increase in the extent of binding to an H3 peptide containing trimethylated lysine-27, suggesting that such phosphorylation changes the binding specificity of Cbx2 for modified histone H3. Phosphorylation of the chromodomain of Cbx2 may therefore serve as a molecular switch that affects the reading of the histone modification code and thereby controls epigenetic cellular memory.", "Here we identify the ATP-dependent chromatin remodeling factor chromodomain helicase DNA-binding protein 8 (CHD8) as a novel coregulator of androgen-responsive transcription.", "Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies.", "Two new chromodomain-containing proteins that associate with heterochromatin in Sciara coprophila chromosomes.", "Both proteins, ScoHET1 of 37 kDa and ScoHET2 of 44 kDa, display two chromodomain motifs that contain the conserved residues essential for the recognition of methylated histone H3 at lysine 9.", "In this study, we present a detailed histomorphologic characterization of mice containing a mutation in the chromodomain helicase DNA-binding protein 2 (Chd2).", "Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs.", "Previous studies have shown two homologous chromodomain modules in the HP1 and Polycomb proteins exhibit discriminatory binding to related methyllysine residues (embedded in ARKS motifs) of the histone H3 tail.", "In vertebrates, HP1-like chromodomains are also present in the chromodomain Y chromosome (CDY) family of proteins adjacent to a putative catalytic motif. The human genome encodes three CDY family proteins, CDY, CDYL, and CDYL2.", "The CDY chromodomain exhibits discriminatory binding to lysine-methylated ARK(S/T) motifs, whereas the CDYL2 chromodomain binds with comparable strength to multiple ARK(S/T) motifs. Interestingly, subtle amino acid changes in the CDYL chromodomain prohibit such binding interactions in vitro and in vivo.", "We assessed mRNA transcript abundance of seven genes that code for proteins with established roles in epigenetically-mediated gene silencing [transcriptional co-repressor SIN3A, DNA (cytosine-5-) methyltransferase 1, methyl CpG binding protein 2, chromodomain helicase DNA binding protein 4, histone binding protein rbbp4, histone deacetylase 1 and nuclear receptor co-repressor 2] using qRT-PCR.", "CHD7 is a member of the chromodomain helicase DNA binding domain (CHD) family of ATP-dependent chromatin remodelling enzymes.", "The cysteine-rich CXXC domains of MBD1 bound to Ring1b and the chromodomain of hPc2.", "Methylation of lysine 9 within histone H3 and the subsequent binding of the chromodomain protein heterochromatin protein 1 (HP1) are thought to initiate heterochromatin formation in vivo and to propagate a heterochromatic state lasting through several cell divisions.", "Here, we show that the SNF2-like chromodomain helicase protein CHD8 interacts with the insulator binding protein CTCF. C", "The chromodomain (CD) of the Drosophila Polycomb protein exhibits preferential binding affinity for histone H3 when trimethylated at lysine 27.", "Despite a high degree of conservation, the Cbx chromodomains display significant differences in binding preferences.", "Three-dimensional solution structures of the chromodomains of cpSRP43.", "Recently, three functionally distinct chromodomains (CDs) have been identified in cpSRP43.", "The C-terminal helical segment typically found in the nuclear chromodomains is absent in CD1.", "Critical comparison of the structures of the chromodomains of cpSRP43 with those found in nuclear chromodomain proteins revealed that the diverse protein-protein interactions mediated by the CDs appear to stem from the differences that exist in the surface charge potentials of each CD.", "Characterization and functional analysis of CReMM, a novel chromodomain helicase DNA-binding protein.", "The present study describes a newly identified protein named CReMM (chromatin-related mesenchymal modulator). The protein was studied by bioinformatic means and classified as a member of the third subfamily of chromodomain helicase DNA-binding proteins (CHD). In silico translation defined CReMM as a multiple domains protein including two chromodomains, SNF2/ATPase, helicase C domain and an A/T-DNA-binding domain (DBD).", "Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome.", "The chromodomain is 40-50 amino acids in length and is conserved in a wide range of chromatic and regulatory proteins involved in chromatin remodeling. Chromodomain-containing proteins can be classified into families based on their broader characteristics, in particular the presence of other types of domains, and which correlate with different subclasses of the chromodomains themselves.", "Here we show that the chromodomain of CMT3 can directly interact with the N-terminal tail of histone H3, but only when it is simultaneously methylated at both the H3K9 and H3K27 positions.", "In addition to the canonical MYST HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger and a chromodomain.", "Clr7 and Clr8 are required for localization of the Swi6 chromodomain protein and for histone H3 lysine 9 methylation, thereby influencing not only mating-type switching but also transcriptional silencing in all previously characterized heterochromatic regions, chromosome segregation, and meiotic recombination in the mating-type region.", "MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation.", "MRG15 is a novel chromodomain protein that is a member of a family of genes related to MORF4. MORF4 (mortality factor on chromosome 4) induces senescence in a subset of human tumor cell lines.", "Analysis of deletion mutants of MRG15 indicated that the leucine zipper at the C-terminal region of MRG15 was important for the protein associations in MAF1 and that the N-terminal chromodomain was required for the assembly of the MAF2 protein complex. Consistent with these data was the fact that a histone acetyltransferase activity associated with MRG15 was lost when the chromodomain was deleted and that both mutant MRG15 proteins failed to activate the B-myb promoter. The various mechanisms by which MRG15 could activate gene transcription are discussed.", "The chromodomain (CD) is a highly conserved motif present in a variety of animal and plant proteins, and its probable role is to assemble a variety of macromolecular complexes in chromatin.", "Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail.", "The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a beta strand, completing the beta-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain.", "The MORF4-Related Gene on chromosome 15 (MRG15) is a member of a novel family of genes originally identified in studies to reveal cell senescence-inducing factors. MRG15 contains several predicted protein motifs, including a nuclear localization signal, a helix-loop-helix region, a leucine zipper, and a chromodomain.", "Four alleles of dMi-2 mutants were further characterized in molecular nature; dMi-2(BL1) was found to have a mutation in the ATP-binding motif of the ATPase domain, dMi-2(BL7) in the core histidine of the first plant homeodomain zinc finger and dMi-2(BL12) in a conserved serine in the chromodomain.", "These analyses also suggest that the msl-3/MRG15 duplication occurred after the fungus/animal split, while an independent duplication occurred in plants. The proteins encoded by these genes have similar structures, including a putative chromodomain close to their N-terminal end and a putative leucine zipper at their C-terminus.", "CHD1 interacts with SSRP1 and depends on both its chromodomain and its ATPase/helicase-like domain for proper association with chromatin.", "Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1.", "A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain.", "A Southern blot analysis indicated that this protein, which we have named CHD-1, for chromodomain-helicase-DNA-binding protein, is present in most, if not all, mammalian species.", "Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ.", "Chromodomain helicase DNA-binding protein 4 (CHD4), the defining subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is a nucleosome-remodeling protein of the SNF2/ISWI2 family, members of which contain two chromo domains and an ATP-dependent helicase module.", "Among those proteins with >40% regulation were Macrophage Capping protein (CAPG) and Chromodomain Helicase DNA binding protein 4 (CHD4) proteins which were significantly upregulated by pp32r1 and pp32r1Y140H overexpression.", "This heterochromatin coordinates expression levels by associating with a chromodomain protein Chp1 and an antisilencing factor Epe1.", "Within NCCs, Brg1 partners with chromatin remodeler Chromodomain-helicase-DNA-binding protein 7 (Chd7) on the PlexinA2 promoter to activate PlexinA2, which encodes a receptor for semaphorin to guide NCCs into the OFT.", "Chromodomain Helicase DNA binding protein 5 (CHD5) is a tumor suppressor mapping to 1p36, a genomic region that is frequently deleted in human cancer.", "Here, we identify ENHANCED PHOTOMORPHOGENIC1 (EPP1), previously known as PICKLE (PKL), an ATP-dependent chromatin remodeling factor of the chromodomain/helicase/DNA binding family, as a repressor of photomorphogenesis in Arabidopsis thaliana.", "Chromodomain on Y-like (CDYL) is a chromodomain protein that has sequence homology to members of the enoyl CoA hydratase family.", "Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66α) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2β) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai, M. A., Walavalkar, N. M., Wang, S. Z., Zu Zhu, S., Ginder, G. D., and Williams, D. C., Jr. (2011) p66α-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.", "Sequence analysis showed that NlElp3 contains GNAT-type HAT domain and Radical SAM domain, and NlMof contains chromodomain and MOZ-SAS acetyltransferase domain.", "We examined requirements for individual domains of chromodomain helicase DNA-binding protein 4 (CHD4), a core catalytic component of NuRD complexes, as well as the NuRD subunit methyl-binding domain protein 2 (MBD2) and methylated DNA, for NuRD function in the context of tissue-specific transcription.", "OBJECTIVE: Chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) is an SNF2-like transcription factor involved in the development of human hepatocellular carcinoma (HCC).", "Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2.", "OBJECTIVE: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers.", "The chromodomain, helicase, DNA-binding protein 5 (CHD5) is a chromatin remodeling enzyme which is implicated in tumor suppression.", "The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1β with the H3-tail.", "To test this hypothesis, we performed a comprehensive molecular dynamics study in which we analyzed a crystallographically defined complex that involves the HP1 chromodomain and an H3 tail peptide.", "Whereas the molecular target of the MRG15 chromodomain (CD) has been suggested to be H3K36me(2/3), the precise molecular target of the Pf1 plant homeodomain 1 (PHD1) has remained elusive.", "Chp1, a chromodomain (CD) protein, forms the Ago1-containing RNA-induced transcriptional silencing (RITS) complex and recruits siRNA-bound RITS to methylated histone H3 lysine 9 (H3K9me) via its CD.", "In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein.", "CHD7 is a chromodomain-containing, ATP dependent helicase protein that is highly expressed in the developing ear and is required for semicircular canal development in both humans and mice.", "Moreover, the LTR retrotransposon fraction in BAC clones harboring genes is disproportionately composed of chromodomain-containing Gypsy LTR retrotransposons ('chromoviruses'), and the majority of the intact chromoviruses contain tandem chromodomain duplications.", "Stimulated by positively charged residues in the hinge region, RNA competes with methylated histone H3K9 for binding to the chromodomain of HP1(Swi6).", "CHD7 is one of the nine members of the chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling enzymes.", "Therefore, p53, ZNF237, and Chromodomain helicase DNA-binding protein 3 inhibit the function ER Ca²⁺ leak channels to regulate both ER and cytoplasmic Ca²⁺ levels and may potentially control Ca²⁺-signaling function of PS1.", "We show that chromodomain helicase DNA-binding domain 2 (Chd2), a SNF2 chromatin remodelling enzyme family member, interacts with MyoD and myogenic gene regulatory sequences to specifically mark these loci via deposition of the histone variant H3.3 prior to cell differentiation.", "Analysis of the Neurospora crassa chromodomain protein CDP-2, a component of a newly characterized HP1-containing complex, reveals a second gene-silencing mechanism and provides insights into the dynamic nature of chromatin domains that possess shared components.", "We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein.", "Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity.", "About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7).", "Owing to different polyadenylation sites and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain.", "Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex.", "Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription.", "Here, we report that chromodomain helicase DNA-binding protein 4 (CHD4) is a novel BRIT1 binding partner that regulates the HR repair process.", "Here, we report that the chromodomain-containing protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans.", "The chromodomain protein, Chromator, can be divided into two main domains, a NH(2)-terminal domain (NTD) containing the chromodomain (ChD) and a COOH-terminal domain (CTD) containing a nuclear localization signal.", "Chromodomain helicase DNA binding protein 5 (CHD5) is a potent tumor suppressor that serves as a master regulator of a tumor-suppressive network.", "By high-resolution tiling array CGH, the smallest common deletion targeted just one gene, the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1).", "Here we report direct evidence for presynaptic pairing activity intrinsic to non-PC regions, which is facilitated by a conserved chromodomain protein, MRG-1.", "The chromodomain of MPP8 recognizes the dimethylated Dnmt3aK44me2.", "Members of the chromodomain helicase DNA-binding (CHD) family of proteins are thought to regulate gene expression.", "It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1.", "To this end, we have performed mutation studies on the Drosophila HP1α chromodomain, which binds H3K9Me(2) and H3K9Me(3) with approximately equal affinities.", "We are interested in defining which elements of the chromodomain helicase DNA-binding protein 1 (Chd1) remodeler are necessary and sufficient for sliding nucleosomes.", "Chromatin remodelers are ATP-dependent machines that dynamically alter the chromatin packaging of eukaryotic genomes by assembling, sliding, and displacing nucleosomes.", "Ocular coloboma, heart malformation, choanal atresia, retardation of growth and/or development, genital hypoplasia, and ear anomalies associated with deafness (CHARGE) syndrome is a rare, usually sporadic, autosomal dominant disorder, caused by mutations within the CHD7 (chromodomain helicase DNA-binding protein 7) gene, in nearly 70% of cases.", "Here we report that the chromodomain-containing protein CDYL specifically recognizes di- and tri-methylated H3K27 (H3K27me2 and H3K27me3) and directly interacts with EZH2, the catalytic subunit of PRC2.", "Murine Chd1 (chromodomain helicase DNA-binding protein 1), a chromodomain-containing chromatin remodeling protein, is necessary for embryonic stem (ES) cell pluripotency.", "Among those genes, zinc finger helicase (ZFH), also termed chromodomain-helicase-DNA-binding protein 3 (Chd3), was one of the highly expressed transcripts in tentative cementoblasts.", "UNLABELLED: Emerging evidence implicates the chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) as a specific oncogene in human hepatocellular carcinoma (HCC).", "Here, we investigate the function of chromodomain helicase DNA binding protein 7 (chd7) during zebrafish somitogenesis.", "Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss.", "BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate.", "Because, in plants, DNA methylation can serve as a signal for H3-lysine9-dimethylation (H3K9me2), and subsequently for non-CG-context DNA methylation, SET-domain histone methyltransferase and chromodomain dna methyltransferase 3 (cmt3) mutations were introgressed.", "Previously, we have shown that the chromodomain protein Chriz and the zinc-finger protein Z4 are essentially required for the maintenance of polytene chromosome structure.", "In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males.", "RESULTS: Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation.", "Fractionation of the extract identified a single protein, chromodomain helicase DNA binding protein 1 (Chd1), capable of the remodeling activity.", "Chromodomain helicase DNA-binding protein 5 (CHD5) has been found to be a candidate tumor suppressor gene (TSG) in malignant neural tumors.", "Similarly, CenH3-GFP distribution was altered in the absence of HP1, the chromodomain protein that binds to H3K9me3.", "ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15.", "OBJECTIVE: Chromodomain helicase DNA-binding protein (CHD) is a regulator of the chromatin remodelling process.", "We determined the crystal structure of MPP8 chromodomain in complex with H3K9me3 peptide.", "On this gene the chromodomain protein HP1γ, frequently defined as a transcriptional repressor, facilitates inclusion of the alternative exons via a mechanism involving decreased RNA polymerase II elongation rate.", "Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core component of the NuRD complex and contains a nucleosome remodeling ATPase domain along with two chromodomains and two plant homeodomain (PHD) fingers.", "H3-Lys-9-Me2 interacts with the chromodomain of Swi6/HP1.", "The chromodomain (CD) of HP1 proteins specifically recognizes the methyl mark on H3 peptides, but the same extent of specificity is not observed within chromatin.", "We have performed simulations on models of chromodomain helicase DNA-binding protein 1 complexed with a variety of histone H3 modifications.", "CHARGE syndrome is an autosomal dominant multisystem disorder caused by mutation in the CHD7 gene, encoding chromodomain helicase DNA-binding protein 7. Molecular diagnostic testing for CHD7 mutation has been available in a clinical setting since 2005.", "In this work we identified Kismet, a chromodomain-containing protein of the SNF2-like family of ATPases, as a novel component of the hedgehog transcriptional repression mechanism in anterior compartment cells." ]

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"http://www.ncbi.nlm.nih.gov/pubmed/21972924", "http://www.ncbi.nlm.nih.gov/pubmed/21358630", "http://www.ncbi.nlm.nih.gov/pubmed/21224386", "http://www.ncbi.nlm.nih.gov/pubmed/11956312", "http://www.ncbi.nlm.nih.gov/pubmed/22646239", "http://www.ncbi.nlm.nih.gov/pubmed/22715096", "http://www.ncbi.nlm.nih.gov/pubmed/16339723", "http://www.ncbi.nlm.nih.gov/pubmed/21047797", "http://www.ncbi.nlm.nih.gov/pubmed/21669865", "http://www.ncbi.nlm.nih.gov/pubmed/23071553" ]

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"http://purl.uniprot.org/uniprot/B9I6F0", "o": "http://linkedlifedata.com/resource/#_42394936463000A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42394936463000B", "o": "http://linkedlifedata.com/resource/#_42394936463000A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42394936463000A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43305654453100D", "o": "Chromodomain helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C0VTE1", "o": "http://linkedlifedata.com/resource/#_43305654453100D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_43305654453100E", "o": "http://linkedlifedata.com/resource/#_43305654453100D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_43305654453100D", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4238434154330016", "o": "Chromodomain-helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B8CAT3", "o": "http://linkedlifedata.com/resource/#_4238434154330016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4238434154330017", "o": "http://linkedlifedata.com/resource/#_4238434154330016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4238434154330016", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42364B35523200E", "o": "Chromodomain helicase hrp1" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B6K5R2", "o": "http://linkedlifedata.com/resource/#_42364B35523200E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42364B35523200F", "o": "http://linkedlifedata.com/resource/#_42364B35523200E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42364B35523200E", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42384E49523400F", "o": "Chromodomain helicase (Chd1), putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B8NIR4", "o": "http://linkedlifedata.com/resource/#_42384E49523400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42384E4952340010", "o": "http://linkedlifedata.com/resource/#_42384E49523400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42384E49523400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_433147344D3400F", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C1G4M4", "o": "http://linkedlifedata.com/resource/#_433147344D3400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_433147344D340010", "o": "http://linkedlifedata.com/resource/#_433147344D3400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_433147344D3400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_44304E45343000A", "o": "Chromodomain protein, putative" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E45343000A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513759525130009", "o": "Chromodomain Y-like protein" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513759525130009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43364839453100F", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C6H9E1", "o": "http://linkedlifedata.com/resource/#_43364839453100F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4336483945310010", "o": "http://linkedlifedata.com/resource/#_43364839453100F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_43364839453100F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D0NPW7", "o": "http://linkedlifedata.com/resource/#_44304E50573700A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44304E50573700B", "o": "http://linkedlifedata.com/resource/#_44304E50573700A" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256545539009", "o": "Chromodomain-containing protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D2VTU9", "o": "http://linkedlifedata.com/resource/#_443256545539009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44325654553900A", "o": "http://linkedlifedata.com/resource/#_443256545539009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443256545539009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513458363931009", "o": "Chromodomain protein, putative" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513458363931009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513759525039009", "o": "Chromodomain Y protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q7YRP9", "o": "http://linkedlifedata.com/resource/#_513759525039009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_51375952503900A", "o": "http://linkedlifedata.com/resource/#_513759525039009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513759525039009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5139354B543500C", "o": "Y chromosomal chromodomain protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q95KT5", "o": "http://linkedlifedata.com/resource/#_5139354B543500C" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_5139354B543500D", "o": "http://linkedlifedata.com/resource/#_5139354B543500C" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_5139354B543500C", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4139543534350010", "o": "SNF2 family chromodomain-helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/A9T545", "o": "http://linkedlifedata.com/resource/#_4139543534350010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4139543534350011", "o": "http://linkedlifedata.com/resource/#_4139543534350010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4139543534350010", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_433146484235008", "o": "Chromodomain-containing protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C1FHB5", "o": "http://linkedlifedata.com/resource/#_433146484235008" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_433146484235009", "o": "http://linkedlifedata.com/resource/#_433146484235008" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_433146484235008", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4339534A48310011", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C9SJH1", "o": "http://linkedlifedata.com/resource/#_4339534A48310011" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4339534A48310012", "o": "http://linkedlifedata.com/resource/#_4339534A48310011" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4339534A48310011", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_44304E41333900A", "o": "Chromodomain protein, putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D0NA39", "o": "http://linkedlifedata.com/resource/#_44304E41333900A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44304E41333900B", "o": "http://linkedlifedata.com/resource/#_44304E41333900A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E41333900A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_45334B535A380010", "o": "Chromodomain helicase hrp1" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/E3KSZ8", "o": "http://linkedlifedata.com/resource/#_45334B535A380010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_45334B535A380011", "o": "http://linkedlifedata.com/resource/#_45334B535A380010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_45334B535A380010", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/ecName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "2.3.1.48" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "Chromodomain Y-like protein" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q6AYK9", "o": "http://linkedlifedata.com/resource/#_513641594B39009" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "CDY-like" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11683673", "o": "1811" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44325647443600A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4531465947360019", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513957544B320013", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443257314B3600A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E453935001B", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443256464734009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_423656414439009", "o": "http://purl.uniprot.org/core/Structured_Name" } ]

[ "http://www.uniprot.org/uniprot/CHD3_DROME", "http://www.uniprot.org/uniprot/CHD7_HUMAN", "http://www.uniprot.org/uniprot/CHD4_HUMAN", "http://www.uniprot.org/uniprot/CHD1_MOUSE", "http://www.uniprot.org/uniprot/CHD7_CHICK", "http://www.uniprot.org/uniprot/CHD1_HUMAN", "http://www.uniprot.org/uniprot/CDYL_RAT", "http://www.uniprot.org/uniprot/CDY2_HUMAN", "http://www.uniprot.org/uniprot/CHD8_XENTR", "http://www.uniprot.org/uniprot/CHD7_MOUSE", "http://www.uniprot.org/uniprot/CHD1L_BOVIN", "http://www.uniprot.org/uniprot/CHD9_HUMAN", "http://www.uniprot.org/uniprot/HRP3_SCHPO", "http://www.uniprot.org/uniprot/CHD8_DANRE", "http://www.uniprot.org/uniprot/CHD6_HUMAN", "http://www.uniprot.org/uniprot/CHD8_HUMAN", "http://www.uniprot.org/uniprot/CHD1L_MOUSE", "http://www.uniprot.org/uniprot/CDYL2_HUMAN", "http://www.uniprot.org/uniprot/CDYL1_HUMAN", "http://www.uniprot.org/uniprot/CHDM_DROME", "http://www.uniprot.org/uniprot/CHD9_MOUSE", "http://www.uniprot.org/uniprot/CHD1L_DANRE", "http://www.uniprot.org/uniprot/CHD3_HUMAN", "http://www.uniprot.org/uniprot/CHD2_HUMAN", "http://www.uniprot.org/uniprot/CHD3_CAEEL", "http://www.uniprot.org/uniprot/CHD1_DROME", "http://www.uniprot.org/uniprot/CHD1_BOMMO", "http://www.uniprot.org/uniprot/CHD4_MOUSE", "http://www.uniprot.org/uniprot/HRP1_SCHPO", "http://www.uniprot.org/uniprot/CDYL_MOUSE", "http://www.uniprot.org/uniprot/CHD5_HUMAN", "http://www.uniprot.org/uniprot/CHD1L_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.uniprot.org/uniprot/CHD8_MOUSE", "http://www.uniprot.org/uniprot/CHD1_CHICK", "http://www.uniprot.org/uniprot/CHD8_RAT", "http://www.uniprot.org/uniprot/CDY1_HUMAN" ]

[ "Genomicus had been developed as a database and a browser to study gene synteny in modern and ancestral genomes. It allows easy comparative genomic visualization in >150 eukaryote genomes and in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. The graphical modules of Genomicus show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and facilitate the study of the evolution of a locus through homology relationships. The Genomicus server provides access to ancestral gene orders, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets." ]

[]

[ "Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes.", "Here we present Genomicus, a new synteny browser that can represent and compare unlimited numbers of genomes in a broad phylogenetic view. In addition, Genomicus includes reconstructed ancestral gene organization, thus greatly facilitating the interpretation of the data.AVAILABILITY: Genomicus is freely available for online use at http://www.dyogen.ens.fr/genomicus while data can be downloaded at ftp://ftp.biologie.ens.fr/pub/dyogen/genomicus.", "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes. It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. We extended the Genomicus database originally dedicated to vertebrate to four new clades, including plants, non-vertebrate metazoa, protists and fungi. This visualization tool allows evolutionary phylogenomics analysis and exploration. Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships.", "Genomicus update 2015: KaryoView and MatrixView provide a genome-wide perspective to multispecies comparative genomics.", "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides access to genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants. Here we present the new features available for vertebrate genome with a focus on new graphical tools. The interface to enter the database has been improved, two pairwise genome comparison tools are now available (KaryoView and MatrixView) and the multiple genome comparison tools (PhyloView and AlignView) propose three new kinds of representation and a more intuitive menu. These new developments have been implemented for Genomicus portal dedicated to vertebrates. This allows the analysis of 68 extant animal genomes, as well as 58 ancestral reconstructed genomes. The Genomicus server also provides access to ancestral gene orders, to facilitate evolutionary and comparative genomics studies, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets.", "Genomicus: five genome browsers for comparative genomics in eukaryota.", "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes.", "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). ", "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants).", "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate,", "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in &gt;150 eukaryote genomes.", "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "http://www.ncbi.nlm.nih.gov/pubmed/25378326" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064878", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026801" ]

[ "Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile", "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone.", "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile.", "No. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile.", "Amiodarone, an iodinated benzofuran derivative, introduced in 1960 s as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970 s and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent. " ]

[ "no" ]

[ "Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone.", "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. ", "Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent.", "Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties.", "Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias.", "Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent", "Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia", "Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent", "Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile", "Amiodarone is a potent class III anti-arrhythmic drug that also possesses beta-blocking properties" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15989900", "http://www.ncbi.nlm.nih.gov/pubmed/20041841", "http://www.ncbi.nlm.nih.gov/pubmed/17352036", "http://www.ncbi.nlm.nih.gov/pubmed/21626366", "http://www.ncbi.nlm.nih.gov/pubmed/12491809", "http://www.ncbi.nlm.nih.gov/pubmed/11825323", "http://www.ncbi.nlm.nih.gov/pubmed/21728182" ]

[]

[ "http://www.biosemantics.org/jochem#4274241", "http://www.biosemantics.org/jochem#4075064" ]

[ "Delayed enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients, and is associated with cardiovascular mortality, heart failure death, and all-cause mortality in HCM." ]

[ "Delayed enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients." ]

[ " It is possible to conclude that there is a high prevalence of myocardial fibrosis in hypertrophic cardiomyopathy patients with high-risk or recovered from cardiac sudden death, like those with clinical indication to implantable cardioverter -defibrillator. ", "AF in HCM is related with myocardial fibrosis detected by DE-CMR and dilatation of the LA. ", "Over the follow-up period, the annualized adverse cardiovascular event rate in patients with DE exceeded that in patients without DE but did not achieve statistical significance (5.5% versus 3.3%; P=0.5). ", "Late gadolinium enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients. There are significant relationships between LGE and cardiovascular mortality, heart failure death, and all-cause mortality in HCM. Additionally, LGE and SCD/aborted SCD displayed a trend toward significance. ", "The hyperenhanced apical myocardium had a lower percentage of systolic myocardial thickening, and was associated with serious symptoms (e.g. syncope) and ventricular arrhythmias. ", "A semi-quantitative index of DCE is a significant multivariable predictor of both clinical VT/VF and of risk for SCD and may contribute to risk assessment in borderline or controversial cases.", "Myocardial scar imaged by CE-CMR is common in patients with HCM, and is predictive of VT. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19740409", "http://www.ncbi.nlm.nih.gov/pubmed/23376948", "http://www.ncbi.nlm.nih.gov/pubmed/22128204", "http://www.ncbi.nlm.nih.gov/pubmed/19784900", "http://www.ncbi.nlm.nih.gov/pubmed/20688032", "http://www.ncbi.nlm.nih.gov/pubmed/18204915", "http://www.ncbi.nlm.nih.gov/pubmed/22135401", "http://www.ncbi.nlm.nih.gov/pubmed/12224720", "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "http://www.ncbi.nlm.nih.gov/pubmed/18562248", "http://www.ncbi.nlm.nih.gov/pubmed/22498326", "http://www.ncbi.nlm.nih.gov/pubmed/22348519", "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "http://www.ncbi.nlm.nih.gov/pubmed/15861263", "http://www.ncbi.nlm.nih.gov/pubmed/21498307", "http://www.ncbi.nlm.nih.gov/pubmed/20339815", "http://www.ncbi.nlm.nih.gov/pubmed/19474054", "http://www.ncbi.nlm.nih.gov/pubmed/22687593", "http://www.ncbi.nlm.nih.gov/pubmed/20079992", "http://www.ncbi.nlm.nih.gov/pubmed/20667520", "http://www.ncbi.nlm.nih.gov/pubmed/20102955", "http://www.ncbi.nlm.nih.gov/pubmed/18208827", "http://www.ncbi.nlm.nih.gov/pubmed/19477402", "http://www.ncbi.nlm.nih.gov/pubmed/22935464" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.disease-ontology.org/api/metadata/DOID:11984", "http://www.disease-ontology.org/api/metadata/DOID:11986", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024741", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312" ]

[ "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. ", "COUGER is a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. It takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors. The identified co-factors are presented in a user-friendly output page, together with information that allows the user to understand and to explore the contributions of individual co-factor features." ]

[]

[ "COUGER--co-factors associated with uniquely-bound genomic regions.", "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors. The identified co-factors are presented in a user-friendly output page, together with information that allows the user to understand and to explore the contributions of individual co-factor features. COUGER can be run as a stand-alone tool or through a web interface: http://couger.oit.duke.edu.", "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs.", "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences.", "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences", "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. ", "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors.", "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24861628" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984" ]

[ "No drug therapy available today" ]

[ "No drug therapy available today" ]

[ " tick-borne encephalitis (TBE) have been detected in Bulgaria. Considering the remarkable increase in TBE morbidity in Europe over the past two decades, we conducted a study of TBE among patients with acute viral meningitis who were hospitalised in Bulgaria during 2009 to 2012. ", "Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24001228", "http://www.ncbi.nlm.nih.gov/pubmed/24076358", "http://www.ncbi.nlm.nih.gov/pubmed/24225644", "http://www.ncbi.nlm.nih.gov/pubmed/23697658", "http://www.ncbi.nlm.nih.gov/pubmed/22535622", "http://www.ncbi.nlm.nih.gov/pubmed/24035586", "http://www.ncbi.nlm.nih.gov/pubmed/23919605", "http://www.ncbi.nlm.nih.gov/pubmed/24256889", "http://www.ncbi.nlm.nih.gov/pubmed/20656033", "http://www.ncbi.nlm.nih.gov/pubmed/23452322", "http://www.ncbi.nlm.nih.gov/pubmed/22730949", "http://www.ncbi.nlm.nih.gov/pubmed/24096319", "http://www.ncbi.nlm.nih.gov/pubmed/23784447", "http://www.ncbi.nlm.nih.gov/pubmed/22727684", "http://www.ncbi.nlm.nih.gov/pubmed/23096037", "http://www.ncbi.nlm.nih.gov/pubmed/22984545", "http://www.ncbi.nlm.nih.gov/pubmed/24159517", "http://www.ncbi.nlm.nih.gov/pubmed/23377671", "http://www.ncbi.nlm.nih.gov/pubmed/23638205", "http://www.ncbi.nlm.nih.gov/pubmed/23259984" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050175", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993", "o": "Flavivirus infectious disease" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050175", "o": "tick-borne encephalitis" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060829", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018349", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004664", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004669", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017282", "http://www.disease-ontology.org/api/metadata/DOID:0050175", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004672", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004663", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004675", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004667" ]

[ "Yes, SLC22A3 (organic cation transporter (OCT3)) is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission." ]

[ "yes" ]

[ "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. ", "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters.", "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain", "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. ", "CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters.", " The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission.", "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission.", "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "http://www.ncbi.nlm.nih.gov/pubmed/18513366", "http://www.ncbi.nlm.nih.gov/pubmed/19033200", "http://www.ncbi.nlm.nih.gov/pubmed/15028779", "http://www.ncbi.nlm.nih.gov/pubmed/19702534" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0091809", "o": "D009474" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0091286", "o": "D009474" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054022" ]

[ "Yes, TIEG1 (also known as KLF10) seems to play a role in regulating apoptosis." ]

[ "yes" ]

[ "TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear", "overexpression of TIEG1, protected ALL cells against chemotherapy-induced cell death", " TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells", "We also demonstrate that TIEG-1 ectopic expression in CGNPs induces cell cycle arrest that can lead to apoptosis but fails to promote differentiation", "TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFbeta/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis.", "TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis", "the transforming growth factor-beta- (TGF-beta-) inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta-regulated cell growth control and apoptosis", "Induction of mRNA for Smad4 and the TGF-beta1-regulated apoptosis-inducing transcription factor TGF-beta1-inducible early gene (TIEG1) was detected within the first 6 h of doxazosin treatmen", "TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines", "Influence of TIEG1 on apoptosis", "the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax", "The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway", "the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-β1-resistant HCC cell lines,", "On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis", "LF10, transforming growth factor-β-inducible early gene 1", "IEG1 can induce apoptosis of cancer cells", "TGF-β inducible early gene 1) plays a significant role in regulating cell proliferation and apoptosis", "TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-β treatment", "Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1(-/-) cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1(-/-) precursors and eliminated the differentiation and apoptosis defects", "(TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types", "TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade", "(TIEG) is a family of primary response genes induced by TGF-beta, which are well recognized in regulating cellular proliferation and apoptosis", "In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth", "overexpression of TIEG1 in OLI-neu cells induced apoptosis", "(TGF-beta(1))-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis", "ectopic overexpression of TIEG is sufficient to trigger the apoptotic cell program in these cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10471833", "http://www.ncbi.nlm.nih.gov/pubmed/12771931", "http://www.ncbi.nlm.nih.gov/pubmed/10573529", "http://www.ncbi.nlm.nih.gov/pubmed/20945337", "http://www.ncbi.nlm.nih.gov/pubmed/20691807", "http://www.ncbi.nlm.nih.gov/pubmed/17659279", "http://www.ncbi.nlm.nih.gov/pubmed/12788480", "http://www.ncbi.nlm.nih.gov/pubmed/17308981", "http://www.ncbi.nlm.nih.gov/pubmed/22349513", "http://www.ncbi.nlm.nih.gov/pubmed/18930345", "http://www.ncbi.nlm.nih.gov/pubmed/17951258", "http://www.ncbi.nlm.nih.gov/pubmed/21423731", "http://www.ncbi.nlm.nih.gov/pubmed/23815903", "http://www.ncbi.nlm.nih.gov/pubmed/14743447", "http://www.ncbi.nlm.nih.gov/pubmed/22563190", "http://www.ncbi.nlm.nih.gov/pubmed/22025675", "http://www.ncbi.nlm.nih.gov/pubmed/20201061", "http://www.ncbi.nlm.nih.gov/pubmed/17729309", "http://www.ncbi.nlm.nih.gov/pubmed/23244828", "http://www.ncbi.nlm.nih.gov/pubmed/21524276", "http://www.ncbi.nlm.nih.gov/pubmed/12065093" ]

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"http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1308314", "o": "http://linkedlifedata.com/resource/umls/id/C0012940" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050767", "o": "DNA Binding Protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0404940", "o": "DNA binding protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17877761", "o": "DNA-Binding Proteins [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17974184", "o": "Binding Protein, DNA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050901", "o": "DNA-Binding Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050769", "o": "DNA Binding Proteins" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1308314", "o": "http://linkedlifedata.com/resource/umls/id/C0040648" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0057942", "o": "Factors, Transcription" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17904335", "o": "Transcription Factors [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18024172", "o": "Factor, Transcription" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0127530", "o": "Transcription Factors" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1811857", "o": "transcription factors" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18048422", "o": "Transcription Factor" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1959548", "o": "TRANSCRIPTION FACTOR" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0490726", "o": "transcription factor" } ]

[ "http://www.uniprot.org/uniprot/KLF10_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017209", "http://www.uniprot.org/uniprot/KLF10_MOUSE", "http://www.uniprot.org/uniprot/KLF10_HUMAN" ]

[ "The Opa1 protein localizes to the mitochondria.", "Opa1 is found normally in the mitochondrial intermembrane space." ]

[ "mitochondrial intermembrane space" ]

[ ". The subcellular distribution of mOPA1 overexpressed in COS-7 cells largely overlapped that of endogenous cytochrome c, a well known mitochondrial marker,", "elease of high MW Opa-1 isoforms from the mitochondria to the cytosol", " mitochondrial fusion (opa-1)", "mitochondrial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1) ", "Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. Submitochondrial fractionation by sucrose density-gradient centrifugation shows that the 88-kDa protein predominantly associates with the mitochondrial outer membrane, on the contrary, the 93-kDa protein associates with the inner membrane. ", "We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. ", "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria.", "Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage.", "Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria.", "The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space.", "In addition to the capacity of these proteins to promote fusion, mitofusin 2 or OPA1 regulate mitochondrial metabolism and loss-of-function reduces oxygen consumption and the capacity to oxidize substrates.", "Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations.", "Our experiments restrict the function of prohibitins to mitochondria and identify the processing of the dynamin-like GTPase OPA1, an essential component of the mitochondrial fusion machinery, as the central cellular process controlled by prohibitins.", "LRRK2 partially co-localizes with endosomal dynamin-1 or with mitofusins and OPA1 at mitochondrial membranes.", "While initial fusion of mitochondria by 15d-PGJ2 required the presence of both outer (Mfn1 and Mfn2) and inner (OPA1) mitochondrial membrane fusion proteins, later mitochondrial changes involved increased degradation of the fusion protein OPA1 and ubiquitination of newly synthesized OPA1 along with decreased expression of Mfn1 and Mfn2, which likely contributed to the loss of tubular rigidity, disorganization of cristae, and formation of large swollen degenerated dysfunctional mitochondria.", "Assay and properties of the mitochondrial dynamin related protein Opa1.", "Mitochondrial remodeling following fission inhibition by 15d-PGJ2 involves molecular changes in mitochondrial fusion protein OPA1.", "We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial Ca(2+) signaling and aldosterone production in H295R adrenocortical cells.", "Our results define, for the first time, a function of the middle domain of the Opa1 protein and demonstrate that mitochondrial retention of Opa1 protein is essential for normal embryogenesis.", "Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations", "Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria", "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria. ", "Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence.", "The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. ", "Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, indicating an inability to fuse. ", "Opa1, also known as Mgm1 in yeast, is a mitochondrial member of the dynamin family.", "Unlike other dynamin family members, Opa1 has an N-terminal mitochondrial targeting sequence, suggesting that this protein is imported into mitochondria.", "Here, we describe biochemical techniques, such as mitochondrial isolation, digitonin extraction, a protease protection assay, and carbonate extraction, that were used to determine that mammalian Opa1 resides in the intermembrane space where it is tightly bound to the inner membrane.", "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space,", "The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles.", "we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations.", "PKA phosphorylates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual-specificity A-kinase anchoring protein associated with lipid droplets.", "We find that Mgm1/OPA1 is localized to the mitochondrial intermembrane space," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23906536", "http://www.ncbi.nlm.nih.gov/pubmed/19168126", "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "http://www.ncbi.nlm.nih.gov/pubmed/22406748", "http://www.ncbi.nlm.nih.gov/pubmed/18281461", "http://www.ncbi.nlm.nih.gov/pubmed/22579715", "http://www.ncbi.nlm.nih.gov/pubmed/21983901", "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "http://www.ncbi.nlm.nih.gov/pubmed/17545159", "http://www.ncbi.nlm.nih.gov/pubmed/11847212", "http://www.ncbi.nlm.nih.gov/pubmed/25298396", "http://www.ncbi.nlm.nih.gov/pubmed/25744979", "http://www.ncbi.nlm.nih.gov/pubmed/20045077", "http://www.ncbi.nlm.nih.gov/pubmed/23663851", "http://www.ncbi.nlm.nih.gov/pubmed/20079867", "http://www.ncbi.nlm.nih.gov/pubmed/21980395", "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "http://www.ncbi.nlm.nih.gov/pubmed/25112877", "http://www.ncbi.nlm.nih.gov/pubmed/14970223", "http://www.ncbi.nlm.nih.gov/pubmed/12123827", "http://www.ncbi.nlm.nih.gov/pubmed/24632637", "http://www.ncbi.nlm.nih.gov/pubmed/18074630", "http://www.ncbi.nlm.nih.gov/pubmed/25582749", "http://www.ncbi.nlm.nih.gov/pubmed/25847151", "http://www.ncbi.nlm.nih.gov/pubmed/20678484", "http://www.ncbi.nlm.nih.gov/pubmed/25579226", "http://www.ncbi.nlm.nih.gov/pubmed/24633199", "http://www.ncbi.nlm.nih.gov/pubmed/24282027", "http://www.ncbi.nlm.nih.gov/pubmed/16737747", "http://www.ncbi.nlm.nih.gov/pubmed/21459773", "http://www.ncbi.nlm.nih.gov/pubmed/11017079", "http://www.ncbi.nlm.nih.gov/pubmed/21397211", "http://www.ncbi.nlm.nih.gov/pubmed/20652258" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0070585" ]

[ "Dopaminergic drugs should be given in patients with BMS. \nCatuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease.\nCapsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS.\nTreatment with placebos produced a response that was 72% as large as the response to active drugs" ]

[ "Dopaminergig drugs", "Catuama", "Capsaicina", "Alpha-lipoic acid", "Clonazepam", "Placebo therapy" ]

[ "On average, treatment with placebos produced a response that was 72% as large as the response to active drugs.", "The concomitant prescription of tongue protector and AV is effective for treating patients with BMS.", "We suggest that a subset of patients with BMS may be a phenotypic variant of RLS and a trial of dopaminergic drugs should be given in patients with BMS who has a history suggestive of RLS or in a patient who do not show a response to usual therapies for BMS.", "The systemic administration of Catuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease.", "Therapies that used capsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS.", "Topical clonazepam, which previous analyses of clinical evidence have shown to be the drug of choice for BMS, also proved to be the most cost-effective of the drugs analysed for this condition." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8725589", "http://www.ncbi.nlm.nih.gov/pubmed/22669143", "http://www.ncbi.nlm.nih.gov/pubmed/18976257", "http://www.ncbi.nlm.nih.gov/pubmed/1776404", "http://www.ncbi.nlm.nih.gov/pubmed/17287703", "http://www.ncbi.nlm.nih.gov/pubmed/22040716", "http://www.ncbi.nlm.nih.gov/pubmed/20690412", "http://www.ncbi.nlm.nih.gov/pubmed/12536654", "http://www.ncbi.nlm.nih.gov/pubmed/1923398", "http://www.ncbi.nlm.nih.gov/pubmed/22957483", "http://www.ncbi.nlm.nih.gov/pubmed/14650993", "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/2726203", "http://www.ncbi.nlm.nih.gov/pubmed/24558551", "http://www.ncbi.nlm.nih.gov/pubmed/22819057", "http://www.ncbi.nlm.nih.gov/pubmed/23229252", "http://www.ncbi.nlm.nih.gov/pubmed/1508523", "http://www.ncbi.nlm.nih.gov/pubmed/17541900", "http://www.ncbi.nlm.nih.gov/pubmed/23429751", "http://www.ncbi.nlm.nih.gov/pubmed/17559486", "http://www.ncbi.nlm.nih.gov/pubmed/18548844", "http://www.ncbi.nlm.nih.gov/pubmed/10625850", "http://www.ncbi.nlm.nih.gov/pubmed/9830647", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/20415927", "http://www.ncbi.nlm.nih.gov/pubmed/22092585", "http://www.ncbi.nlm.nih.gov/pubmed/15210564", "http://www.ncbi.nlm.nih.gov/pubmed/19837207", "http://www.ncbi.nlm.nih.gov/pubmed/22260804", "http://www.ncbi.nlm.nih.gov/pubmed/18588600", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/18343329", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/19450321", "http://www.ncbi.nlm.nih.gov/pubmed/22612823", "http://www.ncbi.nlm.nih.gov/pubmed/12110042", "http://www.ncbi.nlm.nih.gov/pubmed/2811814", "http://www.ncbi.nlm.nih.gov/pubmed/8543701", "http://www.ncbi.nlm.nih.gov/pubmed/21223496", "http://www.ncbi.nlm.nih.gov/pubmed/21743415", "http://www.ncbi.nlm.nih.gov/pubmed/20969436", "http://www.ncbi.nlm.nih.gov/pubmed/21743413", "http://www.ncbi.nlm.nih.gov/pubmed/22750263", "http://www.ncbi.nlm.nih.gov/pubmed/16903201", "http://www.ncbi.nlm.nih.gov/pubmed/20597947", "http://www.ncbi.nlm.nih.gov/pubmed/24164777", "http://www.ncbi.nlm.nih.gov/pubmed/11441716", "http://www.ncbi.nlm.nih.gov/pubmed/21528119", "http://www.ncbi.nlm.nih.gov/pubmed/14704612", "http://www.ncbi.nlm.nih.gov/pubmed/11838624", "http://www.ncbi.nlm.nih.gov/pubmed/19658340", "http://www.ncbi.nlm.nih.gov/pubmed/22044166", "http://www.ncbi.nlm.nih.gov/pubmed/18558051", "http://www.ncbi.nlm.nih.gov/pubmed/22344742", "http://www.ncbi.nlm.nih.gov/pubmed/2098940", "http://www.ncbi.nlm.nih.gov/pubmed/19689438", "http://www.ncbi.nlm.nih.gov/pubmed/15195716", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/11485137", "http://www.ncbi.nlm.nih.gov/pubmed/10425973", "http://www.ncbi.nlm.nih.gov/pubmed/16637799", "http://www.ncbi.nlm.nih.gov/pubmed/14765022", "http://www.ncbi.nlm.nih.gov/pubmed/7629360", "http://www.ncbi.nlm.nih.gov/pubmed/8323246", "http://www.ncbi.nlm.nih.gov/pubmed/9844361" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009059", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009055" ]

[ "The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%." ]

[ "yes" ]

[ "Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%", "The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly", "Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC)", "A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C", "Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC).", "The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors.", "These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis", "Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors", "Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors", "The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype)", "The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11297621", "http://www.ncbi.nlm.nih.gov/pubmed/16487009", "http://www.ncbi.nlm.nih.gov/pubmed/9832031", "http://www.ncbi.nlm.nih.gov/pubmed/21417916", "http://www.ncbi.nlm.nih.gov/pubmed/12203792", "http://www.ncbi.nlm.nih.gov/pubmed/18055323", "http://www.ncbi.nlm.nih.gov/pubmed/9790504" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3962", "http://www.uniprot.org/uniprot/PTEN_XENLA" ]

[ "The Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution." ]

[ "GBshape" ]

[ "GBshape: a genome browser database for DNA shape annotations.", "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.", "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. ", "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.", "Whereas higher-order effects, such as chromatin accessibility, cooperativity and cofactors, have been described, DNA shape recently gained attention as another feature that fine-tunes the DNA binding specificities of some transcription factor families. Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework.", "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25326329" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064878", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ]

[ "There have been a few case reports to suggest that ceftriaxone can be effective for treatment of amyotrophic lateral sclerosis. However, other case reports did not report clinical benefit of ceftriaxone therapy for ALS. Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis a through increased expression and activity of the glutamate transporter, GLT1. Clinical trials investigating potential clinical benefits of ceftriaxone in ALS are ongoing." ]

[]

[ "Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis. ", "Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1).", "OBJECTIVES: Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. ", "Thirty-four compounds (including riluzole, ceftriaxone, minocyclin, PBA, lithium, acetylcysteine) in human and mouse ALS trials and an additional set of 1040 FDA-approved compounds also showed no effect on SOD1 promoter activity. ", "Two of these patients received ceftriaxone for 1 month without clinical improvement.", "In amyotrophic lateral sclerosis, down-regulation of the astrocyte-specific glutamate excitatory amino acid transporter 2 is hypothesized to increase extracellular glutamate, thereby leading to excitotoxic motor neuron death. The antibiotic ceftriaxone was recently reported to induce excitatory amino acid transporter 2 and to prolong the survival of mutant superoxide dismutase 1 transgenic mice.", "OBJECTIVE: Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis and in an in-vitro model of neuronal ischaemia through increased expression and activity of the glutamate transporter, GLT1. ", "Dysfunction of EAAT2 is implicated in acute and chronic neurological disorders, including stroke/ischemia, temporal lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human immunodeficiency virus 1-associated dementia, and growth of malignant gliomas. Ceftriaxone, one of the beta-lactam antibiotics, is a stimulator of EAAT2 expression with neuroprotective effects in both in vitro and in vivo models based in part on its ability to inhibit neuronal cell death by glutamate excitotoxicity. ", "Motor neuron disease recovery associated with IV ceftriaxone and anti-Babesia therapy.", "This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine.", "Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS.", "Ongoing trials are exploring the value of antiglutamatergic agents, including the cephalosporin antibiotic ceftriaxone, as well as antioxidants, mitochondrial enhancers and anti-apoptotic drugs. ", "Recently, Rothstein et al. reported that beta-lactam antibiotics, including penicillin and ceftriaxone, are potential therapeutic drugs to treat some neurological disorders, e.g., amyotrophic lateral sclerosis (ALS), by modulating the expression of glutamate transporter GLT1 via gene activation. ", "Ceftriaxone was neuroprotective in vitro when used in models of ischaemic injury and motor neuron degeneration, both based in part on glutamate toxicity. When used in an animal model of the fatal disease ALS, the drug delayed loss of neurons and muscle strength, and increased mouse survival. ", "We describe two patients with lateral amyotrophic sclerosis who, after informed consent, received empirical treatment with intravenous cephtriaxone at a dose of 2 g/24 hours for three weeks, with no positive results.", "Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy.", " Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis.", "The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19008722", "http://www.ncbi.nlm.nih.gov/pubmed/20638444", "http://www.ncbi.nlm.nih.gov/pubmed/22680643", "http://www.ncbi.nlm.nih.gov/pubmed/15635412", "http://www.ncbi.nlm.nih.gov/pubmed/25297012", "http://www.ncbi.nlm.nih.gov/pubmed/19697382", "http://www.ncbi.nlm.nih.gov/pubmed/16723044", "http://www.ncbi.nlm.nih.gov/pubmed/18326497", "http://www.ncbi.nlm.nih.gov/pubmed/24771634", "http://www.ncbi.nlm.nih.gov/pubmed/19694903", "http://www.ncbi.nlm.nih.gov/pubmed/16832072", "http://www.ncbi.nlm.nih.gov/pubmed/21970974", "http://www.ncbi.nlm.nih.gov/pubmed/23613806", "http://www.ncbi.nlm.nih.gov/pubmed/8161465", "http://www.ncbi.nlm.nih.gov/pubmed/15907788", "http://www.ncbi.nlm.nih.gov/pubmed/17212618" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:332", "http://www.biosemantics.org/jochem#4249031" ]

[ "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone." ]

[]

[ "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone. ", "A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment.", "Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. ", "Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.", "479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial.", "To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score, the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer, a randomized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ (IDFS-DCIS) survival in women with node-negative, estrogen-receptor-positive breast cancer with a recurrence score of 11-25.", "One of these tests, Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome.", "We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx", "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone", "Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis", "Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs. We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx.", "479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.", "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+)," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "http://www.ncbi.nlm.nih.gov/pubmed/20665886", "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "http://www.ncbi.nlm.nih.gov/pubmed/23643806" ]

[]

[]

[ "YES" ]

[ "yes" ]

[ "The results of the present study in a unique experimental human model of maximal exposure to altitude and physical exercise demonstrate that extreme HA and strenuous physical exercise are coupled with specific endocrine adaptations. These include increased activity of the GH/IGF-I axis and a low T(3) syndrome", "3,5,3'-triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in TSH during the following 4-5 days, is seen.", "the obtained results indicate that in intense exercise, causing the rapid development of fatigue, rapid increases in serum levels of hormones of the pituitary-adrenocortical, pituitary-gonadal and pituitary-thyroid systems occur.", "Mean levels of fasting plasma estradiol, luteinizing hormone, follicle-stimulating hormone, free thyroxine and triiodothyronine were significantly lower in AR compared to ER and SE.", "Reductions in plasma T4, T3 and T3/T4 ratio are probably due to inhibition of T4 secretion and 5'-monodeiodination with possible conversion of T4 to reverse T3 (rT3). These processes may represent a mechanism for regulation of thyroid hormone metabolism during strenuous and extended flight.", "Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training.", "brief strenuous swimming or moderate bicycle exercise had minor or no effect on thyroid hormone concentrations when consideration was given to the attendant hemoconcentration.", "thyroxine were determined in 26 men participating in a 90-km cross-country ski race, before, immediately after, and on the following days", "Total thyroxine and free thyroxine in serum were significantly increased at the end of the race, but had returned to the pre-raced levels during the rest of the observation period.", "There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/3101339", "http://www.ncbi.nlm.nih.gov/pubmed/7198038", "http://www.ncbi.nlm.nih.gov/pubmed/8743723", "http://www.ncbi.nlm.nih.gov/pubmed/14637241", "http://www.ncbi.nlm.nih.gov/pubmed/16175495", "http://www.ncbi.nlm.nih.gov/pubmed/18057380", "http://www.ncbi.nlm.nih.gov/pubmed/2807143", "http://www.ncbi.nlm.nih.gov/pubmed/8325717", "http://www.ncbi.nlm.nih.gov/pubmed/596247" ]

[]

[ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.biosemantics.org/jochem#4275394", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.biosemantics.org/jochem#4275389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000609", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THA_PIG", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042404", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030375", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070460", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042403", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0097066", "http://www.biosemantics.org/jochem#4250045", "http://www.biosemantics.org/jochem#4250044", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ]

[ "Natural RNA circles function as efficient microRNA sponges. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants.", "Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. Natural RNA sponges sequestering cellular noncoding RNA molecules have been found in diverse organisms. In this issue, Lalaouna et al. (2015) report another type of RNA sponge, showing that stable intermediates of bacterial tRNA processing control endogenous small RNAs. Furthermore, survival analysis suggests that high OCT4-pg4 level is significantly correlated with poor prognosis of HCC patients." ]

[]

[ "Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma", "Mechanistic analysis revealed that OCT4-pg4 functions as a natural micro RNA sponge to protect OCT4 transcript from being inhibited by miR-145.", "Natural RNA circles function as efficient microRNA sponges", "Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants.", "Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ", "We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ", "Natural RNA sponges sequestering cellular noncoding RNA molecules have been found in diverse organisms.", "n this issue, Lalaouna et al. (2015) report another type of RNA sponge, showing that stable intermediates of bacterial tRNA processing control endogenous small RNAs.", "Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges", "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression", "This can involve RNA sponges that sequester regulatory RNAs of mRNAs in the same regulon, but the underlying molecular mechanism of such mRNA cross talk remains little understood. Here, we report sponge-mediated mRNA cross talk in the posttranscriptional network of GcvB, a conserved Hfq-dependent small RNA with one of the largest regulons known in bacteria. We show that mRNA decay from the gltIJKL locus encoding an amino acid ABC transporter generates a stable fragment (SroC) that base-pairs with GcvB. ", "the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "http://www.ncbi.nlm.nih.gov/pubmed/25630703", "http://www.ncbi.nlm.nih.gov/pubmed/25957803", "http://www.ncbi.nlm.nih.gov/pubmed/23615404", "http://www.ncbi.nlm.nih.gov/pubmed/25483404", "http://www.ncbi.nlm.nih.gov/pubmed/25404635" ]

[]

[]

[ "In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus.\nWe conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order." ]

[ "yes" ]

[ "Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men.", "We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. ", "In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. ", " The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. ", "The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. ", "MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.", "Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment.", "Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia.", "In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males.", "In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). D", "Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD.", "We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined.", "Given that DNA methylation is linked to the regulation of gene expression, we hypothesized that epigenetic mechanisms factor into the MAOA expression", " the extended MAOA regulatory region contains two CpG islands (CGIs), one of which overlaps with the canonical MAOA promoter and the other is located further upstream; both CGIs exhibit sensitivity to differential methylation.", "Identification and characterization of putative methylation targets in the MAOA locus using bioinformatic approaches.", "DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. ", "MAOA methylation is associated with nicotine and alcohol dependence in women.", "In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. ", "We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.", "Analysis of CpG methylation in the MAOA promoter region revealed substantial methylation in females but not in males.", "Therefore, allelic mRNA expression is affected by genetic and epigenetic events, both with the potential to modulate biogenic amine tone in the CNS." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22948232", "http://www.ncbi.nlm.nih.gov/pubmed/20505345", "http://www.ncbi.nlm.nih.gov/pubmed/22198720", "http://www.ncbi.nlm.nih.gov/pubmed/16893905", "http://www.ncbi.nlm.nih.gov/pubmed/22436428", "http://www.ncbi.nlm.nih.gov/pubmed/22139575", "http://www.ncbi.nlm.nih.gov/pubmed/22906985", "http://www.ncbi.nlm.nih.gov/pubmed/19777560", "http://www.ncbi.nlm.nih.gov/pubmed/18454435", "http://www.ncbi.nlm.nih.gov/pubmed/23116433", "http://www.ncbi.nlm.nih.gov/pubmed/20421737" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.uniprot.org/uniprot/AOFA_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006306", "http://www.uniprot.org/uniprot/AOFA_PONAB", "http://www.uniprot.org/uniprot/AOFA_SHEEP", "http://www.uniprot.org/uniprot/AOFA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175" ]

[ "PLN mutation R14del [or c.40_42delAGA(p.Arg14del)] was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Another PLN mutation is a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), and it was identified in two families with hereditary heart failure. Hereditary mutants of phospholamban, such as Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, cause lethal, hereditary dilated cardiomyopathy.in specific, two patients presented a G-T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution at codon 9 (R9L).One patient presented a G-A missense mutation at the same nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death." ]

[ "c.40_42delAGA(p.Arg14del)", "PLN R14 del", "PLN L39stop", "PLN R39X", "Arg(9) to Cys", "R9C", "Arg(9) to Leu", "R9L", "Arg(9) to His", "R9H" ]

[ " In 19 of 142 patients (13%), the PLN founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities.", "Recently, we showed that the c.40_42delAGA (p.Arg14del) mutation in the phospholamban (PLN) gene can be identified in 10-15 % of Dutch patients with dilated cardiomyopathy or arrhythmogenic cardiomyopathy.", "PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. ", "The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC. R14del+ patients diagnosed with DCM showed an arrhythmogenic phenotype, and SCD at young age can be the presenting symptom. These findings support the concept of 'arrhythmogenic cardiomyopathy'.", "Herein we reveal mechanistic insight into how four hereditary mutants of phospholamban, Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, and Arg(14) deletion, alter regulation of SERCA. Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates phospholamban phosphorylation and results in constitutive SERCA inhibition. Mutation of Arg(9) causes more complex changes in function, where hydrophobic substitutions such as cysteine and leucine eliminate both SERCA inhibition and phospholamban phosphorylation, whereas an aromatic substitution such as histidine selectively disrupts phosphorylation. We demonstrate that the role of Arg(9) in phospholamban function is multifaceted: it is important for inhibition of SERCA, it increases the efficiency of phosphorylation, and it is critical for protein kinase A recognition in the context of the phospholamban pentamer. Given the synergistic consequences on contractility, it is not surprising that the mutants cause lethal, hereditary dilated cardiomyopathy.", "Phospholamban (PLN) is a key regulator of SR and cardiac function, and PLN mutations in humans have been associated with dilated cardiomyopathy (DCM). We previously reported the deletion of the highly conserved amino acid residue arginine 14 (nucleic acids 39, 40 and 41) in DCM patients.", "To assess the function of this mutant PLN, we introduced the PLN-R14Del in cardiac myocytes of the PLN null mouse.", "Thus, human PLN-R14Del is misrouted to the sarcolemma, in the absence of endogenous PLN, and alters NKA activity, leading to cardiac remodeling.", "Mutations in the gene encoding PLN have been associated with idiopathic dilated cardiomyopathy; however, no systematic search for PLN mutations in heart failure has been conducted.", "Two patients presented a G-T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution at codon 9 (R9L).", "One patient presented a G-A missense mutation at the same nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). The fourth affected patient presented a T-G nonsense mutation at the nucleotide 116, substituting a termination codon for Leu-39 (L39stop).", "The genetic analysis was focused on R9C mutation with the ability to block PLN phosphorylation leading to chronic inhibition of SERCA2a activity. Another analysed mutation causing the alteration of PLN level in cells was related to the substitution of a leucine residue at position 39 with a premature stop codon (L39X). ", "A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death. ", "These effects are enhanced under oxidizing conditions, suggesting that oxidative stress may exacerbate the cardiotoxic effects of the PLN(R9C) mutant. ", "We identified 1 family with a deletion of arginine 14 in the PLN. Interestingly, unlike other individuals reported with the identical PLN mutation, these individuals were not diagnosed with dilated cardiomyopathy until their seventh decade when they were only mildly symptomatic with congestive heart failure. ", "Phospholamban R14 deletion results in late-onset, mild, hereditary dilated cardiomyopathy.", "Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phospholamban (PLN) gene in a large family with hereditary heart failure. No homozygous individuals were identified. By middle age, heterozygous individuals developed left ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias, with overt heart failure in some cases.", "Transgenic mice overexpressing the mutant PLN-R14Del recapitulated human cardiomyopathy exhibiting similar histopathologic abnormalities and premature death.", "A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.", "Here, a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), was identified in two families with hereditary heart failure. The heterozygous individuals exhibited hypertrophy without diminished contractile performance. Strikingly, both individuals homozygous for L39stop developed dilated cardiomyopathy and heart failure, requiring cardiac transplantation at ages 16 and 27. ", "Here we report that an inherited human dilated cardiomyopathy with refractory congestive heart failure is caused by a dominant Arg --> Cys missense mutation at residue 9 (R9C) in phospholamban (PLN), a transmembrane phosphoprotein that inhibits the cardiac sarcoplasmic reticular Ca2+-adenosine triphosphatase (SERCA2a) pump. Transgenic PLN(R9C) mice recapitulated human heart failure with premature death. Cellular and biochemical studies revealed that, unlike wild-type PLN, PLN(R9C) did not directly inhibit SERCA2a. Rather, PLN(R9C) trapped protein kinase A (PKA), which blocked PKA-mediated phosphorylation of wild-type PLN and in turn delayed decay of calcium transients in myocytes. ", "Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy.", "The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "http://www.ncbi.nlm.nih.gov/pubmed/22707725", "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "http://www.ncbi.nlm.nih.gov/pubmed/23568436", "http://www.ncbi.nlm.nih.gov/pubmed/23871674", "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "http://www.ncbi.nlm.nih.gov/pubmed/21332051", "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "http://www.ncbi.nlm.nih.gov/pubmed/16829191" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:0050700" ]

[ "There are several antioxidant supplements belonging to different families, i.e. Vitamins, Polyphenols, alpha-lipoic acid, ubiquinones, n-3- polyunsaturated acids (PUFAs), minerals and others. Nonetheless the widespread use of these supplements, it is still debated their true usefulness, and it is not unanimously advised their use in athletes." ]

[ "Resveratrol", "Quercetin", "Vitamin C", "Biostimine", "Astaxanthin", "Melatonin", "coenzyme Q(10)", "Creatine", "Isoquercetin", "Epigallocatechin gallate", "n-3 fatty acids", "L. rhamnosus IMC 501", "L. paracasei IMC 502", "docosahexanoic acid (DHA)", "eicosapentanoic acid (EPA)", "Rhodiola Rosea", "Vitamin E", "Zinc", "whey and/or soy proteins" ]

[ "Although these supplementations are increasingly used by master athletes, very few data are available on their effects on oxidative stress, muscle recovery, and physical performance. The potential benefits of supplement use in athletes are thus questionable. Some studies indicate no benefits, while others highlight potential negative side effects of vitamin supplementation. ", "These data indicate that RQ significantly reduces exercise-induced lipid peroxidation without associated changes in inflammation or plasma antioxidant status.", "Cr supplementation inhibited the increase of inflammation markers TNF-α and CRP, but not oxidative stress markers, due to acute exercise.", "Quercetin and vitamin C supplementation may not be beneficial in lipid profile improvement, although it may reduce induce muscle damage and body fat percent.", "Vitamins C and E supplementation had no significant effect on any of the studied parameters.", "Effects of the two treatments relative to placebo on mean performance in the incremental test and time trial were unclear, but runners faster by 1 SD of peak speed demonstrated a possible improvement on peak running speed with BC juice (1.9%; ±2.5%). ", "Training status correlates more strongly with antioxidant status than diet does", "Consequently, we can conclude that Biostimine supplementation reduces the postexercise level of TBARS by increasing the antioxidant activity of plasma but has no effect on inflammatory markers.", "Supplementation with Asx could prevent exercise induced free radical production and depletion of non-enzymatic antioxidant defense in young soccer players.", "In conclusion these results indicated that treatment with melatonin in acute sports exercise reversed oxidative stress, improved defenses and lipid metabolism, which would result in an improvement in fitness.", "CoQ(10) supplementation before strenuous exercise decreases the oxidative stress and modulates the inflammatory signaling, reducing the subsequent muscle damage.", "Heretofore, Cr's positive therapeutic benefits in various oxidative stress-associated diseases have been reported in the literature and, recently, Cr has also been shown to exert direct antioxidant effects.", "These results indicate that Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE.", "Nevertheless, based upon the growing evidence that many athletic populations are vitamin D deficient or insufficient, it is recommended that athletes monitor their serum vitamin D concentration and consult with their health care professional and/or nutritionist to determine if they would derive health benefits from vitamin D supplementation.", "This study examined the effects of 1,000 mg quercetin + 1,000 mg vitamin C (QC); 1,000 mg quercetin, 1,000 mg vitamin C, 400 mg isoquercetin, 30 mg epigallocatechin gallate, and 400 mg n-3 fatty acids (QFO)", "The two strains, L. rhamnosus IMC 501(®) and L. paracasei IMC 502(®), exert strong antioxidant activity. Athletes and all those exposed to oxidative stress may benefit from the ability of these probiotics to increase antioxidant levels and neutralize the effects of reactive oxygen species.", "These results indicate that supplementation with n-3 LCPUFAs significantly increased oxidative stress at rest and after a judo-training session.", "Rhodiola Rosea, is an adaptogen plant which has been reported to promote fatty acids utilisation, to ameliorate antioxidant function, and to improve body resistance to physical strenuous efforts. ", "Supplementation with antioxidant vitamin E to athletes at 267 mg (400 IUs) or greater has been reported to reduce levels of LP associated with exercise.", "Results obtained at the end of the study indicate that zinc supplementation prevents production of free radicals by activating the antioxidant system.", "The significant increase in the UI of erythrocyte membranes indicates the potential for harm, because a high intake of PUFA might increase susceptibility to lipid peroxidation not counterbalanced by a higher increase in TAA. Adherence to the Mediterranean diet seems to be the better choice.", "A number of clinical trials have successfully been performed using whey and/or soy proteins in the treatment of many diseases. They both have antioxidant properties, which appears to be a factor in aerobic physical performance as well. ", "The antioxidant effect of the two proteins is based on different mechanisms of action." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24323888", "http://www.ncbi.nlm.nih.gov/pubmed/21830999", "http://www.ncbi.nlm.nih.gov/pubmed/19089749", "http://www.ncbi.nlm.nih.gov/pubmed/23980734", "http://www.ncbi.nlm.nih.gov/pubmed/22828460", "http://www.ncbi.nlm.nih.gov/pubmed/23349254", "http://www.ncbi.nlm.nih.gov/pubmed/21116022", "http://www.ncbi.nlm.nih.gov/pubmed/23717772", "http://www.ncbi.nlm.nih.gov/pubmed/22212240", "http://www.ncbi.nlm.nih.gov/pubmed/21813916", "http://www.ncbi.nlm.nih.gov/pubmed/23600891", "http://www.ncbi.nlm.nih.gov/pubmed/21990004", "http://www.ncbi.nlm.nih.gov/pubmed/20308973", "http://www.ncbi.nlm.nih.gov/pubmed/21400082", "http://www.ncbi.nlm.nih.gov/pubmed/19597720", "http://www.ncbi.nlm.nih.gov/pubmed/23436649", "http://www.ncbi.nlm.nih.gov/pubmed/22080314", "http://www.ncbi.nlm.nih.gov/pubmed/23717765", "http://www.ncbi.nlm.nih.gov/pubmed/23800565", "http://www.ncbi.nlm.nih.gov/pubmed/18562771", "http://www.ncbi.nlm.nih.gov/pubmed/19838998", "http://www.ncbi.nlm.nih.gov/pubmed/16575496" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000975", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019587", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ]

[ "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration.", "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D" ]

[ "yes" ]

[ "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D", "Dominant mutations in GARS cause rare forms of Charcot-Marie-Tooth disease and distal spinal muscular atrophy", "Using exome sequencing she was found to harbor compound heterozygous mutations within the glycyl-tRNA synthetase (GARS) gene", "mutations of human GlyRS (hGlyRS) were also found to be associated with Charcot-Marie-Tooth disease", "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration", "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement", "Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V)", "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase.", "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.", "[A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement].", "Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V).", "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system.", "Here, we report the identification of four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with CMT2D and dSMA-V.", "Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D.", "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS).", "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)", "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS", "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase", "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system", "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement.", "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). ", "Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D. ", "An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.", "We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. ", "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model.", "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. ", "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration. ", " Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood.", "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease,", " Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D.", "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS).", "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase.", "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.", "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system.", "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement.", "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model.", "Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "http://www.ncbi.nlm.nih.gov/pubmed/12690580", "http://www.ncbi.nlm.nih.gov/pubmed/24669931", "http://www.ncbi.nlm.nih.gov/pubmed/24368416", "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "http://www.ncbi.nlm.nih.gov/pubmed/23279345", "http://www.ncbi.nlm.nih.gov/pubmed/23990368", "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "http://www.ncbi.nlm.nih.gov/pubmed/24898252", "http://www.ncbi.nlm.nih.gov/pubmed/19470612" ]

[]

[]

[ "FISH is a popular molecular cytogenetic method. The output of a single FISH analysis is a set of several tens or hundreds microscopic images — a single evaluated sample is of roughly 20mm diameter. The goal of an automated evaluation is to replace the subjective evaluation of images by the laboratory technician to achieve higher uniformity of results. Following explanation of the principle of the method and the typical contents of images, the processing flow of image segmentation is outlined and the results are presented on several example images. Based on results there are software for automated analysis of FISH images." ]

[ "yes" ]

[ "he study demonstrated the feasibility of automated FISH signal analysis that applying a CAD scheme to the automated generated 2-D projection images.", "A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, …,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M-FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods.", "hybridization (FISH) tests provide promising molecular imaging biomarkers to more accurately and reliably detect and diagnose cancers and genetic disorders. Since current manual FISH signal analysis is low-efficient and inconsistent, which limits its clinical utility, developing automated FISH image scanning systems and computer-aided detection (CAD) schemes has been attracting research interests. To acquire high-resolution FISH images in a multi-spectral scanning mode, a huge amount of image data with the stack of the multiple three-dimensional (3-D) image slices is generated from a single specimen. Automated preprocessing these scanned images to eliminate the non-useful and redundant data is important to make the automated FISH tests acceptable in clinical applications. In this study, a dual-detector fluorescence image scanning system was applied to scan four specimen slides with FISH-probed chromosome X. A CAD scheme was developed to detect analyzable interphase cells and map the multiple imaging slices recorded FISH-probed signals into the 2-D projection images. CAD scheme was then applied to each projection image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm, identify FISH-probed signals using a top-hat transform, and compute the ratios between the normal and abnormal cells. To assess CAD performance, the FISH-probed signals were also independently visually detected by an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots in four testing samples.", " In this paper we developed a sparse representation-based classification (SRC) algorithm based on L1-norm minimization for classifying chromosomes from multicolor fluorescence in situ hybridization (M-FISH) images. The algorithm has been tested on a comprehensive M-FISH database that we established, demonstrating improved performance in classification. When compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering algorithms that we proposed earlier the current method gave the lowest classification error. In order to evaluate the performance of different SRC for M-FISH imaging analysis, three different sparse representation methods, namely, Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression (LARS), were tested and compared. Results from our statistical analysis have shown that Homotopy based method is significantly better than the other two methods. ", "Fluorescence in situ hybridization (FISH) is used to study the organization and the positioning of specific DNA sequences within the cell nucleus. Analyzing the data from FISH images is a tedious process that invokes an element of subjectivity. Automated FISH image analysis offers savings in time as well as gaining the benefit of objective data analysis. While several FISH image analysis software tools have been developed, they often use a threshold-based segmentation algorithm for nucleus segmentation. As fluorescence signal intensities can vary significantly from experiment to experiment, from cell to cell, and within a cell, threshold-based segmentation is inflexible and often insufficient for automatic image analysis, leading to additional manual segmentation and potential subjective bias. To overcome these problems, we developed a graphical software tool called FISH Finder to automatically analyze FISH images that vary significantly. By posing the nucleus segmentation as a classification problem, compound Bayesian classifier is employed so that contextual information is utilized, resulting in reliable classification and boundary extraction. This makes it possible to analyze FISH images efficiently and objectively without adjustment of input parameters. Additionally, FISH Finder was designed to analyze the distances between differentially stained FISH probes.", "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217.", "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells. ", "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21310746", "http://www.ncbi.nlm.nih.gov/pubmed/22665392", "http://www.ncbi.nlm.nih.gov/pubmed/21656271", "http://www.ncbi.nlm.nih.gov/pubmed/16749443", "http://www.ncbi.nlm.nih.gov/pubmed/17889539", "http://www.ncbi.nlm.nih.gov/pubmed/23903043", "http://www.ncbi.nlm.nih.gov/pubmed/15887538", "http://www.ncbi.nlm.nih.gov/pubmed/17674627", "http://www.ncbi.nlm.nih.gov/pubmed/22935778", "http://www.ncbi.nlm.nih.gov/pubmed/22163442", "http://www.ncbi.nlm.nih.gov/pubmed/20639591", "http://www.ncbi.nlm.nih.gov/pubmed/15351517", "http://www.ncbi.nlm.nih.gov/pubmed/11818019", "http://www.ncbi.nlm.nih.gov/pubmed/24240725", "http://www.ncbi.nlm.nih.gov/pubmed/20966547" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007091", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984" ]

[ "Histone methyltransferases (HMTs) are responsible for the site-specific addition of covalent modifications on the histone tails, which serve as markers for the recruitment of chromatin organization complexes. There are two major types of HMTs: histone-lysine N-Methyltransferases and histone-arginine N-methyltransferases. The former methylate specific lysine (K) residues such as 4, 9, 27, 36, and 79 on histone H3 and residue 20 on histone H4. The latter methylate arginine (R) residues such as 2, 8, 17, and 26 on histone H3 and residue 3 on histone H4. Depending on what residue is modified and the degree of methylation (mono-, di- and tri-methylation), lysine methylation of histones is linked to either transcriptionally active or silent chromatin." ]

[]

[ "Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage.", "This approach identified Txr1p as a histone methyltransferase in Tetrahymena thermophila and characterized the relationships of the Txr1p and Ezl2p methyltransferases to histone H3 modification.", "Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1-MLL4) whose specific functions are largely unknown. ", "Epigenetic regulation of gene expression by covalent modification of histones is important for germ line cell development. In mammals, histone H3 lysine 9 (H3K9)-specific histone methyltransferases (HMTases), such as G9a, SETDB1, and SUV39H, play critical roles, but the contribution of H3K9-specific HMTases in Drosophila remains to be clarified, especially in male sperm.", "By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. ", " Here, we found the epigenetic modification of the BZLF1 promoter in latent Raji cells by histone H3 lysine 27 trimethylation (H3K27me3), H3K9me2/me3, and H4K20me3. ", "Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. ", "Methylation of histone H4 lysine 20 (H4K20me) plays critical roles in diverse cellular processes such as gene expression, cell cycle progression and DNA damage repair, with each of the three degrees of methylation (mono-, di- and tri-methylation) making a unique contribution. ", "Histone H3-lysine (K) 4, H3-K9 and H3-K27 modifications in all these four genes were examined by chromatin immunoprecipitation (ChIP) assay in HCC cell lines. ", "The histone H4 N-terminal tail has long been regarded as a major regulator in chromatin structure and function.", "Gene transcription is critically influenced by chromatin structure and the modification status of histone tails. Methylation of lysine residues in histone tails is dynamically regulated by the opposing activities of histone methyltransferases and histone demethylases.", "The SAS3-dependent NuA3 histone acetyltransferase complex was originally identified on the basis of its ability to acetylate histone H3 in vitro.", "SU(VAR)3-9 like histone methyltransferases control heterochromatic domains in eukaryotes.", "Methylation of position-specific lysine residues in histone N termini is a central modification for regulating epigenetic transitions in chromatin. Each methylatable lysine residue can exist in a mono-, di-, or trimethylated state, thereby extending the indexing potential of this particular modification. ", "One of these modifications, histone lysine methylation, has been shown to be highly stable and to represent an epigenetic alteration.", "Primarily because of the recent discovery of the SET domain-depending H3-specific histone methyltransferases SUV39H1 and Suv39h1, which selectively methylate lysine 9 of the H3 N terminus, this posttranslational modification has regained scientific interest.", "Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation.", "Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.", "Among the different groups of enzymes known to catalyze the covalent modification, the most recent additions are the histone methyltransferases (HMTases), whose functions are now being characterized." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19571682", "http://www.ncbi.nlm.nih.gov/pubmed/20026581", "http://www.ncbi.nlm.nih.gov/pubmed/17468742", "http://www.ncbi.nlm.nih.gov/pubmed/12893173", "http://www.ncbi.nlm.nih.gov/pubmed/22393255", "http://www.ncbi.nlm.nih.gov/pubmed/11316813", "http://www.ncbi.nlm.nih.gov/pubmed/18231586", "http://www.ncbi.nlm.nih.gov/pubmed/17548343", "http://www.ncbi.nlm.nih.gov/pubmed/17584191", "http://www.ncbi.nlm.nih.gov/pubmed/18058811", "http://www.ncbi.nlm.nih.gov/pubmed/22483804", "http://www.ncbi.nlm.nih.gov/pubmed/16581777", "http://www.ncbi.nlm.nih.gov/pubmed/20305384", "http://www.ncbi.nlm.nih.gov/pubmed/14690609", "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "http://www.ncbi.nlm.nih.gov/pubmed/18846226", "http://www.ncbi.nlm.nih.gov/pubmed/22476432", "http://www.ncbi.nlm.nih.gov/pubmed/11850410", "http://www.ncbi.nlm.nih.gov/pubmed/15775980", "http://www.ncbi.nlm.nih.gov/pubmed/16409643", "http://www.ncbi.nlm.nih.gov/pubmed/12154089", "http://www.ncbi.nlm.nih.gov/pubmed/23150054", "http://www.ncbi.nlm.nih.gov/pubmed/17846168", "http://www.ncbi.nlm.nih.gov/pubmed/18498648", "http://www.ncbi.nlm.nih.gov/pubmed/23195220" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016570", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008469" ]

[ "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis ", "Yes. Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer. Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST)", "People with Dyskeratosis Congenita are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis." ]

[ "yes" ]

[ "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis", "Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer.", "Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST)", "Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients", "The findings demonstrate that both FA and DC are major cancer susceptibility syndromes", "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis", "Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity.", "Dyskeratosis congenita (DC) is characterized by the clinical triad of reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with bone marrow failure (BMF) and an high risk to develop cancer and pulmonary complications.", "CONCLUSION: Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients.", "Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer.", "Dyskeratosis Congenita (DC) also known as Zinsser-Engman-Cole syndrome is a rare multi-system bone marrow failure syndrome characterised by mucocutaneous abnormalities and an increased predisposition to cancer\".", "Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities.", "Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients.", "Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients.", "Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment.", "Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity", "Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients", "Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities", "While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients", "As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita", "Severe pancytopenia frequently causes early mortality of DC patients, who have an increased risk of developing oropharyngeal squamous cell carcinoma", "Here different aspects of telomere biology, concerning adult stem cells senescence, tumor suppression and cancer are considered in the context of DC, resulting in two translational models: late onset of DC symptoms in telomere-related mutations carriers is a potential indicator of increased cancer risk and differences in tumor suppression capacities among the genetic subgroups are (at least partial) causes of different clinical manifestations of the disease", "Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer", "Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19327580", "http://www.ncbi.nlm.nih.gov/pubmed/20925138", "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "http://www.ncbi.nlm.nih.gov/pubmed/23619122", "http://www.ncbi.nlm.nih.gov/pubmed/18938267", "http://www.ncbi.nlm.nih.gov/pubmed/23352883", "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "http://www.ncbi.nlm.nih.gov/pubmed/22362038", "http://www.ncbi.nlm.nih.gov/pubmed/19558498", "http://www.ncbi.nlm.nih.gov/pubmed/22932338", "http://www.ncbi.nlm.nih.gov/pubmed/22058220", "http://www.ncbi.nlm.nih.gov/pubmed/17825470", "http://www.ncbi.nlm.nih.gov/pubmed/23541441", "http://www.ncbi.nlm.nih.gov/pubmed/24034063", "http://www.ncbi.nlm.nih.gov/pubmed/18054794" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.disease-ontology.org/api/metadata/DOID:2729", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369" ]

[ "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches" ]

[ "yes" ]

[ "The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis.", "Taken together, we found a novel reciprocal loop between miR-21 and TGFβRIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling.", "It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis.", "In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. ", "The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients.", "Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.", "Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.", "In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group.", "While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21.", "The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation.", "During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described.", "On the other hand, miR-21, miR-199a, miR-210, and miR-494 have been proven critical for the myocytes' adaptation and survival during hypoxia/ischemia. ", "Studies have shown that several miRs, including miR-1, miR-133, miR-21, miR-126, miR-320, miR-92a, and miR-199a, are regulated after preconditioning and play an active role in protecting the heart against ischemia/reperfusion injury.", "Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction.", "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches.", "miR-21 might be a novel therapeutic target in cardiovascular diseases.", "This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease.", "Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo.", "Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias.", "Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.", "The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.", "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts", "Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients", "MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis", "MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4", "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system.", "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.", "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system", "miR-21 might be a novel therapeutic target in cardiovascular diseases", "MicroRNA-21 as therapeutic target in cancer and cardiovascular disease.", "These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts.", "Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22960625", "http://www.ncbi.nlm.nih.gov/pubmed/23691029", "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/21712654", "http://www.ncbi.nlm.nih.gov/pubmed/19336275", "http://www.ncbi.nlm.nih.gov/pubmed/20219857", "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "http://www.ncbi.nlm.nih.gov/pubmed/21464712", "http://www.ncbi.nlm.nih.gov/pubmed/20015039", "http://www.ncbi.nlm.nih.gov/pubmed/22859901", "http://www.ncbi.nlm.nih.gov/pubmed/20649511", "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "http://www.ncbi.nlm.nih.gov/pubmed/19706597", "http://www.ncbi.nlm.nih.gov/pubmed/20980922" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.disease-ontology.org/api/metadata/DOID:1287" ]

[ "E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain.BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways.", "Discovering the precise function of the breast and ovarian specific tumor suppressor, BRCA1, has proven to be quite complicated. The protein encoded by BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric complex that acts as a ubiquitin E3 ligase. E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain." ]

[ "E3 ubiquitin ligase activity" ]

[ "E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain.", "BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways.", "E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks.", "The protein encoded by BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric complex that acts as a ubiquitin E3 ligase. Because the enzymatic activity of the BRCA1/BARD1 heterodimer is conserved over a broad phylogenetic range, it is thought to be critical for the central functions of BRCA1.", "A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase.", "In this study, we identified an ubiquitin-dependent mechanism by which BRCA1 inhibits transcription. BRCA1 ubiquitinates the transcriptional preinitiation complex, preventing stable association of TFIIE and TFIIH, and thus blocks the initiation of mRNA synthesis. ", "In the structure the arrangement of the Ring-domains is similar to another H2A E3 ligase, the BRCA1/BARD1 complex, but complex formation depends on an N-terminal arm of Ring1b that embraces the Bmi1 Ring-domain.", "Discovering the precise function of the breast and ovarian specific tumor suppressor, BRCA1, has proven to be quite complicated. It has been determined that BRCA1, together with BARD1, comprise an E3 ubiquitin ligase. Since it is now known that BRCA1 is an enzyme, the challenge for BRCA1 research is to learn how this enzymatic activity functions in normal breast and ovarian cells in order to suppress cancerous transformation.", "The BRCA1 tumor suppressor gene is expressed in all mammalian cells. Within these cells, the BRCA1 protein product interacts with several seemingly distinct nuclear complexes. Proteins within these complexes are potential targets for the E3-ubiquitin ligase activity associated with BRCA1:BARD1 complexes. ", "During both DNA replication and DNA repair, BRCA1 appears to serve both adaptor and enzymatic functions. Roles include transient physical recruitment of NBS1, gammaH2AX, FANCD2 and other proteins in specific repair associated complexes, and enzymatic activity as an E3-ubiquitin ligase against a subset of these proteins. ", "The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20681793", "http://www.ncbi.nlm.nih.gov/pubmed/24278741", "http://www.ncbi.nlm.nih.gov/pubmed/15254397", "http://www.ncbi.nlm.nih.gov/pubmed/16479151", "http://www.ncbi.nlm.nih.gov/pubmed/16710298", "http://www.ncbi.nlm.nih.gov/pubmed/17420471", "http://www.ncbi.nlm.nih.gov/pubmed/22034435", "http://www.ncbi.nlm.nih.gov/pubmed/19088202" ]

[]

[ "http://www.uniprot.org/uniprot/BRCA1_GORGO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070531" ]

[ "Expression of LC3-II and BECN1 as well as SQSTM1 are used as markers of autophagy activity." ]

[ "LC3-II", "microtubule-associated protein 1 light chain 3", "BECN1", "beclin 1", "SQSTM1", "p62", "Sequestosome 1" ]

[ ". Light chain 3/Atg8 as an autophagy marker ", "increased conversion of microtubule-associated protein, 1A/1B-light chain 3, from its cytosolic form (LC3B-I) to its lipidated form (LC3B-II), increased Beclin-1 levels, and increased acridine orange staining as determined by flow cytometry analysis, providing further evidence of γ-tocotrienol-induced autophagy in these mammary cancer cell lines", "Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3 (LC3)-II protein expression as a marker for autophagy", "autophagy marker LC3-II", "autophagy marker LC3B ", "the autophagy marker LC3", "autophagy marker molecules, p62 and LC3-II ", " LC3-I into LC3-II and has been confirmed in multiple mammalian cell lines with multiple autophagy markers ", " light chain 3 (LC3), which is an autophagy marker.", "LC3 (tfLC3) autophagy marker", "the autophagy marker LC3,", "autophagy marker beclin 1 and microtubule-associated protein light chain 3 (LC3) were analyzed in control, ", " LC3-II levels (an autophagy marker);", "autophagy marker, microtubule-associated protein light chain3 (LC3)", "the autophagy marker LC3B-II", "utophagy marker protein microtubule-associated protein 1 light chain 3 (LC3)", "autophagy marker LC3", "We used the expression of LC3-II and BECN1 as well as SQSTM1 as markers of autophagy activity. ", "autophagy marker LC3" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22807527", "http://www.ncbi.nlm.nih.gov/pubmed/23940944", "http://www.ncbi.nlm.nih.gov/pubmed/23193914", "http://www.ncbi.nlm.nih.gov/pubmed/23626658", "http://www.ncbi.nlm.nih.gov/pubmed/24141623", "http://www.ncbi.nlm.nih.gov/pubmed/24231340", "http://www.ncbi.nlm.nih.gov/pubmed/24126619", "http://www.ncbi.nlm.nih.gov/pubmed/24291536", "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "http://www.ncbi.nlm.nih.gov/pubmed/23608825", "http://www.ncbi.nlm.nih.gov/pubmed/23437259", "http://www.ncbi.nlm.nih.gov/pubmed/23737395", "http://www.ncbi.nlm.nih.gov/pubmed/23727153", "http://www.ncbi.nlm.nih.gov/pubmed/23182945", "http://www.ncbi.nlm.nih.gov/pubmed/23598404", "http://www.ncbi.nlm.nih.gov/pubmed/23117929", "http://www.ncbi.nlm.nih.gov/pubmed/22652752", "http://www.ncbi.nlm.nih.gov/pubmed/23822101" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000943", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343" ]

[ "Yes. ChIPnorm is a two-stage statistical method to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types." ]

[ "yes" ]

[ "ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites.", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. ", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. ", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods.", "This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22870189" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518" ]

[ "Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations. Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with Rheumatoid Arthritis disease activity." ]

[ "yes" ]

[ "The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1 × 10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients)", "Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity", " Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21094032", "http://www.ncbi.nlm.nih.gov/pubmed/21255096", "http://www.ncbi.nlm.nih.gov/pubmed/23555300" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001168", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.disease-ontology.org/api/metadata/DOID:7148" ]

[ "N-glycolylneuraminic acid (Neu5Gc) is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. N-Glycolylneuraminic acid (Neu5Gc) can be incorporated in human cells and can trigger immune response, a response that is diverse and polyclonal. As dietary Neu5Gc is primarily found in red meat and milk products, it is suggested that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans." ]

[ "Neu5Gc is an immune message to self" ]

[ "Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self", "N-glycolylneuraminic acid (Neu5Gc) is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. ", "N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid synthesized by animals, but not by humans or birds. However, it can be incorporated in human cells and can trigger immune response.", "Human heterophile antibodies that agglutinate animal erythrocytes are known to detect the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc). ", " the human anti-Neu5Gc antibody response is diverse and polyclonal.", "As dietary Neu5Gc is primarily found in red meat and milk products, we suggest that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans.", "These data suggest that anti-Neu5Gc Abs represent a barrier for long-term acceptance of porcine xenografts. Because anti-Neu5Gc Abs can promote chronic inflammation, the long-term safety of living and acellular pig tissue implants in recipients warrants further evaluation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25003133", "http://www.ncbi.nlm.nih.gov/pubmed/25124893", "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "http://www.ncbi.nlm.nih.gov/pubmed/23945141", "http://www.ncbi.nlm.nih.gov/pubmed/23520510", "http://www.ncbi.nlm.nih.gov/pubmed/11786991" ]

[]

[ "http://www.biosemantics.org/jochem#4256873", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019158" ]

[ "Currently, there is no specific antidote for rivaroxaban" ]

[ "no" ]

[ "Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs.", "he new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. ", "Given the absence of a specific antidote, the action to be taken in these situations must be defined. ", "The fact that there is no specific antidote to reverse the anticoagulant action of the new anticoagulants can impair management of hemorrhagic complications; ", "Like any new therapy, the potential benefits must be weighed against the potential challenges and one of the most concerning aspects of the new target-specific oral anticoagulants is the lack of a proven method to reverse their effect. Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. ", "Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes.", "NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication.", "But they have disadvantages also, they depend on renal clearance, they can interact with other medicaments and they lack a specific antidote. ", "While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in \"real-life\" clinical practice) still need to be elucidated.", "In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect.", "The short half-life of these new agents compensates for the lack of any specific antidote in many instances. ", "Currently, none of these new agents has a specific antidote, and little advise can be given on how to manage a major bleeding event.", "Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). ", "Increased use of dabigatran, rivaroxaban, and apixaban as oral anticoagulants for the treatment of atrial fibrillation and acute deep venous thrombosis has increased despite the lack of known antidotes to these medications.", "There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. ", "Further concerns about the use of NOAC in the elderly are the high prevalence of renal insufficiency in AF patients >75 years of age, the largely unknown risk of drug-drug and drug-food interactions, the lack of easily available laboratory monitoring tests of anticoagulant activity and the lack of an antidote.", "Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials.", "In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12871541", "http://www.ncbi.nlm.nih.gov/pubmed/23117666", "http://www.ncbi.nlm.nih.gov/pubmed/23312927", "http://www.ncbi.nlm.nih.gov/pubmed/19351313", "http://www.ncbi.nlm.nih.gov/pubmed/23657589", "http://www.ncbi.nlm.nih.gov/pubmed/24103671", "http://www.ncbi.nlm.nih.gov/pubmed/23810130", "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "http://www.ncbi.nlm.nih.gov/pubmed/20858186", "http://www.ncbi.nlm.nih.gov/pubmed/23628464", "http://www.ncbi.nlm.nih.gov/pubmed/23953907", "http://www.ncbi.nlm.nih.gov/pubmed/23866358", "http://www.ncbi.nlm.nih.gov/pubmed/23634925", "http://www.ncbi.nlm.nih.gov/pubmed/23460104", "http://www.ncbi.nlm.nih.gov/pubmed/23821689", "http://www.ncbi.nlm.nih.gov/pubmed/22353706", "http://www.ncbi.nlm.nih.gov/pubmed/23790307", "http://www.ncbi.nlm.nih.gov/pubmed/24170233", "http://www.ncbi.nlm.nih.gov/pubmed/22308807" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931", "http://www.biosemantics.org/jochem#4243836" ]

[ "Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37°C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. Cultures grown with elevated CO(2) /bicarbonate exhibited increased AtxA dimer/monomer ratios and increased AtxA activity, relative to cultures grown without added CO(2) /bicarbonate, suggesting that this host-associated signal enhances AtxA function by shifting the dimer/monomer equilibrium towards the dimeric state. CO2-enhanced toxin gene transcription is not observed in atx4-null mutants. Overall data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2. However, the steady-state level of atxA mRNA in cells grown in elevated CO2/bicarbonate at 37 degrees C is five- to sixfold higher than that observed in cells grown in the same conditions at 28 degrees C. A corresponding difference in AtxA protein was also seen at the different growth temperatures. All mutants multimerized, but one mutation, C402S, prevented cross-linking." ]

[ "CO2", "bicarbonate" ]

[ "Here we report that bioinformatic analyses suggested the presence in AtxA of two PTS (phosphenolpyruvate : sugar phosphotransferase system) regulation domains (PRD) generally regulated by phosphorylation/dephosphorylation at conserved histidine residues.", "Our results link virulence factor production in B. anthracis to carbohydrate metabolism and, for the first time, provide a mechanistic explanation for AtxA transcriptional activity.", "Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37°C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer.", "The 475 amino acid sequence of AtxA reveals DNA binding motifs and regions similar to proteins associated with the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS). ", "cultures grown with elevated CO(2) /bicarbonate exhibited increased AtxA dimer/monomer ratios and increased AtxA activity, relative to cultures grown without added CO(2) /bicarbonate, suggesting that this host-associated signal enhances AtxA function by shifting the dimer/monomer equilibrium towards the dimeric state.", "Transcription of the major Bacillus anthracis virulence genes is triggered by CO2, a signal mimicking the host environment. ", "Furthermore, in vitro in presence of CO2 and in vivo, AtxA is part of the sap and eag regulatory network. ", "Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: temperature, not CO2/bicarbonate, affects AtxA synthesis.", " In atxA+ strains, expression of the toxin genes (pag, lef, and cya) is enhanced by two physiologically significant signals: elevated CO2/bicarbonate and temperature. ", "Our data indicate that atxA expression is not influenced by CO2/bicarbonate levels. However, the steady-state level of atxA mRNA in cells grown in elevated CO2/bicarbonate at 37 degrees C is five- to sixfold higher than that observed in cells grown in the same conditions at 28 degrees C. ", "The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2", "CO2-enhanced toxin gene transcription is not observed in atx4-null mutants.", "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. ", "Transposon-insertion libraries were screened for mutants expressing CO2-enhanced atxA-dependent beta-galactosidase activity. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. ", "data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin gene expression in Bacillus anthracis.", "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism", "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate. ", "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism.", "Expression of the toxin genes by B. anthracis is enhanced during growth under elevated levels of CO2.", "This CO2 effect is observed only in the presence of another pXO1 gene, atxA, which encodes a transactivator of anthrax toxin synthesis.", "Here we show that transcription of atxA does not appear to differ in cells grown in 5% CO2 compared with cells grown in air.", "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate. Deletion analysis of the upstream region of the cap promoter revealed that activation by both atxA and acpA required a DNA segment of 70 bp extending upstream of the P1 site.", "We identified two major apparent transcriptional start sites, designated P1 and P2, located at positions 731 bp and 625 bp, respectively, upstream of the translation-initiation codon of capB. Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: temperature, not CO2/bicarbonate, affects AtxA synthesis.", "The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin gene expression in Bacillus anthracis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "http://www.ncbi.nlm.nih.gov/pubmed/15149039", "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "http://www.ncbi.nlm.nih.gov/pubmed/17302798" ]

[]

[ "http://www.uniprot.org/uniprot/ATXA_BACAN" ]

[ "6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. The carboxy terminus containing the Arg-Gly-Gly (RGG) repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain.", "Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. 6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription. 6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation. 6S RNA acts as a template for the transcription of defined RNA molecules in the absence of DNA. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase.", "6S RNA function enhances long-term cell survival. " ]

[]

[ "Qbeta replicase lacking subunit alpha (R-alpha) is capable of replicating templates other than (+) strand, such as (--), \"6S\" RNA, poly(C) etc., in the absence of the host factor.", "Escherichia coli 6S RNA gene is part of a dual-function transcription unit.", "The DNA sequence results confirm the accuracy of the previously established RNA sequence and, with genomic hybridization data, reveal that there is only one copy of the 6S DNA in the chromosome. Consistent with its relaxed mode of expression, the promoter region of the 6S RNA gene was found to lack the hypothetical GC-rich discriminator domain common to other stable RNA genes under stringent control. The sequence results also revealed the occurrence of a 540-base-pair open reading frame immediately downstream from the 6S RNA coding region.", "6S RNA function enhances long-term cell survival.", "6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription.", "6S RNA inhibition of sigma(70)-dependent transcription was not ubiquitous, in spite of the fact that the vast majority of sigma(70)-RNA polymerase is bound by 6S RNA during stationary phase.", "The sigma(70)-dependent promoters inhibited by 6S RNA contain an extended -10 promoter element, suggesting that this feature may define a class of 6S RNA-regulated genes.", " a secondary effect of 6S RNA in the activation of sigma(S)-dependent transcription at several promoters.", "6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation.", "Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. ", "Preferred binding of 6S RNA to Esigma(70) was confirmed, however weaker binding to Esigma(38) was also observed.", "Moreover, we show for the first time that 6S RNA acts as a template for the transcription of defined RNA molecules in the absence of DNA. In conclusion, this study reveals new aspects of 6S RNA function.", "6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase", "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA ∼ pRNA complexes to investigate the molecular details leading to the release reaction", "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA ∼ pRNA complexes to investigate the molecular details leading to the release reaction. ", "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA ∼ pRNA complexes to investigate the molecular details leading to the release reaction." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/58611", "http://www.ncbi.nlm.nih.gov/pubmed/17332013", "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "http://www.ncbi.nlm.nih.gov/pubmed/23667906", "http://www.ncbi.nlm.nih.gov/pubmed/22214309", "http://www.ncbi.nlm.nih.gov/pubmed/2579060" ]

[]

[]

[ "Yes, one clinical trial that directly compared smoking cessation rates with cytisine versus nicotine replacement therapy reported that cytisine was superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events." ]

[ "yes" ]

[ "The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men.", "CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22513936", "http://www.ncbi.nlm.nih.gov/pubmed/21154363", "http://www.ncbi.nlm.nih.gov/pubmed/17130378", "http://www.ncbi.nlm.nih.gov/pubmed/24574554", "http://www.ncbi.nlm.nih.gov/pubmed/25517706", "http://www.ncbi.nlm.nih.gov/pubmed/17825502", "http://www.ncbi.nlm.nih.gov/pubmed/24831822", "http://www.ncbi.nlm.nih.gov/pubmed/21328282", "http://www.ncbi.nlm.nih.gov/pubmed/22104038", "http://www.ncbi.nlm.nih.gov/pubmed/18076335", "http://www.ncbi.nlm.nih.gov/pubmed/17220536", "http://www.ncbi.nlm.nih.gov/pubmed/21385905", "http://www.ncbi.nlm.nih.gov/pubmed/18646137", "http://www.ncbi.nlm.nih.gov/pubmed/20040957", "http://www.ncbi.nlm.nih.gov/pubmed/23834141", "http://www.ncbi.nlm.nih.gov/pubmed/23404838", "http://www.ncbi.nlm.nih.gov/pubmed/17253581", "http://www.ncbi.nlm.nih.gov/pubmed/23978314", "http://www.ncbi.nlm.nih.gov/pubmed/23728690" ]

[]

[ "http://www.biosemantics.org/jochem#4273701", "http://www.biosemantics.org/jochem#4251343" ]

[ "CADASIL is caused mostly by missense mutations in the NOTCH3 gene, invariably involving a cysteine residue." ]

[ "Cysteine" ]

[ "missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear", "CADASIL is caused mostly by missense mutations in the NOTCH3 gene, invariably involving a cysteine residue.", "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations involving loss or gain of a cysteine residue in the NOTCH3 gene. A cluster of mutations around exons 3 and 4 was originally reported", "The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18313300", "http://www.ncbi.nlm.nih.gov/pubmed/24086431", "http://www.ncbi.nlm.nih.gov/pubmed/11706120", "http://www.ncbi.nlm.nih.gov/pubmed/23587639", "http://www.ncbi.nlm.nih.gov/pubmed/15304596", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/21038489", "http://www.ncbi.nlm.nih.gov/pubmed/21616505", "http://www.ncbi.nlm.nih.gov/pubmed/19043263", "http://www.ncbi.nlm.nih.gov/pubmed/16717210", "http://www.ncbi.nlm.nih.gov/pubmed/17726918", "http://www.ncbi.nlm.nih.gov/pubmed/23799017", "http://www.ncbi.nlm.nih.gov/pubmed/22367627", "http://www.ncbi.nlm.nih.gov/pubmed/20224942", "http://www.ncbi.nlm.nih.gov/pubmed/22082899", "http://www.ncbi.nlm.nih.gov/pubmed/18710532", "http://www.ncbi.nlm.nih.gov/pubmed/23597439", "http://www.ncbi.nlm.nih.gov/pubmed/19006080", "http://www.ncbi.nlm.nih.gov/pubmed/22623959" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "UMLS_CUI:C0751587" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "cadasil" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "MSH2010_2010_02_22:D046589" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "Notch homolog 3 (Drosophila) protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "NOTCH3 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400718" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400738" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "CADASIL protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17705411", "o": "CADASIL Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17683439", "o": "CADASIL Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12021175", "o": "CADASIL" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6957136", "o": "CADASIL" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/genes" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL", "o": "CADASIL" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1802", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024342", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000596", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.disease-ontology.org/api/metadata/DOID:13945" ]

[ "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined. Recent studies have shown that EZH2 mutations are often associated with RUNX1 mutations in MDS patients, although its pathological function remains to be addressed. These data show that mutations in EZH2 cause Weaver syndrome. The EZH2 gene is a homolog of the Drosophila Polycomb group (PcG) gene enhancer of zest, a crucial regulator of homeotic gene expression.", "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML). Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL). The EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukaemia." ]

[ "myelodysplastic syndrome (MDS)", "Acquired aplastic anemia (AA)", "Weaver syndrome", "non-Hodgkin lymphoma (NHL)", "myeloid leukaemia" ]

[ "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML)", "We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH result", " Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure.", "Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined", "Weaver syndrome and EZH2 mutations", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. ", "Mutations in EZH2 cause Weaver syndrome", "These data show that mutations in EZH2 cause Weaver syndrome", "The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies", "EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.", "Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL)", "The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN).", "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome.", "Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively.", "Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "We postulated that mutations in writers of these two chromatin marks could cause overgrowth conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or EZH2 abnormalities.", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). ", "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. ", "Recently, the advent of next generation sequencing (NGS) techniques has helped identify somatic gene mutations in 75-80% of MDS, that cluster mainly in four functional groups, i.e. cytokine signaling (RAS genes), DNA methylation, (TET2, IDH1/2, DNMT3a genes) histone modifications (ASXL1 and EZH2 genes), and spliceosome (SF3B1 and SRSF2 genes) along with mutations of RUNX1 and TP 53 genes.", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 mutations that cause Sotos syndrome are loss-of-function, primarily truncating mutations or missense mutations at key residues in functional domains.", "EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "The deletion involved multiple genes, including two tumor suppressor candidate genes (CTNNA1 and HSPA9) that are associated with MDS/AML.", "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21856302", "http://www.ncbi.nlm.nih.gov/pubmed/24507812", "http://www.ncbi.nlm.nih.gov/pubmed/24953053", "http://www.ncbi.nlm.nih.gov/pubmed/10780782", "http://www.ncbi.nlm.nih.gov/pubmed/24218139", "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "http://www.ncbi.nlm.nih.gov/pubmed/23099237", "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "http://www.ncbi.nlm.nih.gov/pubmed/22475286", "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "http://www.ncbi.nlm.nih.gov/pubmed/24760151" ]

[]

[ "http://www.uniprot.org/uniprot/EZH2_MACFA", "http://www.uniprot.org/uniprot/EZH2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ]

[ "ExTopoDB and TMPDB." ]

[ "ExTopoDB", "TMPDB" ]

[ "ExTopoDB: a database of experimentally derived topological models of transmembrane proteins", "ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins. It contains information collected from studies in the literature that report the use of biochemical methods for the determination of the topology of α-helical transmembrane proteins. Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of α-helical transmembrane proteins. Topological information is combined with transmembrane topology prediction resulting in more reliable topological models. AVAILABILITY: http://bioinformatics.biol.uoa.gr/ExTopoDB", "TMPDB: a database of experimentally-characterized transmembrane topologies", "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies. TMPDB release 6.2 contains a total of 302 TM protein sequences, in which 276 are alpha-helical sequences, 17 beta-stranded, and 9 alpha-helical sequences with short pore-forming helices buried in the membrane. The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods. TMPDB would be useful as a test and/or training dataset in improving the proposed TM topology prediction methods or developing novel methods with higher performance, and as a guide for both the bioinformaticians and biologists to better understand TM proteins. TMPDB and its subsets are freely available at the following web site: http://bioinfo.si.hirosaki-u.ac.jp/~TMPDB/", "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of ж┴-helical transmembrane proteins.", "TMPDB: a database of experimentally-characterized transmembrane topologies.", "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies.", "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods.", "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of α-helical transmembrane proteins.", "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of �-helical transmembrane proteins.", "UNLABELLED: ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins.", "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods.", "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of α-helical transmembrane proteins", "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods", "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies", "ExTopoDB: a database of experimentally derived topological models of transmembrane proteins.", "ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "http://www.ncbi.nlm.nih.gov/pubmed/20601677" ]

[]

[]

[ "Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. ", "The medical condition characterized by the congenital absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract is called aganlionic megacolon or Hirschsprung disease.", "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract.This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells.", "Hirschsprungs disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells." ]

[ "Aganlionic megacolon or Hirschsprung disease" ]

[ "Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS).", "This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells.", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract.", "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract.", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "Hirschsprung's disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerves forming the plexus of the lower intestine.", "Hirschsprung disease (HSCR) is an inherited disorder characterised by absence of intrinsic ganglion cells in the distal gastrointestinal tract.", "Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut.", "Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract.", "BACKGROUND: Hirschsprungs Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissners) and myenteric (Aurbachs) plexuses of distal bowel.", "Hirschsprung's disease is an inherited disorder characterized by the absence of ganglion cells in the distal bowel.", "Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of ganglion cells in various length of distal digestive tract", "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract", "Hirschsprung's disease (HSCR) is a congenital intestinal disease, characterized by the absence of ganglion cells in the distal portion of the intestinal tract", "Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells along with variable lengths of the gastrointestinal tract", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon", "Hirschsprung's disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerves forming the plexus of the lower intestine", "Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut", "Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract", "Hirschsprung disease (HSCR) is an inherited disorder characterised by absence of intrinsic ganglion cells in the distal gastrointestinal tract", "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23272425", "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "http://www.ncbi.nlm.nih.gov/pubmed/23836442", "http://www.ncbi.nlm.nih.gov/pubmed/9556633", "http://www.ncbi.nlm.nih.gov/pubmed/10980580", "http://www.ncbi.nlm.nih.gov/pubmed/22184102", "http://www.ncbi.nlm.nih.gov/pubmed/20860806", "http://www.ncbi.nlm.nih.gov/pubmed/8401580", "http://www.ncbi.nlm.nih.gov/pubmed/21656899", "http://www.ncbi.nlm.nih.gov/pubmed/22974608", "http://www.ncbi.nlm.nih.gov/pubmed/23043324", "http://www.ncbi.nlm.nih.gov/pubmed/8894691", "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "http://www.ncbi.nlm.nih.gov/pubmed/16080919" ]

[]

[]

[ "Fanconi anemia (FA) is an autosomal disorder that causes genome instability and manifests by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations.", "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations. ", "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations." ]

[ "Fanconi anemia" ]

[ "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations.", "Fanconi anemia (FA) is characterized at the cellular level by a high frequency of spontaneous chromosomal aberrations; crosslinking agents cause an abnormal increase in the frequency of chromosomal damage, and semiconservative DNA synthesis is severely inhibited.", "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia.", "Cells from patients wtih Fanconi's anemia are unusually sensitive to agents which are capable of crosslinking DNA.", "An elevated frequency of chromosome aberrations, which is further exaggerated by exposure of cells to DNA crosslinking agents, is a general feature of Fanconi's anemia.", "FA patients exhibit spontaneous chromosome breakage and FA cells are sensitive to DNA interstrand crosslink agents and expresses high frequency of chromosome breakage", "Fanconi anemia (FA) is characterized at the cellular level by a high frequency of spontaneous chromosomal aberrations; crosslinking agents cause an abnormal increase in the frequency of chromosomal damage, and semiconservative DNA synthesis is severely inhibited", "Cells from patients wtih Fanconi's anemia are unusually sensitive to agents which are capable of crosslinking DNA", "At the cellular level, FA is characterized by hypersensitivity to DNA cross-linking agents and by high frequencies of induced chromosomal aberrations, a property used for diagnosis", "An elevated frequency of chromosome aberrations, which is further exaggerated by exposure of cells to DNA crosslinking agents, is a general feature of Fanconi's anemia", "Similarly, Fanconi's anemia cells, which are chromosomally sensitive to crosslinking agents, and appear to be defective in the \"unhooking\" of linked polynucleotide strands [15, 16, 49, 51], are reported to be chromosomally sensitive to ethyl methanesulfonate as well [29], and to be sensitive to ionizing radiation [7, 19, ]0], again implying overlapping repair systems" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20132664", "http://www.ncbi.nlm.nih.gov/pubmed/8876687", "http://www.ncbi.nlm.nih.gov/pubmed/7011307", "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "http://www.ncbi.nlm.nih.gov/pubmed/21568838", "http://www.ncbi.nlm.nih.gov/pubmed/16115458", "http://www.ncbi.nlm.nih.gov/pubmed/8058745" ]

[]

[]

[ "Oprozomib is administered orally." ]

[ "Orally" ]

[ "Further, new orally administered second-generation PI oprozomib is being investigated. ", "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "This review provides an overview of the role of oral proteasome inhibitors including Marizomib, Oprozomib, Delanzomib, chemical proteasome inhibitors, and cinnabaramides, in the therapy of MM, focusing on developments over the past five years. ", "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "Further, new orally administered second-generation PI oprozomib is being investigated.", "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.", "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics.", "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "Further, new orally administered second-generation PI oprozomib is being investigated", "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat", "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.", "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed. ", "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. ", "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. ", "new orally administered second-generation PI oprozomib is being investigated.", "including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed.", "Finally, we found that DC incubation with the drug(s) enhanced IκB expression and that oprozomib inhibited NF-κB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "http://www.ncbi.nlm.nih.gov/pubmed/24239172" ]

[]

[]

[ "Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids." ]

[]

[ "Caveolae are flask-shaped plasma membrane invaginations formed by constitutive caveolin proteins and regulatory cavin proteins. ", "Caveolae are membrane subdomains that function as signaling platforms, endocytic carriers, sensors of membrane tension, and mechanical stress, as well as in lipid homeostasis", "Caveolae are cholesterol-rich microdomains that form mechanically deformable invaginations of the sarcolemma.", "Caveolae are specialized membrane lipid rafts coated with caveolin scaffolding proteins,", " Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced.", "Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids.", "The efficiency of youth is built upon cellular signaling scaffolds that provide tight and coordinated signaling. Lipid rafts are one such scaffold of which caveolae are a subset.", "Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types", "Caveolae are non-clathrin invaginations of the plasma membrane in most cell types", "Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane.", "Caveolae are an abundant feature of the plasma membrane of many mammalian cell types, " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24013648", "http://www.ncbi.nlm.nih.gov/pubmed/23899671", "http://www.ncbi.nlm.nih.gov/pubmed/23727353", "http://www.ncbi.nlm.nih.gov/pubmed/24023653", "http://www.ncbi.nlm.nih.gov/pubmed/23593340", "http://www.ncbi.nlm.nih.gov/pubmed/23340574", "http://www.ncbi.nlm.nih.gov/pubmed/23521716", "http://www.ncbi.nlm.nih.gov/pubmed/23787000", "http://www.ncbi.nlm.nih.gov/pubmed/7407830", "http://www.ncbi.nlm.nih.gov/pubmed/24308657", "http://www.ncbi.nlm.nih.gov/pubmed/23610576", "http://www.ncbi.nlm.nih.gov/pubmed/24013596" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1304410", "o": "4007-0024" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1304410", "o": "caveola intracellularis" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0598071", "o": "http://linkedlifedata.com/resource/umls/label/A1304410" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0598071", "o": "http://linkedlifedata.com/resource/umls/label/A1304410" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "host caveola" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2752448", "o": "http://linkedlifedata.com/resource/umls/id/C2247081" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14274436", "o": "host cell membrane" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2752448", "o": "http://linkedlifedata.com/resource/umls/label/A17471949" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17471949", "o": "host caveola" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17471949", "o": "Gene Ontology" }, { "p": "http://linkedlifedata.com/resource/geneontology/part_of", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0033644" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0033644", "o": "host cell membrane" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0072584", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005901", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070836" ]

[ "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements. Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Therefore, concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments is important in orchestrating events required for efficient gene expression." ]

[ "providing complex regulation", "facilitating matching genes and regulatory elements", "efficient trancription" ]

[ "concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments will be important in orchestrating events required for efficient gene expression.", "Chromatin domains and nuclear compartments: establishing sites of gene expression in eukaryotic nuclei.", "Using the adult bovine lens as a model system, nuclear changes accompanying denucleation are described with particular emphasis on the lamina, nucleolar and coiled body compartments in lens nuclei.", "Changes in the nucleolar and coiled body compartments precede lamina and chromatin reorganization during fibre cell denucleation in the bovine lens", "Prior to chromatin condensation, coilin redistributed to the nucleolar compartment and was absent from nuclei where chromatin had begun to condense.", "These constraints reflect the physical attachment of chromatin to nuclear compartments or steric impairment caused by local ultrastructure", "A number of these proteins accumulate in viral replication compartments in the infected cell nucleus, indicating that these proteins may have a role in viral replication. ", "Nuclear marginalization of host cell chromatin associated with expansion of two discrete virus-induced subnuclear compartments during baculovirus infection", "In the late stage of infection, however, the peristromal region (PR), another virus-induced subnuclear compartment, was also excluded from the chromatin-localizing area.", "This correlation between compartmentalization and chromatin exclusion suggests the possibility that a chromatin-exclusive property of viral molecules, at least in part, supports nuclear compartmentalization of virus-infected cells.", "Chromatin modifications in hematopoietic multipotent and committed progenitors are independent of gene subnuclear positioning relative to repressive compartments", "To further clarify the contribution of nuclear architecture in the regulation of gene expression patterns during differentiation of human multipotent cells, we analyzed expression status, histone modifications, and subnuclear positioning relative to repressive compartments, of hematopoietic loci in multipotent and lineage-committed primary human hematopoietic progenitors.", "We report here that positioning of lineage-affiliated loci relative to pericentromeric heterochromatin compartments (PCH) is identical in multipotent cells from various origins and is unchanged between multipotent and lineage-committed hematopoietic progenitors. ", "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments.", "Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments.", "Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements,", "we find that architectural compartments are maintained in noncycling mouse thymocytes after genetic depletion of cohesin in vivo", "Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within preexisting chromosomal compartments", "Histone posttranslational modifications mediate establishment of structurally and functionally distinct chromatin compartments of eukaryotic nuclei.", "Recent studies employing chromatin conformation capture techniques indicate that Hox clusters adopt a remarkable spatial configuration, in which active and inactive genes are segregated into two distinct chromatin compartments.", "Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains.", "Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment.", "We propose that basically three nuclear compartments exist, an &quot;open&quot; higher-order chromatin compartment with chromatin domains containing active genes, a &quot;closed&quot; chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al., 1993; Zirbel et al., 1993) that contains macromolecular complexes for transcription, splicing, DNA replication, and repair. Genes in &quot;open,&quot; but not in &quot;closed&quot; higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment.", "Genes in &quot;open,&quot; but not in &quot;closed&quot; higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment. Chromatin domains that build the &quot;open&quot; chromatin compartment are organized in a way that allows the direct contact of genes and nascent RNA to transcription and splicing complexes, respectively, preformed in the ICD compartment.", "We propose that basically three nuclear compartments exist, an &quot;open&quot; higher-order chromatin compartment with chromatin domains containing active genes, a &quot;closed&quot; chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15791412", "http://www.ncbi.nlm.nih.gov/pubmed/18974210", "http://www.ncbi.nlm.nih.gov/pubmed/21637796", "http://www.ncbi.nlm.nih.gov/pubmed/15140983", "http://www.ncbi.nlm.nih.gov/pubmed/22198682", "http://www.ncbi.nlm.nih.gov/pubmed/11909528", "http://www.ncbi.nlm.nih.gov/pubmed/9636146", "http://www.ncbi.nlm.nih.gov/pubmed/9291094", "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "http://www.ncbi.nlm.nih.gov/pubmed/9587055", "http://www.ncbi.nlm.nih.gov/pubmed/18434402", "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "http://www.ncbi.nlm.nih.gov/pubmed/11186332" ]

[]

[]

[ "No. Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells." ]

[ "no" ]

[ "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells.", "We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions.", "Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25340765" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "YES" ]

[ "yes" ]

[ "3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect", "In adult rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude and duration of the calcium transient.", "In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium", "The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine", "hese results indicate that the thyroid state influences the time course of the calcium transient and are consistent with the abbreviation in the duration of contraction that is observed in the hyperthyroid state." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19298522", "http://www.ncbi.nlm.nih.gov/pubmed/2428004", "http://www.ncbi.nlm.nih.gov/pubmed/9875761", "http://www.ncbi.nlm.nih.gov/pubmed/9773867" ]

[]

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[ "defence against retroviral infection\ninnate and adaptative immunity\nvesicular trafficking\nneural differentiation\nembryonic development" ]

[ "defence against retroviral infection", "immunity", "vesicular trafficking", "neural differentiation", "embryonic development" ]

[ "monkey TRIM5α SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core", "These properties, which may enhance resistance of TRIM5α to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid", "RIM5α is a retroviral restriction factor, in which the B30.2 (SPRY) and coiled-coil domains cooperate to determine the specificity of TRIM5α-mediated capture of retroviral capsids", "function of the SPRY/B30.2 domain proteins involved in innate immunity", "SPRY domain is a protein interaction module found in 77 murine and ~100 human proteins, and is implicated in important biological pathways, including those that regulate innate and adaptive immunity", "TRIM5α) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses", " TRIM5α recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner", "binding of the PRY-SPRY domain from the TRIM50 C-terminal region to phosphatidylinositol species, suggesting that TRIM50 is involved in vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids", "TRIM50 seems to play an essential role in tubulovesicular dynamics", "TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis", "TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum", "Vasa coding region is sufficient for its selective enrichment and find that gustavus, the B30.2/SPRY and SOCS box domain gene", "We propose that Gustavus has a conserved, positive regulatory role in Vasa protein accumulation during embryonic development", "two zebrafish genes, SSB-1 and SSB-4 (SPRY domain SOCS box proteins", "We hypothesize that SSB-4 plays a role in the early development of germ cells", "SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing", "TRIM proteins may be conducive to the convergent evolution of virus-restricting factors.", "SPRY and B30.2 protein domains. Evolution of a component of immune defence", ". The combination of SPRY and PRY to produce B30.2 domains may have been selected and maintained as a component of immune defence", " evolution of primate TRIM5alpha, a gene restricting HIV-1 infection", "The SPRY domain of TRIM5alpha, which may be responsible for recognition of incoming viral capsids showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5alpha in primates might be an innate strategy developed in defending retrovirus infection during primate evolutio", "The results are consistent with a role for TRIM5alpha in innate immunity against retroviruses", "B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha", "primate TRIM5alpha identifies a critical species-specific retroviral restriction domain", "By using functional studies of chimeric TRIM5alpha genes, we show that this patch is generally essential for retroviral restriction and is responsible for most of the species-specific antiretroviral restriction activity", "SPRY protein domain", "Heterozygotes for gus or a deletion including gus produce embryos with fewer pole cells and posterior patterning defects", "SPRY-domain and SOCS-box containing protein, GUSTAVUS." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22337885", "http://www.ncbi.nlm.nih.gov/pubmed/22872646", "http://www.ncbi.nlm.nih.gov/pubmed/17431422", "http://www.ncbi.nlm.nih.gov/pubmed/23886867", "http://www.ncbi.nlm.nih.gov/pubmed/15857996", "http://www.ncbi.nlm.nih.gov/pubmed/23775985", "http://www.ncbi.nlm.nih.gov/pubmed/16648259", "http://www.ncbi.nlm.nih.gov/pubmed/16226405", "http://www.ncbi.nlm.nih.gov/pubmed/23091002", "http://www.ncbi.nlm.nih.gov/pubmed/21035437", "http://www.ncbi.nlm.nih.gov/pubmed/15689398", "http://www.ncbi.nlm.nih.gov/pubmed/19184407", "http://www.ncbi.nlm.nih.gov/pubmed/16313355", "http://www.ncbi.nlm.nih.gov/pubmed/23139046", "http://www.ncbi.nlm.nih.gov/pubmed/12479811" ]

[]

[ "http://www.uniprot.org/uniprot/FBSP1_RAT", "http://www.uniprot.org/uniprot/TRI51_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_DROAN", "http://www.uniprot.org/uniprot/CMYA5_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_DROMO", "http://www.uniprot.org/uniprot/BSPRY_HUMAN", "http://www.uniprot.org/uniprot/SPRY7_BOVIN", "http://www.uniprot.org/uniprot/SPRY7_RAT", "http://www.uniprot.org/uniprot/FBSP1_AEDAE", "http://www.uniprot.org/uniprot/FBSP1_DROPE", "http://www.uniprot.org/uniprot/RSPRY_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_ANOGA", "http://www.uniprot.org/uniprot/FBSP1_BRUMA", "http://www.uniprot.org/uniprot/FBSP1_XENLA", "http://www.uniprot.org/uniprot/FBSP1_DROGR", "http://www.uniprot.org/uniprot/SPRY3_PONAB", "http://www.uniprot.org/uniprot/FSD1_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_HUMAN", "http://www.uniprot.org/uniprot/SPRY3_HUMAN", "http://www.uniprot.org/uniprot/SPSB1_BOVIN", "http://www.uniprot.org/uniprot/SPRY4_RAT", "http://www.uniprot.org/uniprot/SPRY7_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_DROSE", "http://www.uniprot.org/uniprot/SPRY7_CHICK", "http://www.uniprot.org/uniprot/SPRY7_HUMAN", "http://www.uniprot.org/uniprot/FSD2_MOUSE", "http://www.uniprot.org/uniprot/RSPRY_MACFA", "http://www.uniprot.org/uniprot/FBSP1_CAEBR", "http://www.uniprot.org/uniprot/SPRY4_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_MOUSE", "http://www.uniprot.org/uniprot/FSD1_DANRE", "http://www.uniprot.org/uniprot/SPSB1_HUMAN", "http://www.uniprot.org/uniprot/BSPRY_MOUSE", "http://www.uniprot.org/uniprot/BSPRY_RAT", "http://www.uniprot.org/uniprot/SPRY4_HUMAN" ]

[ "The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, based on the observation that related proteins in one organism (including physically interacting proteins/members of complexes, proteins involved in the same pathway) tend to be found in other species as a fused composite gene encoding a single multifunctional protein. For this purpose, gene fusion events may be used as the sole evidence or as independent information combined with other 'genome-aware' or similarity-based methods, and functional association may be predicted at different levels. An advantage of this approach is that it is not necessary to know the function of the composite/components to infer association." ]

[]

[ "Gene fusion is an important evolutionary process. It can yield valuable information to infer the interactions and functions of proteins.", "We have developed a Bayesian framework to infer phosphorylation networks from time series measurements of phosphosite concentrations upon ligand stimulation. To increase the prediction accuracy we integrated different types of data, e.g., amino acid sequence data, genomic context data (gene fusion, gene neighborhood, and phylogentic profiles)", "It is assumed that two proteins, which are found to be transcribed by a single transcript in one (or several) genomes are likely to be functionally linked, for example by acting in a same metabolic pathway or by forming a multiprotein complex. This method is of particular interest for studying genes that exhibit no, or only remote, homologies with already well-characterized proteins.", "PLEX search results are accompanied by quantitative estimates of linkage confidence, enabling users to take advantage of coinheritance, operon and gene fusion-based methods for inferring gene function and reconstructing cellular systems and pathways.", "While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships.", "detection of gene fusion events can contribute towards the elucidation of functional associations of proteins within entire genomes", "Inference of gene function based on gene fusion events: the rosetta-stone method.", "protein domain fusions in human protein interaction networks prediction", "Some proteins, involved in a common biological process and encoded by separate genes in one organism, can be found fused within a single protein chain in other organisms. By detecting these triplets, a functional relationship can be established between the unfused proteins.", "These results suggest that domain fusion is an appropriate method for predicting protein complexes.", "The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, including physical interactions or complex formation.", "These genomic constraints form the basis for a variety of techniques that employ systematic genome comparisons to predict functional associations among genes. The most powerful techniques to date are based on conserved gene neighborhood, gene fusion events, and common phylogenetic distributions of gene families", "Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events.", "Genes linked by fusion events are generally of the same functional category", "a functional association between two genes can be derived from the existence of a fusion of the two as one continuous sequence in another genome", "Protein interaction maps for complete genomes based on gene fusion events", "Because there must be selective pressure for certain genes to be fused over the course of evolution, we are able to predict functional associations of proteins.", "We observed that gene fusion events are more related to physical interaction between proteins than to other weaker functional relationships such as participation in a common biological pathway.", "FusionDB provides a characterization of a large number of gene fusion events at hand of multiple sequence alignments.", "Domain fusion analysis has been proposed recently to infer the functional association of the component proteins.", "Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19582169", "http://www.ncbi.nlm.nih.gov/pubmed/15980440", "http://www.ncbi.nlm.nih.gov/pubmed/16571130", "http://www.ncbi.nlm.nih.gov/pubmed/11438739", "http://www.ncbi.nlm.nih.gov/pubmed/15215406", "http://www.ncbi.nlm.nih.gov/pubmed/22267904", "http://www.ncbi.nlm.nih.gov/pubmed/12095249", "http://www.ncbi.nlm.nih.gov/pubmed/15701682", "http://www.ncbi.nlm.nih.gov/pubmed/18546511", "http://www.ncbi.nlm.nih.gov/pubmed/22161322", "http://www.ncbi.nlm.nih.gov/pubmed/21729286", "http://www.ncbi.nlm.nih.gov/pubmed/17767732", "http://www.ncbi.nlm.nih.gov/pubmed/20532224", "http://www.ncbi.nlm.nih.gov/pubmed/18629289", "http://www.ncbi.nlm.nih.gov/pubmed/23220349", "http://www.ncbi.nlm.nih.gov/pubmed/12429063", "http://www.ncbi.nlm.nih.gov/pubmed/14673105", "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "http://www.ncbi.nlm.nih.gov/pubmed/16221304", "http://www.ncbi.nlm.nih.gov/pubmed/15128449", "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "http://www.ncbi.nlm.nih.gov/pubmed/17597916", "http://www.ncbi.nlm.nih.gov/pubmed/12952538", "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "http://www.ncbi.nlm.nih.gov/pubmed/11178267", "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "http://www.ncbi.nlm.nih.gov/pubmed/12519996", "http://www.ncbi.nlm.nih.gov/pubmed/11820254", "http://www.ncbi.nlm.nih.gov/pubmed/12429059", "http://www.ncbi.nlm.nih.gov/pubmed/12049665", "http://www.ncbi.nlm.nih.gov/pubmed/15960802", "http://www.ncbi.nlm.nih.gov/pubmed/22925561", "http://www.ncbi.nlm.nih.gov/pubmed/11864366", "http://www.ncbi.nlm.nih.gov/pubmed/18081932", "http://www.ncbi.nlm.nih.gov/pubmed/16381848" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050939" ]

[ "The protein NONO forms heterodimers with PSPC1, SFPQ." ]

[ "PSPC1", "SFPQ" ]

[ "The paraspeckle component 1 (PSPC1) and non-POU-domain-containing octamer-binding protein (NONO) heterodimer is an essential structural component of paraspeckles,", "PSPC1-NONO heterodimer.", "Crystallization of a paraspeckle protein PSPC1-NONO heterodimer", "difficult heterodimeric complex of two human proteins, paraspeckle component 1 (PSPC1) and non-POU domain-containing octamer-binding protein (NONO), that are involved in gene regulation and the structural integrity of nuclear bodies termed paraspeckles is described.", "SFPQ (PSF) and NONO (p54) are nuclear proteins that interact with each other and have diverse roles in nucleic acids metabolism. The SFPQ/NONO heterodimer was previously found to enhance DNA strand break rejoining in vitro.", "We identified a heterodimer, p54nrb and PSF,", "P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner.", "e demonstrated that the PSF heterodimer partner, p54nrb (non-POU-domain-containing, octamer binding protein), can also function as a transcription corepressor, independent of PSF.", "The PSPC1/NONO heterodimer has a right-handed antiparallel coiled-coil", "Structure of the heterodimer of human NONO and paraspeckle protein component 1" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16148043", "http://www.ncbi.nlm.nih.gov/pubmed/22101825", "http://www.ncbi.nlm.nih.gov/pubmed/22102035", "http://www.ncbi.nlm.nih.gov/pubmed/20421735", "http://www.ncbi.nlm.nih.gov/pubmed/18655028", "http://www.ncbi.nlm.nih.gov/pubmed/19423654", "http://www.ncbi.nlm.nih.gov/pubmed/22416126" ]

[]

[ "http://www.uniprot.org/uniprot/NONO_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043497", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019281", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055503", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046982" ]

[ "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome." ]

[ "Robinow syndrome" ]

[ "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome.", "Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals.", "DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.", "argeted Sanger sequencing in additional subjects with DRS uncovered DVL1 exon 14 mutations in five individuals, including a pair of monozygotic twins." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "http://www.ncbi.nlm.nih.gov/pubmed/25817016" ]

[]

[]

[ "Yes, several compounds that inhibit different members of the proteasome pathway (for example Bortezomib) are on trial for treatment of leukemia and solid tumors. It seems that a combination with other drugs may be a useful therapy for solid tumors." ]

[ "yes" ]

[ "We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target", "We further found that ATO targets AME via both myelodysplastic syndrome 1 (MDS1) and EVI1 moieties and degrades EVI1 via the ubiquitin-proteasome pathway and MDS1 in a proteasome-independent manner. Our results suggest that ATO could be used as a part of targeted therapy for AME-, AML1/MDS1-, MDS1/EVI1-, and EVI1-positive human cancers.", "Previously we had shown the synergic effect of bortezomib and thiostrepton in breast cancer cells in vitro, where sub-apoptotic concentrations of both proteasome inhibitors resulted in synergic increase in cell death when combined as a treatment. Here, we administered such a combination to MDA-MB-231 xenograft tumors in vivo, and found that the effect of complementary proteasome inhibitors reduced tumor growth rates more efficiently than compared with when administered alone.", "Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer.", "Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications.", "Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC", "Our study indicates a molecular mechanism by which the sensitivity of thyroid cancer cells is regulated by the level of GRP78 as well as preferential induction of GRP78 or CHOP upon treatment with proteasome inhibitors. Our experiments therefore suggest a novel approach toward sensitization of thyroid cancer cells to proteasome inhibitors.", "Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity.", "The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib.", "Given the results of this trial, it is safe and reasonable to recommend treatment with PS341 on the schedule used in this trial at 1.56 mg/m2/dose in Phase II trials. Particular care should be taken with patients with preexisting neuropathy", "The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia", "Such efforts have led to bortezomib, the first FDA approved proteasome inhibitor now used as a frontline treatment for newly diagnosed multiple myeloma (MM), relapsed/refractory MM and mantle cell lymphoma", "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22057347", "http://www.ncbi.nlm.nih.gov/pubmed/17145882", "http://www.ncbi.nlm.nih.gov/pubmed/22012631", "http://www.ncbi.nlm.nih.gov/pubmed/15169797", "http://www.ncbi.nlm.nih.gov/pubmed/20160034", "http://www.ncbi.nlm.nih.gov/pubmed/20219102", "http://www.ncbi.nlm.nih.gov/pubmed/19712963", "http://www.ncbi.nlm.nih.gov/pubmed/17431003", "http://www.ncbi.nlm.nih.gov/pubmed/19821999", "http://www.ncbi.nlm.nih.gov/pubmed/22134540", "http://www.ncbi.nlm.nih.gov/pubmed/23477519", "http://www.ncbi.nlm.nih.gov/pubmed/16135477", "http://www.ncbi.nlm.nih.gov/pubmed/23181572", "http://www.ncbi.nlm.nih.gov/pubmed/22353937", "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "http://www.ncbi.nlm.nih.gov/pubmed/12171876" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061988", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007938" ]

[ "Yes. CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. Absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion." ]

[ "yes" ]

[ "Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring", "These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks. The ring-shaped cohesin complex is loaded onto chromosomes before S phase in an ATP hydrolysis-dependent reaction. Cohesion establishment during DNA replication follows without further cohesin recruitment and without need for cohesin to re-engage an ATP hydrolysis motif that is critical for its initial DNA binding. This provides evidence for cohesion establishment in the context of replication forks and imposes constraints on the mechanism involved", "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II", "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis", "We also show that, in contrast to mitosis, RF-C(Ctf18/Dcc1/Cft8), Ctf4 and Chl1 are essential for chromosome segregation during meiosis and for the viability of meiotic products.", "Ctf8p is a component of Ctf18-RFC, an alternative replication factor C-like complex required for efficient sister chromatid cohesion in Saccharomyces cerevisiae. We performed synthetic genetic array (SGA) analysis with a ctf8 deletion strain as a primary screen to identify other nonessential genes required for efficient sister chromatid cohesion. We then assessed proficiency of cohesion at three chromosomal loci in strains containing deletions of the genes identified in the ctf8 SGA screen. Deletion of seven genes (CHL1, CSM3, BIM1, KAR3, TOF1, CTF4, and VIK1) resulted in defective sister chromatid cohesion", "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion", "CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion.", "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.", "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.", "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks", "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion", "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint", "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19430531", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/14742714", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/23036200" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045876", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007062", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007063" ]

[ "Genomic Regions Enrichment of Annotations Tool (GREAT) is a tool to analyse the functional significance of cis-regulatory regions identified by localised measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, many functions of these factors are recovered that are missed by existing gene-based tools, and testable hypotheses are generated. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets." ]

[]

[ "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions", " GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, we recover many functions of these factors that are missed by existing gene-based tools, and we generate testable hypotheses. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets", "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome.", "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome", "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. ", " We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions.", "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20436461" ]

[]

[]

[ "The drug Olaparib target the protein poly(ADP-ribose) polymerase." ]

[ "poly(ADP-ribose) polymerase", "PARP" ]

[ "We show that targeting PARP by the small molecule inhibitors, Olaparib ", "Following treatment with the PARP1 inhibitor olaparib, ", "the PARP inhibitor olaparib", "Olaparib (AZD-2281, Ku-0059436) is an orally bioavailable and well-tolerated poly(ADP-ribose) polymerase (PARP) inhibitor currently under investigation in patients with solid tumors.", "The poly(ADP-ribose) polymerase inhibitor olaparib", "olaparib (poly(ADP ribose)polymerase inhibitor)", " olaparib, a PARP inhibitor, ", "Olaparib is an oral poly (ADP-ribose) polymerase inhibitor", "olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. ", "he poly (ADP-ribose) polymerase inhibitor olaparib ", " PARP-inhibitor, Olaparib", "Olaparib is a poly(ADP-ribose) polymerase inhibitor", "olaparib, a specific PARP1 inhibitor.", "PARP inhibitor olaparib ", "We used two PARP inhibitors in clinical development, olaparib and rucaparib", " the PARPi, olaparib, " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25120693", "http://www.ncbi.nlm.nih.gov/pubmed/25221646", "http://www.ncbi.nlm.nih.gov/pubmed/25526472", "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "http://www.ncbi.nlm.nih.gov/pubmed/25417706", "http://www.ncbi.nlm.nih.gov/pubmed/25275045", "http://www.ncbi.nlm.nih.gov/pubmed/25302833", "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "http://www.ncbi.nlm.nih.gov/pubmed/25531448", "http://www.ncbi.nlm.nih.gov/pubmed/25218906", "http://www.ncbi.nlm.nih.gov/pubmed/25128455", "http://www.ncbi.nlm.nih.gov/pubmed/25481791", "http://www.ncbi.nlm.nih.gov/pubmed/25144364", "http://www.ncbi.nlm.nih.gov/pubmed/25483710", "http://www.ncbi.nlm.nih.gov/pubmed/25139258", "http://www.ncbi.nlm.nih.gov/pubmed/25374341" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "C71721" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls/label/A17696481" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "Olaparib" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls/label/A17682038" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "PARP Inhibitor AZD2281" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "C71721" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#inScheme", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls" } ]

[ "http://www.uniprot.org/uniprot/PARP_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042493", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.uniprot.org/uniprot/PARP_SARPE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011065" ]

[ "The lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH" ]

[ "yes" ]

[ "This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TRα1.", "Here we show that the dysregulation of the pituitary-thyroid axis was worsened by the lack of TR alpha1 in TR betaPV mice, and severe impairment of postnatal growth was manifested in TR betaPV mice deficient in TR alpha1.", "Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. ", "The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment.", "No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality", "These results demonstrate that the lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23633213", "http://www.ncbi.nlm.nih.gov/pubmed/17906375", "http://www.ncbi.nlm.nih.gov/pubmed/7913092", "http://www.ncbi.nlm.nih.gov/pubmed/9092799", "http://www.ncbi.nlm.nih.gov/pubmed/17040361", "http://www.ncbi.nlm.nih.gov/pubmed/7711514", "http://www.ncbi.nlm.nih.gov/pubmed/8068885", "http://www.ncbi.nlm.nih.gov/pubmed/15988389", "http://www.ncbi.nlm.nih.gov/pubmed/12750454", "http://www.ncbi.nlm.nih.gov/pubmed/9685218", "http://www.ncbi.nlm.nih.gov/pubmed/8594618", "http://www.ncbi.nlm.nih.gov/pubmed/9350446", "http://www.ncbi.nlm.nih.gov/pubmed/8954015", "http://www.ncbi.nlm.nih.gov/pubmed/8115332", "http://www.ncbi.nlm.nih.gov/pubmed/8384535", "http://www.ncbi.nlm.nih.gov/pubmed/15860414", "http://www.ncbi.nlm.nih.gov/pubmed/8475937", "http://www.ncbi.nlm.nih.gov/pubmed/12356724", "http://www.ncbi.nlm.nih.gov/pubmed/15913586" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018382", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.disease-ontology.org/api/metadata/DOID:11633", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988" ]

[ "In urinary bladder cancer, RhoA was more commonly found to be activated in the later stages of the disease. This activation was related to poor tumor differentiation, muscle invasion, lymph node metastasis, and shortened disease-free and overall survival." ]

[]

[ "Alterations in RhoA, RhoB, RhoC, Rac1 and Cdc42 expression play a significant role in the genesis and progression of UCC of the urinary bladder.", "Published reports suggest that elevated RhoA/Rho-kinase signaling plays a role in the development of benign prostatic hyperplasia, erectile dysfunction, kidney failure, ejaculation disorders, prostate and bladder cancer initiation, and eventual metastasis.", "The suppressive effect of Rho kinase inhibitor, Y-27632, on oncogenic Ras/RhoA induced invasion/migration of human bladder cancer TSGH cells", "Our results provide evidence that Ras-induced RhoA and NF-kappaB activation was involved in the invasion/migration of bladder cancer.", "Increased RHOA expression was more common in grade 3 than in grade 2 tumors (P = 0.016).", "RhoA, RhoC, and ROCK were more abundant in tumors and metastatic lymph nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001).", "High RhoA, RhoC, and ROCK expression were related to poor tumor differentiation (P < 0.05, P < 0.01, and P < 0.01, respectively), muscle invasion (P < 0.001), and lymph node metastasis (P < 0.05).", "Kaplan-Meier plots linked high RhoA, RhoC, and ROCK protein expression to shortened disease-free and overall survival (P < 0.0001).", "By univariate analysis, high RhoA, RhoC, and ROCK protein expression predicted shortened disease-free and overall survival (P < 0.0001).", "Overall survival in tumors invading muscle (T2 to T4; 44 patients) was significantly influenced by RhoA, RhoC, and ROCK in a Kaplan-Meier analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19896475", "http://www.ncbi.nlm.nih.gov/pubmed/21054792", "http://www.ncbi.nlm.nih.gov/pubmed/18190825", "http://www.ncbi.nlm.nih.gov/pubmed/22006759", "http://www.ncbi.nlm.nih.gov/pubmed/12855641" ]

[]

[ "http://www.uniprot.org/uniprot/RHOA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001749", "http://www.disease-ontology.org/api/metadata/DOID:4007", "http://www.disease-ontology.org/api/metadata/DOID:11054", "http://www.disease-ontology.org/api/metadata/DOID:7371" ]

[ "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. ", "An assay for transposase-accessible chromatin using sequencing (ATAC-seq) is based on in vitro transposition of sequencing adaptors into native chromatin. It is described as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution." ]

[]

[ "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.", "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis.", "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.", "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ", "When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted regions or accessible/open chromatin. Here we ask whether open chromatin profiling can be used to identify the entire repertoire of active promoters and enhancers underlying tissue-specific gene expression during normal development and oncogenesis in vivo. To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. ", "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "http://www.ncbi.nlm.nih.gov/pubmed/25679813" ]

[]

[]

[ "GAC\nSHMT2\nAMPAR\nOrai1\nOrai3" ]

[ "GAC", "SHMT2", "AMPAR", "Orai1", "Orai3" ]

[ " the ability of GAC to undergo the dimer-to-tetramer transition necessary for enzyme activation.", "while SHMT2 undergoes a dimer-to-tetramer transition upon PLP binding.", "AMPARs that is required for the critical dimer-to-tetramer transition.", "We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB.", "the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23739980", "http://www.ncbi.nlm.nih.gov/pubmed/21080238", "http://www.ncbi.nlm.nih.gov/pubmed/25548170", "http://www.ncbi.nlm.nih.gov/pubmed/25619277", "http://www.ncbi.nlm.nih.gov/pubmed/21987805" ]

[]

[]

[ "Inhibition of sodium glucose co-transporter 2 (SGLT2) is the major mechanism of action of canagliflozin. Canagliflozin is the first SGLT2 inhibitor to be approved in the USA for the treatment of type 2 diabetes and is under regulatory review in the EU. Other SGLT2 inhibitors include dapagliflozin and empagliflozin." ]

[ "sodium glucose co-transporter 2" ]

[ "During the past year, two SGLT2 inhibitors, canagliflozin and dapagliflozin, have been approved for the treatment of type 2 diabetes.", "Currently dapagliflozin, one of the three most advanced SGLT2 inhibitors in the development (along with canagliflozin and empagliflozin), is already in the market in few European countries and canagliflozin has been approved from the Food and Drug Administration (FDA) in US.", "Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2 diabetes mellitus.", "This report reviews the potentially beneficial effects of SGLT2 inhibitors in type 2 diabetes mellitus, specifically focusing on canagliflozin, the only SGLT2 inhibitor approved for use in the United States.", "The sodium glucose co-transporter 2 inhibitor canagliflozin lowered blood glucose, blood pressure, and body weight, with increased risk of urogenital infections in Phase 2 studies. ", "Canagliflozin (Invokana™), an oral selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is under global development with Mitsubishi Tanabe Pharma and Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, for the treatment of type 2 diabetes mellitus.", "Canagliflozin is the first SGLT2 inhibitor to be approved in the USA and is under regulatory review in the EU. ", "Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus.", "Canagliflozin is an orally administered sodium glucose cotransporter 2 inhibitor proposed for the treatment of type 2 diabetes.", "In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin.", "Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. ", "Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24040872", "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "http://www.ncbi.nlm.nih.gov/pubmed/22621689", "http://www.ncbi.nlm.nih.gov/pubmed/21680987", "http://www.ncbi.nlm.nih.gov/pubmed/23895803", "http://www.ncbi.nlm.nih.gov/pubmed/23590413", "http://www.ncbi.nlm.nih.gov/pubmed/24257692", "http://www.ncbi.nlm.nih.gov/pubmed/23087012", "http://www.ncbi.nlm.nih.gov/pubmed/23326927", "http://www.ncbi.nlm.nih.gov/pubmed/10481836", "http://www.ncbi.nlm.nih.gov/pubmed/23563279", "http://www.ncbi.nlm.nih.gov/pubmed/23042029", "http://www.ncbi.nlm.nih.gov/pubmed/23412078", "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "http://www.ncbi.nlm.nih.gov/pubmed/22547464" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051051", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032410", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ]

[ "Altered thyroid profile, particularly sick euthyroid syndrome, is an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters." ]

[]

[ " Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide", "The T3 was more meaningful than the BNP in the prognosis of CHF. The BNP and T3 combination detection was more valuable in determining the severity of CHF and prognosis.", "fT3 and BNP hold an independent and additive prognostic value in HF.", "Univariate regression analysis showed that TSH (p<0.0001), fT3 (p<0.0001), fT4 (p=0.016) and fT3/fT4 (p<0.0001) were associated with heart failure progression but multivariate analysis showed that only TSH considered as a continuous variable (p = 0.001) as well as subclinical hypothyroidism (TSH > 5.5 mUI/l; p=0.014) remained significantly associated with the events.", "Low T(3) levels are an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters.", "Sixteen patients (14%) died during the follow-up period; their fT3/fT4 ratio was significantly lower than the patients who survived (1.31+/-0.37 vs. 2.01+/-0.72, p<0.001).", "The authors conclude that among elderly patients with heart failure, lower triiodothyronine concentrations are more prevalent and are associated with a worse prognosis.", "A low free T3 index/reverse T3 ratio is associated with poor ventricular function and nutritional status and is the strongest predictor yet identified for short-term outcome in patients with advanced heart failure." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15259379", "http://www.ncbi.nlm.nih.gov/pubmed/12963854", "http://www.ncbi.nlm.nih.gov/pubmed/17315395", "http://www.ncbi.nlm.nih.gov/pubmed/15694896", "http://www.ncbi.nlm.nih.gov/pubmed/2189307", "http://www.ncbi.nlm.nih.gov/pubmed/20024637", "http://www.ncbi.nlm.nih.gov/pubmed/19110971", "http://www.ncbi.nlm.nih.gov/pubmed/18221125", "http://www.ncbi.nlm.nih.gov/pubmed/22870736", "http://www.ncbi.nlm.nih.gov/pubmed/23369135", "http://www.ncbi.nlm.nih.gov/pubmed/19181292", "http://www.ncbi.nlm.nih.gov/pubmed/2358611", "http://www.ncbi.nlm.nih.gov/pubmed/16499159", "http://www.ncbi.nlm.nih.gov/pubmed/15642542", "http://www.ncbi.nlm.nih.gov/pubmed/19917524", "http://www.ncbi.nlm.nih.gov/pubmed/8333797", "http://www.ncbi.nlm.nih.gov/pubmed/17966446", "http://www.ncbi.nlm.nih.gov/pubmed/8960429", "http://www.ncbi.nlm.nih.gov/pubmed/23435988", "http://www.ncbi.nlm.nih.gov/pubmed/17923583", "http://www.ncbi.nlm.nih.gov/pubmed/20978564", "http://www.ncbi.nlm.nih.gov/pubmed/12165115", "http://www.ncbi.nlm.nih.gov/pubmed/23555069", "http://www.ncbi.nlm.nih.gov/pubmed/9489964", "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "http://www.ncbi.nlm.nih.gov/pubmed/19006851" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:9651", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ]

[ "The following mutations of the phospholamban gene have been found to be associated with hypertrophic cardiomyopathy: PLN L39X nonsense mutation; PLN Leu39Ter; PLN -42 C>G and PLN -77A-->G" ]

[ "PLN L39X nonsense mutation", "PLN Leu39Ter", "PLN -42 C>G", "PLN -77A-->G" ]

[ "one L39X nonsense mutation was identified in 1 of 1,064 HCM proband cases with a family history of HCM, previously found to be negative for the current HCM genetic test panel. This mutation cosegregated with incidence of HCM in a multigenerational family.", "The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy. ", "The PLN -42 C>G mutation is associated with a benign form of apical hypertrophic cardiomyopathy in this family, though the presence of a healthy adult carrier suggests that other genetic and environmental factors could be involved. ", "We found a heterozygous single nucleotide transition from A to G at -77-bp upstream of the transcription start site in the phospholamban promoter region of one patient with familial hypertrophic cardiomyopathy.", "Using neonatal rat cardiomyocytes, the mutation, -77A-->G, increased the phospholamban promoter activity. No nucleotide change in the phospholamban coding region was found in 99 patients with cardiomyopathy. We suspect that the mutation plays an important role in the development of hypertrophic cardiomyopathy.", "Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17655857", "http://www.ncbi.nlm.nih.gov/pubmed/21167350", "http://www.ncbi.nlm.nih.gov/pubmed/16829191", "http://www.ncbi.nlm.nih.gov/pubmed/12705874" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ]