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[ "There is evidence to suggest that adiponectin plays a role in migraine. Increase in body fat elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk. In episodic migraine patients, adiponectin was associated with migraine severity and predictive of acute treatment response. Serum adiponectin levels are increased in women chronic daily headache sufferers." ]

[]

[ "Increase in body fat, especially in gluteofemoral region, elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk.", "CONCLUSION: In this pilot study of women episodic migraineurs, the HMW : LMW ADP ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW : LMW ratio of ADP represent potential novel biomarkers and drug targets for episodic migraine.", "Specifically, neurotransmittors such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin have been suggested to have roles in both feeding and migraine. ", "Obesity can be considered as a proinflammatory state in which increased inflammatory mediators, vascular hyperreactivity, plasma calcitonin gene-related peptide (CGRP) concentrations and decreased adiponectin concentrations are observed. These alterations can cause an increase in the frequency of migraine attacks developed of central sensitization, and thereafter, chronic migraine.", "Specifically, neurotransmittors such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin have been suggested to have roles in both feeding and migraine. ", "Several adipocytokines appear to play an integral role in feeding and obesity--and have also been linked to pain. Among these proteins are adiponectin and leptin. The author reviews the regulation of adipose tissue and feeding and provides an in-depth examination of adiponectin and leptin and their association with migraine.", "CONCLUSION: Serum adiponectin levels are increased in women chronic daily headache (CDH) sufferers.", "n this review we discuss the basic science of adiponectin and its potential connection to the pathophysiology of migraine. Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.", "Collectively, the results of our analysis suggest that a link between serum adiponectin and migraine remains elusive, at the best", "Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24648004", "http://www.ncbi.nlm.nih.gov/pubmed/18474846", "http://www.ncbi.nlm.nih.gov/pubmed/19556389", "http://www.ncbi.nlm.nih.gov/pubmed/24819919", "http://www.ncbi.nlm.nih.gov/pubmed/19845784", "http://www.ncbi.nlm.nih.gov/pubmed/17448181", "http://www.ncbi.nlm.nih.gov/pubmed/20200812", "http://www.ncbi.nlm.nih.gov/pubmed/19882941", "http://www.ncbi.nlm.nih.gov/pubmed/24820828", "http://www.ncbi.nlm.nih.gov/pubmed/23489216", "http://www.ncbi.nlm.nih.gov/pubmed/25378672", "http://www.ncbi.nlm.nih.gov/pubmed/24250893", "http://www.ncbi.nlm.nih.gov/pubmed/22823862", "http://www.ncbi.nlm.nih.gov/pubmed/17515549" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:6364", "http://www.uniprot.org/uniprot/ADIPO_HUMAN", "http://www.uniprot.org/uniprot/ADIPO_MOUSE", "http://www.uniprot.org/uniprot/ADIPO_BOVIN" ]

[ " Oncogene addiction describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that addiction may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call oncogenic shock, prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death. ", "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. \"Addiction\" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call \"oncogenic shock,\" prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death." ]

[]

[ "Tumor cell growth and survival can often be impaired by inactivating a single oncogen- a phenomenon that has been called as \"oncogene addiction.\" It is in such scenarios that molecular targeted therapies may succeed.", "The clinical efficacy of tyrosine kinase inhibitors supports the dependence of distinct subsets of cancers on specific driver mutations for survival, a phenomenon called \"oncogene addiction.", "A given tumor is usually dependent on the oncogene that is activated in the respective tumor entity. This phenomenon called oncogene addiction provides the rationale for attempts to target oncogene products in a therapeutic manner, be it by small molecules, by small interfering RNAs (siRNA) or by antigen-specific T cells.", "It has long been established that cancers can become addicted to particular oncogenes. Despite the genetic complexity that governs tumorigenesis, certain cancers can exhibit a critical dependency on the expression of a single oncogene, which when removed leads to death of the cancer cell. ", "We now know that oncogenes are dysfunctional proto-oncogenes and that dysfunctional tumor suppressor genes contribute to the cancer process. Furthermore, Weinstein and others have hypothesized the phenomenon of oncogene addiction as a distinct characteristic of the malignant cell. It can be assumed that cancer cells, indeed, become dependent on such vital oncogenes. The products of these vital oncogenes, such as c-myc, may well be the Achilles heel by which targeted molecular therapy may lead to truly personalized cancer therapy.", "Despite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiological activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction. Oncogene addiction had been thought to occur largely through tumour cell-autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence. ", "Cancers can exhibit marked tumor regression after oncogene inhibition through a phenomenon called \"oncogene addiction.\" The ability to predict when a tumor will exhibit oncogene addiction would be useful in the development of targeted therapeutics. Oncogene addiction is likely the consequence of many cellular programs. However, we reasoned that many of these inputs may converge on aggregate survival and death signals.", "The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction.", "Although human cancers have complex genotypes and are genomically unstable, they often remain dependent on the continued presence of single-driver mutations-a phenomenon dubbed \"oncogene addiction.\" Such dependencies have been demonstrated in mouse models, where conditional expression systems have revealed that oncogenes able to initiate cancer are often required for tumor maintenance and progression, thus validating the pathways they control as therapeutic targets.", "Oncogene addiction is a phenomenon that the survival of cancer cells depends on an activated oncogene or inactivation of tumor suppressor gene, and is regarded as the 'Achilles heel' of the successful molecular targeted therapies in cancer.", "Inhibition of an initiating oncogene often leads to extensive tumour cell death, a phenomenon known as oncogene addiction. This has led to the search for compounds that specifically target and inhibit oncogenes as anticancer agents.", "Cancer is a multistep process whereby genetic events that result in the activation of proto-oncogenes or the inactivation of tumor suppressor genes usurp physiologic programs mandating relentless proliferation and growth. Experimental evidence surprisingly illustrates that the inactivation of even a single oncogene can be sufficient to induce sustained tumor regression. These observations suggest the hypothesis that tumors become irrevocably addicted to the oncogenes that initiated tumorigenesis. The proposed explanation for this phenomenon is that activated oncogenes result in a signaling state in which the sudden abatement of oncogene activity balances towards proliferative arrest and apoptosis. Indeed, substantial evidence supports this hypothesis.", "Cancer cells contain multiple genetic and epigenetic abnormalities. Despite this complexity, their growth and survival can often be impaired by the inactivation of a single oncogene. This phenomenon, called \"oncogene addiction,\" provides a rationale for molecular targeted therapy.", "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction. We assemble here the evidence that oncogene addiction is angiogenesis-dependent.", "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that \"addiction\" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call \"oncogenic shock,\" prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death.", "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction.", "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies.", "Oncogene addiction is a phenomenon that the survival of cancer cells depends on an activated oncogene or inactivation of tumor suppressor gene, and is regarded as the Achilles heel of the successful molecular targeted therapies in cancer.", "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies", "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22860051", "http://www.ncbi.nlm.nih.gov/pubmed/20173739", "http://www.ncbi.nlm.nih.gov/pubmed/21974937", "http://www.ncbi.nlm.nih.gov/pubmed/22647359", "http://www.ncbi.nlm.nih.gov/pubmed/23532334", "http://www.ncbi.nlm.nih.gov/pubmed/21828272", "http://www.ncbi.nlm.nih.gov/pubmed/22312254", "http://www.ncbi.nlm.nih.gov/pubmed/22235994", "http://www.ncbi.nlm.nih.gov/pubmed/21575270", "http://www.ncbi.nlm.nih.gov/pubmed/18451131", "http://www.ncbi.nlm.nih.gov/pubmed/18451130", "http://www.ncbi.nlm.nih.gov/pubmed/16857816", "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "http://www.ncbi.nlm.nih.gov/pubmed/16869776", "http://www.ncbi.nlm.nih.gov/pubmed/23637683" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009857" ]

[ "Yes. There are < 10 studies reported, answering questions like : how to improve speed of recovery, relationship to dreaming and anesthetic experience, effect on cardiac troponin release, effect on myocardial injury, postoperative delirium, haemodynamics & emergence and recovery characteristics of total intravenous anaesthesia, costs of postoperative nausea and vomiting, pediatric conscious sedation for dental procedures" ]

[ "yes" ]

[ "After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups.", "Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room.", "A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation.", "The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60% (60/100) of the sevoflurane group and 33% (33/100) of the propofol group (P=0.000)", "Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation.", "Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction", "Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study.", "We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery.", "Myocardial injury in remifentanil-based anaesthesia for off-pump coronary artery bypass surgery: an equipotent dose of sevoflurane versus propofol", "This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50.", "This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia.", "Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg", "We compared the haemodynamics, emergence and recovery characteristics of total intravenous anaesthesia using propofol/remifentanil with sevoflurane/remifentanil anaesthesia, under bispectral index guidance, in 103 patients undergoing surgical procedures lasting > 3.5 h", "A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane", "Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment.", "We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups", "In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).", "Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial.", "We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16867087", "http://www.ncbi.nlm.nih.gov/pubmed/21733178", "http://www.ncbi.nlm.nih.gov/pubmed/20683334", "http://www.ncbi.nlm.nih.gov/pubmed/12693995", "http://www.ncbi.nlm.nih.gov/pubmed/23452265", "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "http://www.ncbi.nlm.nih.gov/pubmed/21675061", "http://www.ncbi.nlm.nih.gov/pubmed/15310345", "http://www.ncbi.nlm.nih.gov/pubmed/22103571", "http://www.ncbi.nlm.nih.gov/pubmed/11966554" ]

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[ "http://www.biosemantics.org/jochem#4252326" ]

[ "Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract." ]

[ "epithelial cells" ]

[ "Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract. ", "These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance ", "Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium.", ". Immunohistochemical analysis revealed that gasdermins are expressed specifically in cells at advanced stages of differentiation in the upper epidermis, the differentiating inner root sheath and hair shaft and in the most mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous gland, and anal glands. This expression pattern suggests a role for gasdermins in differentiation of the epidermis and its appendages." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19051310", "http://www.ncbi.nlm.nih.gov/pubmed/23979942", "http://www.ncbi.nlm.nih.gov/pubmed/15737203", "http://www.ncbi.nlm.nih.gov/pubmed/18693275" ]

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[ "Proteins have signal sequences typically resent at the most N-terminal end." ]

[ "N-terminally" ]

[ "A transmembrane domain (TMD) at the N-terminus of a membrane protein is a signal sequence that targets the protein to the endoplasmic reticulum (ER) membrane. ", " an N-terminal signal sequence,", "soluble AMO possesses an N-terminal signal sequence", "n N-terminal \"twin arginine\" signal sequence suggested ", "Proteins destined for the mitochondrial matrix space have leader sequences that are typically present at the most N-terminal end of the nuclear-encoded precursor protein. ", "N-terminal signal sequence ", "The predicted amino-acid sequence includes an N-terminal signal sequence ", "These N-terminal sequences lack a typical signal sequence ", " TAP can be bypassed by targeting peptides directly to the endoplasmic reticulum (ER) using NH2-terminal signal sequences. T", "The amino terminal signal sequence, ", "An amino-terminal domain containing a signal sequence", "A nuclear localization signal (NLS) sequence was previously defined by point mutations in three short adjacent clusters of basic amino acids located in the amino-terminal region of the E1 protein. ", "he human homologue also contains a putative N-terminal signal sequence" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8077949", "http://www.ncbi.nlm.nih.gov/pubmed/12551941", "http://www.ncbi.nlm.nih.gov/pubmed/9624150", "http://www.ncbi.nlm.nih.gov/pubmed/8307567", "http://www.ncbi.nlm.nih.gov/pubmed/8955395", "http://www.ncbi.nlm.nih.gov/pubmed/21834515", "http://www.ncbi.nlm.nih.gov/pubmed/11575719", "http://www.ncbi.nlm.nih.gov/pubmed/21572038", "http://www.ncbi.nlm.nih.gov/pubmed/9013954", "http://www.ncbi.nlm.nih.gov/pubmed/19453274", "http://www.ncbi.nlm.nih.gov/pubmed/9551364", "http://www.ncbi.nlm.nih.gov/pubmed/11231276", "http://www.ncbi.nlm.nih.gov/pubmed/18931123" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021382" ]

[ "FOXOs are reliable markers of longevity." ]

[ "yes" ]

[ "Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan.", "In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.", "Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. ", "Components of anti-ageing and autophagy include SirTs and FoxOs.", "Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.", "Forkhead box O (FOXO) transcription factors are involved in various cellular processes, including cell proliferation, stress resistance, metabolism, and longevity", "In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. ", "Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.", "Many longevity genes, e.g. FoxOs and SIRT1, are inhibitors of NF-kappaB signaling. ", "Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging process and extend lifespan.", "Yet, FoxOs also can significantly affect normal cell survival and longevity, requiring new treatments for neoplastic growth to modulate novel pathways that integrate cell proliferation, metabolism, inflammation and survival.", "These observations link FoxO function in mammalian systems with the evolutionarily conserved role of FoxO in promotion of stress resistance and longevity in lower phylogenetic systems. Furthermore, these findings have implications for aging in higher organisms and in malignant stem cell biology, and suggest that FoxOs may play an important role in the maintenance and integrity of stem cell compartments in a broad spectrum of tissues.", "Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing.", "This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.", "In this review, we focus on the several interactions of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-kappaB signaling pathways. We provide evidence that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-kappaB signaling and simultaneously protect against inflamm-aging process.", "In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. ", "In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases.", "FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20874444", "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "http://www.ncbi.nlm.nih.gov/pubmed/18208360", "http://www.ncbi.nlm.nih.gov/pubmed/21076489", "http://www.ncbi.nlm.nih.gov/pubmed/15942449", "http://www.ncbi.nlm.nih.gov/pubmed/20592766", "http://www.ncbi.nlm.nih.gov/pubmed/19408108", "http://www.ncbi.nlm.nih.gov/pubmed/21431325", "http://www.ncbi.nlm.nih.gov/pubmed/15126506", "http://www.ncbi.nlm.nih.gov/pubmed/19861158", "http://www.ncbi.nlm.nih.gov/pubmed/18371346", "http://www.ncbi.nlm.nih.gov/pubmed/21114762", "http://www.ncbi.nlm.nih.gov/pubmed/22187289", "http://www.ncbi.nlm.nih.gov/pubmed/19066462", "http://www.ncbi.nlm.nih.gov/pubmed/18193389" ]

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"s": "http://purl.uniprot.org/uniprot/B4G4S8", "o": "http://linkedlifedata.com/resource/#_42344734533800E" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344734533800E", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344734533800E", "o": "GL24235" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344734533800D", "o": "Forkhead box protein O" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "C477334" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1311653", "o": "http://linkedlifedata.com/resource/umls/label/A3832745" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "FOXO protein, Drosophila" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1311653", "o": "http://linkedlifedata.com/resource/umls/label/A3832745" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "MeSH" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B3LYS5", "o": "http://linkedlifedata.com/resource/#_42334C59533500D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42334C59533500C", "o": "Forkhead box protein O" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42334C59533500D", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42334C59533500D", "o": "GF16233" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4NFR1", "o": "http://linkedlifedata.com/resource/#_42344E46523100B" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344E46523100B", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344E46523100A", "o": "Forkhead box protein O" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344E46523100B", "o": "GK22687" } ]

[ "http://www.uniprot.org/uniprot/FOXO_DROME", "http://www.uniprot.org/uniprot/FOXO_DROSE", "http://www.uniprot.org/uniprot/FOXO_DROPE", "http://www.uniprot.org/uniprot/FOXO_DROMO", "http://www.uniprot.org/uniprot/FOXO_CAEEL", "http://www.uniprot.org/uniprot/FOXO_DROPS", "http://www.uniprot.org/uniprot/FOXO_DROGR", "http://www.uniprot.org/uniprot/FOXO_DROYA", "http://www.uniprot.org/uniprot/FOXO_DROWI", "http://www.uniprot.org/uniprot/FOXO_DROAN", "http://www.uniprot.org/uniprot/FOXO_DROVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008136", "http://www.uniprot.org/uniprot/FOXO_DROER" ]

[ "The syndrome defined by Bickerstaff of progressive, external ophthalmoplegia and ataxia, with disturbance of consciousness or hyperreflexia, has subsequently been associated with antiganglioside antibody, anti-GQ1b" ]

[ "antiganglioside antibody" ]

[ "In addition, BBE and Fisher syndrome, which are clinically similar and are both associated with the presence of the immunoglobulin G anti-GQ1b antibody, represent a specific autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia.", "The syndrome defined by Bickerstaff of progressive, external ophthalmoplegia and ataxia, with disturbance of consciousness or hyperreflexia, has subsequently been associated with anti-GQ1b antibodies.", "An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody.", "Serologic analysis of antibodies against ganglioside complexes (anti-GDIa, anti-GDIb, anti-GM1, anti-GM2, anti-GM3, anti-GQIb and anti-GTIb antibodies) showed negative results.", "However, contrary to a proposed anti-GQ1b antibody syndrome, we would suggest that pathogenesis of this clinical spectrum is not limited to anti-ganglioside antibodies.", "Although there are usually no abnormalities in MFS by routine neuroimaging, in a few cases, contrast enhancement of nerve roots and signs of central nervous system involvement were described supporting the hypothesis of an anti-GQ1b-syndrome, a continuum involving GBS, MFS, and Bickerstaff's brainstem encephalitis. ", "Anti-GM1 IgG, GD1a IgG, GQ1b IgG, and GT1a IgG antibodies were positive.", "The discovery of the association of the anti-GQ1b IgG antibody with the postinfectious clinical syndromes of ophthalmoplegia, ataxia, and areflexia helped house the phenotypes of the Miller Fisher syndrome (MFS), atypical MFS, Guillain-Barré syndrome with ophthalmoplegia, and Bickerstaff's brainstem encephalitis under one roof. ", "These findings suggest that host susceptibility may play a role in inducing the production of anti-ganglioside antibodies and the development of Bickerstaff's brainstem encephalitis.", "These antibodies should provide useful serological markers for identifying patients who have atypical GBS with preserved deep tendon reflexes, ataxic GBS, Bickerstaff's brainstem encephalitis or acute ophthalmoparesis, especially for those who have no antibodies to GM1, GD1a or GQ1b.", "Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome.", "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies.", "Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection.", "Bickerstaff's brainstem encephalitis, Miller Fisher syndrome and Guillain-Barré syndrome overlap in an asthma patient with negative anti-ganglioside antibodies.", "Bickerstaff brainstem encephalitis is a clinical syndrome of ophthalmoplegia, cerebellar ataxia, and central nervous system signs and is associated with the presence of anti-GQ1b antibodies.", "This is only the second case in the literature of Bickerstaff brainstem encephalitis with raised titers of anti-GQ1b antibodies described in association with M pneumoniae infection.", "Of those patients with Fisher syndrome, Bickerstaff's brainstem encephalitis, ataxic GBS or acute ophthalmoparesis, 33% of 67 anti-GM1b-positive, and 52% of 25 anti-GalNAc-GD1a-positive patients had no anti-GQ1b antibodies.", "Fisher syndrome or Bickerstaff brainstem encephalitis? Anti-GQ1b IgG antibody syndrome involving both the peripheral and central nervous systems.", "Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO).", "This case presented clinical characteristics of three syndromes concurrently-Fisher syndrome, Bickerstaff brainstem encephalitis, and Guillain-Barré syndrome-that may be collectively called 'anti-GQ1b IgG antibody syndrome'.", "This is the case of a 79-year-old man with chronic lymphocytic leukemia who presented with Guillain-Barré syndrome with features overlapping with the Miller Fisher syndrome and Bickerstaff brainstem encephalitis and positive antiganglioside GQ1b antibody about 6 months after treatment with bendamustine and rituximab.", "Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome", "[A case report of Bickerstaff's brainstem encephalitis with positive anti GQ 1 b, GT 1 a, GM 1 ganglioside antibodies].", "[Probable Bickerstaff's brainstem encephalitis associated with anti-GQ1b antibody].", "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies. ", "Nevertheless, 66% of patients with Bickerstaff syndrome have anti-GQ1b antibody during the acute phase period.", "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies.", "Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "http://www.ncbi.nlm.nih.gov/pubmed/11442445", "http://www.ncbi.nlm.nih.gov/pubmed/21631649", "http://www.ncbi.nlm.nih.gov/pubmed/25379047", "http://www.ncbi.nlm.nih.gov/pubmed/24853856", "http://www.ncbi.nlm.nih.gov/pubmed/16844234", "http://www.ncbi.nlm.nih.gov/pubmed/8194267", "http://www.ncbi.nlm.nih.gov/pubmed/18678825", "http://www.ncbi.nlm.nih.gov/pubmed/23275783", "http://www.ncbi.nlm.nih.gov/pubmed/22984203", "http://www.ncbi.nlm.nih.gov/pubmed/16948943", "http://www.ncbi.nlm.nih.gov/pubmed/16099076", "http://www.ncbi.nlm.nih.gov/pubmed/23927937", "http://www.ncbi.nlm.nih.gov/pubmed/11002482", "http://www.ncbi.nlm.nih.gov/pubmed/12451613", "http://www.ncbi.nlm.nih.gov/pubmed/18717185", "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "http://www.ncbi.nlm.nih.gov/pubmed/19664367" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004660", "http://www.disease-ontology.org/api/metadata/DOID:9588" ]

[ "Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients." ]

[ "miR-155", "miR-146a", "miR-124a", "miR-222", "miR-223", "miR-203", "miR-346", "miR-132", "miR-363", "miR-498", "miR-15a", "miR-16", "miR-18a" ]

[ "This study provides the first description of increased expression of miRNA miR-155 and miR-146a in RA", "In this study we investigated the expression, regulation, and function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue", "The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA)", "This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFalpha and IL-1beta", "pregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients", "Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR", "Rheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals", "Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-alpha production in patients with rheumatoid arthritis", "Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-alpha production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-alpha production", "icroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis", "We found that miR-124a levels significantly decreased in RA synoviocytes as compared with OA synoviocytes", "Induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins", "he results of this study suggest that miR-124a is a key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes", "iR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis.", "Although a multifactorial pathogenesis has been hypothesized, the precise mechanisms leading to the disease are still poorly understood at the molecular level. miRNA expression profile analysis highlighted that miR-223 is the only miRNA that is strikingly deregulated in peripheral T-lymphocytes from RA patients compared with healthy donors", "In summary, our data provide a first characterization of the miRNA expression profiles of peripheral T-lymphocytes of RA patients, identifying miR-223 as overexpressed in CD4(+) naive T-lymphocytes from these individuals", "Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis", "The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry", "We have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-alpha levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets", "icroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients", "Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells", "These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients", "polymorphism in the 3'-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility", "MicroRNA-146a was found to be increased in synovial fibroblasts, synovial tissue and PBMC from patients with RA", "This is the first study that addresses association of a variant in a target of miR-146a, IRAK1 gene, with RA susceptibility", "ltered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation", "Previously, we described increased expression of miR-155 and miR-146a in rheumatoid arthritis (RA) and showed a repressive effect of miR-155 on matrix metalloproteinase (MMP) expression in RA synovial fibroblasts (RASFs)", "The current results demonstrate methylation-dependent regulation of miR-203 expression in RASFs", " Importantly, they also show that elevated levels of miR-203 lead to increased secretion of MMP-1 and IL-6 via the NF-κB pathway and thereby contribute to the activated phenotype of synovial fibroblasts in RA", "iR-124a as a key regulator of proliferation and MCP-1 secretion in synoviocytes from patients with rheumatoid arthritis", "Transfection of miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G1 phase", "It is proposed that miR-124a is a key miRNA in the post-transcriptional regulatory mechanisms of RA synoviocytes, and has a therapeutic potential", "Expression of miR-146a and miR-16 in peripheral blood mononuclear cells of patients with rheumatoid arthritis and their correlation to the disease activity", "The elevated expression levels of miR-146a and miR-16 are correlated to RA disease activity, suggesting their value in assessment of the clinical disease activity of RA", "iR-346 controls release of TNF-α protein and stability of its mRNA in rheumatoid arthritis via tristetraprolin stabilization", "Using a microarray, we found two miRNAs, miR-125b and miR-939 predicted to target the 3'-UTR of TNF-α mRNA, to be up-regulated in RA FLS in response to LPS, but their repression did not restore mature TNF-α expression in FLS", "We showed previously that miR-346, which is upregulated in LPS-activated FLS, inhibited Btk expression that stabilized TNF-α mRNA", "Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients", "own-regulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts promotes apoptosis resistance", "Basal expression levels of miR-34a* were found to be reduced in synovial fibroblasts from RA patients compared to osteoarthritis patients, whereas levels of miR-34a, miR-34b/b*, and miR-34c/c* did not differ", "Our data provide evidence of a methylation-specific down-regulation of proapoptotic miR-34a* in RASFs", "dentification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model", "miR-seq demonstrated that TghuTNF-SF exhibit a distinct pathogenic profile with 22 significantly upregulated and 30 significantly downregulated miR", "Validation assays confirmed the dysregulation of miR-223, miR-146a and miR-155 previously associated with human rheumatoid arthritis (RA) pathology, as well as that of miR-221/222 and miR-323-3p", "the authors identified miR-221/222 and miR-323-3p as novel dysregulated miR in RA SF", "Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases", "iR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients.", "verexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation", "MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis", "MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro", "This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients", "MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium", "ssociation of pre-miRNA-146a rs2910164 and pre‑miRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis", "Our findings demonstrated that the hsa-mir-499 rs3746444, but not mir-146a rs2910164, polymorphism is associated with an increased RA risk in a sample of the Iranian population", "umor necrosis factor α-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-κB signaling", "To elucidate whether the microRNA (miRNA) cluster miR-17-92 contributes to the activated phenotype of rheumatoid arthritis synovial fibroblasts (RASFs", "We found that TNFα induces the expression of miR-17-92 in RASFs in an NF-κB-dependent manner", "Using reporter gene assays, we identified the NF-κB pathway inhibitor TNFα-induced protein 3 as a new target of miR-18a", "Our data suggest that the miR-17-92-derived miR-18a contributes to cartilage destruction and chronic inflammation in the joint through a positive feedback loop in NF-κB signaling, with concomitant up-regulation of matrix-degrading enzymes and mediators of inflammation in RASFs", "As inflammation and joint damage are the main hallmarks of RA, we focused on the three miRNAs, miR-146a, miR-155 and miR-223, whose functions have been studied in both the processes and the pathogenic role investigated in the experimental models", "Focusing on the role of miR-146a, miR-155 and miR-223 in RA pathogenesis emphasizes the intertwined relationships between bone homeostasis and immunity, and the prominent role of monocytes in RA", "In a final perspective section we discuss the potential impact of therapeutic miR-155 modulation in RA", "correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients", "We demonstrated a highly significant linear correlation between miR-146a and miR-155 expression in PBMC and whole blood, from both healthy individuals and RA patients.", "expression of specific microRNAs (miRNA) in peripheral blood-derived mononuclear cells (PBMC), particularly miR-146a and miR-155, is associated with rheumatoid arthritis (RA)", "icroRNA-323-3p with clinical potential in rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy", "It has been shown that miR-323-3p associates with the pathogenesis of several diseases, such as rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20840794", "http://www.ncbi.nlm.nih.gov/pubmed/18383392", "http://www.ncbi.nlm.nih.gov/pubmed/21611196", "http://www.ncbi.nlm.nih.gov/pubmed/23649045", "http://www.ncbi.nlm.nih.gov/pubmed/21600203", "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "http://www.ncbi.nlm.nih.gov/pubmed/22161761", "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "http://www.ncbi.nlm.nih.gov/pubmed/21339228", "http://www.ncbi.nlm.nih.gov/pubmed/22823586", "http://www.ncbi.nlm.nih.gov/pubmed/21339227", "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "http://www.ncbi.nlm.nih.gov/pubmed/20459811", "http://www.ncbi.nlm.nih.gov/pubmed/24283221", "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "http://www.ncbi.nlm.nih.gov/pubmed/19931339", "http://www.ncbi.nlm.nih.gov/pubmed/24120842", "http://www.ncbi.nlm.nih.gov/pubmed/23318734", "http://www.ncbi.nlm.nih.gov/pubmed/21416408", "http://www.ncbi.nlm.nih.gov/pubmed/18438844", "http://www.ncbi.nlm.nih.gov/pubmed/22100329", "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "http://www.ncbi.nlm.nih.gov/pubmed/23385088", "http://www.ncbi.nlm.nih.gov/pubmed/20223711", "http://www.ncbi.nlm.nih.gov/pubmed/20870441", "http://www.ncbi.nlm.nih.gov/pubmed/20864373", "http://www.ncbi.nlm.nih.gov/pubmed/21354921", "http://www.ncbi.nlm.nih.gov/pubmed/22494429", "http://www.ncbi.nlm.nih.gov/pubmed/23138379", "http://www.ncbi.nlm.nih.gov/pubmed/22562984" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009405" ]

[ "Yes, FGFR3 mutation is associated with plagiocephaly. It is the most common mutation in plagiocephaly. FGFR genes have important effects on bone development, and mutations in 4 \"hot spot\" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly." ]

[ "yes" ]

[ "Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly. The most common achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3 (FGFR3) gene, was detected. ", " The most common mutation for achondroplasia (FGFR3 Gly380Arg, resulting in 1138G>A) was identified. Imaging studies disclosed complex craniosynostosis and neurosurgical intervention was carried out, particularly for posterior plagiocephaly.", "FGFR mutations and plagiocephaly.", "FGFR genes have important effects on bone development, and mutations in 4 \"hot spot\" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly. ", "Mutation analyses in the FGFR3 gene revealed nucleotide alterations located in the mutational hot spot at amino acid residue 250 (g.C749).", "RESULTS: In our cohort of 159 patients with various craniosynostosis syndromes, mutations were found in 100% of patients with Apert syndrome, 83.3% with Pfeiffer syndrome, 72.7% with Crouzon syndrome, 50.0% with Saethre-Chotzen syndrome, 27.7% with plagiocephaly, 31.8% with brachicephaly, 20% of complex cases, and 6.9% of mixed cases. ", "The genetic alterations that could cause unilateral coronal synostosis are more elusive.", "Mutations were found in eight of 47 patients: two patients with different single-amino-acid changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with TWIST mutations. ", "Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. ", "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation.", "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly.", "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation.", "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation.", "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children&apos;s Hospital of Philadelphia were evaluated for the FGFR3 mutation", "FGFR genes have important effects on bone development, and mutations in 4 &quot;hot spot&quot; exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly", "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation", "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation", "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly", "FGFR mutations and plagiocephaly", "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation. ", "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. ", "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly. ", " To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and 33 were negative for this mutation.", "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation.", "In a girl with seemingly isolated plagiocephaly we identified a P250L (749C-->T) mutation in FGFR3.", "FGFR mutations and plagiocephaly.", "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation.", "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23949953", "http://www.ncbi.nlm.nih.gov/pubmed/21739570", "http://www.ncbi.nlm.nih.gov/pubmed/17693524", "http://www.ncbi.nlm.nih.gov/pubmed/17992550", "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "http://www.ncbi.nlm.nih.gov/pubmed/14577033", "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "http://www.ncbi.nlm.nih.gov/pubmed/15253176", "http://www.ncbi.nlm.nih.gov/pubmed/18216705" ]

[]

[ "http://www.uniprot.org/uniprot/FGFR3_CHICK", "http://www.uniprot.org/uniprot/FGFR3_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049068", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/FGFR3_PLEWA", "http://www.uniprot.org/uniprot/FGFR3_DANRE", "http://www.uniprot.org/uniprot/FGFR3_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059041" ]

[ "Yes, several isoforms (obtained by by usage of ten variant exons in various combinations) have been causally related to metastasis." ]

[ "yes" ]

[ "CD44 variants and prognosis", "The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas.", "Positive CD44v3 expression was associated with more advanced pathological stage and poorer prognosis than negative CD44v3 expression", "CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients", "D44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker", "CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas", "analysis of CD44v expression provides indications of biological and clinical relevance also in low grade lymphoproliferative disorders", "clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia", "CD44 variants and its association with survival in pancreatic cancer", "CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors", "CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer", "CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance.", "combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance", "variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas.", "expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer", "a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC", "Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs", "different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis", "D44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer", "Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma", "Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis", "In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7587629", "http://www.ncbi.nlm.nih.gov/pubmed/9732216", "http://www.ncbi.nlm.nih.gov/pubmed/10601048", "http://www.ncbi.nlm.nih.gov/pubmed/12842543", "http://www.ncbi.nlm.nih.gov/pubmed/9849582", "http://www.ncbi.nlm.nih.gov/pubmed/7585612", "http://www.ncbi.nlm.nih.gov/pubmed/7544777", "http://www.ncbi.nlm.nih.gov/pubmed/9742519", "http://www.ncbi.nlm.nih.gov/pubmed/11751503", "http://www.ncbi.nlm.nih.gov/pubmed/9949626", "http://www.ncbi.nlm.nih.gov/pubmed/9815811", "http://www.ncbi.nlm.nih.gov/pubmed/8869105", "http://www.ncbi.nlm.nih.gov/pubmed/9224749", "http://www.ncbi.nlm.nih.gov/pubmed/12747468", "http://www.ncbi.nlm.nih.gov/pubmed/9413216" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009362", "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=D018960", "http://www.uniprot.org/uniprot/CD44_BOVIN" ]

[ "Yes. Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy. Quoted results vary from 26 to 90% . Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency." ]

[ "yes" ]

[ "Mindfulness-based stress reduction appears to be a treatment worthy of further study, as in the short term, it is as effective as historical studies of drug treatment and bladder training in reducing urge incontinence and incontinence-related quality of life.", "All patients, irrespective of the results of cystometry were subsequently treated with oxybutynin 2.5 mg twice daily along with bladder training.", "Of the 29 patients with stable bladder and symptoms of OAB, 100% cure rate was achieved in 20 (68.9%) and 06 (20.6%) patients respectively. While in 3 patients in both groups, decrease of symptoms upto 75% after 6 months of treatment was observed.", "Both urodynamically proven unstable and stable bladder showed nearly equal improvement with treatment", "There are 3 types of urine incontinence (urge-, stress-, and overflow-incontinence). Another standardization of urinary incontinence follows dysfunctions of the pelvic floor: detrusor muscle-dependent, due to sphincter spasm, prostate gland dependent. Urge incontinence with a dysfunction of the detrusor muscle is the most common type. Mixed types are frequent. Non-drug measures (e.g. pelvic muscle training, bladder training, toilet training are first choice treatments.", "Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered.", "Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional voiding were evaluated. After a no-treatment control period (average 6 months), patients underwent a 6-day bladder training course", "Six months after training completion, 64.1% and 64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and 17.7% of the inpatient and outpatient groups with nighttime wetting were cured or had improved", "Of the inpatient group with urge incontinence, the functional bladder capacity increased by 15%.", "To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder.", "CONCLUSIONS: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.", "Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women.", "OBJECTIVE: To evaluate the long-term effect of treatment of female incontinence by the general practitioner (pelvic floor exercises, and bladder training) in female urinary incontinence.", "Stress incontinence and urge incontinence were treated by means of pelvic floor exercises and bladder training respectively, while a mixed incontinence was treated by bladder training followed by pelvic floor exercises. T", "The treatment consisted of training of pelvic muscles in stress incontinence and bladder training in urge incontinence", "RESULTS: After 3 months the mean frequency of urine loss per week diminished from 21 to 8, and after 12 months to 6 times.", "Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice", "for eight out of nine women their continence had improved, both subjectively and objectively.", "Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy", "Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence.", "After 3 months about 60% of the patients were either dry or only mildly incontinent", "terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence", "Basing on our experience with 39 patients with severe urge incontinence (in one-quarter of the cases pure urge incontinence, in one-half of the cases mixed incontinence and in a further quarter of the cases neurogenic bladder disorders) a supervised programme (mictiogram) and a well-tried therapy (especially in the Anglo-Saxon countries) consisting of the triad hospitalisation/bladder training/medication therapy are presented. After an average hospitalisation period of 14 days, we were able to achieve a symptom-free state in 94% of the patients.", "Anamnestic and urodynamical results are evaluated before and after bladder retraining drill (BRD) in women suffering from urge incontinence.", "We could state that the BRD is a good possibility to realize multistep-therapy of female incontinence.", "Twenty consecutive female patients with urge incontinence and stable detrusor function on provocative rapid fill CO2-cystometry were treated as out-patients with a bladder training programme and with terodiline/placebo in a double-blind cross-over design.", "In conclusion, female patients with idiopathic urge incontinence and stable detrusor function did respond to treatment as do female patients with urge incontinence and proven instability.", "The results of in-patient bladder training in 65 women with frequency, urgency and urge incontinence are reported. There was a good initial response in 88%. By 6 months the response rate had fallen to 38%.", "Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency.", "Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2653554", "http://www.ncbi.nlm.nih.gov/pubmed/8006342", "http://www.ncbi.nlm.nih.gov/pubmed/3704568", "http://www.ncbi.nlm.nih.gov/pubmed/8185987", "http://www.ncbi.nlm.nih.gov/pubmed/12614251", "http://www.ncbi.nlm.nih.gov/pubmed/19174937", "http://www.ncbi.nlm.nih.gov/pubmed/10198479", "http://www.ncbi.nlm.nih.gov/pubmed/1459383", "http://www.ncbi.nlm.nih.gov/pubmed/8022508", "http://www.ncbi.nlm.nih.gov/pubmed/6887404", "http://www.ncbi.nlm.nih.gov/pubmed/22453268", "http://www.ncbi.nlm.nih.gov/pubmed/6534448", "http://www.ncbi.nlm.nih.gov/pubmed/3758628", "http://www.ncbi.nlm.nih.gov/pubmed/19281722", "http://www.ncbi.nlm.nih.gov/pubmed/8394146", "http://www.ncbi.nlm.nih.gov/pubmed/3765943", "http://www.ncbi.nlm.nih.gov/pubmed/20527606", "http://www.ncbi.nlm.nih.gov/pubmed/20877608", "http://www.ncbi.nlm.nih.gov/pubmed/12493360", "http://www.ncbi.nlm.nih.gov/pubmed/16413359" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053202", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001745", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001743", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549" ]

[ "Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals. OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible." ]

[]

[ "Online Mendelian Inheritance in Animals (OMIA),", "Online Mendelian Inheritance in Animals (OMIA)", "nline Mendelian Inheritance in Animals (OMIA) ", "Online Mendelian Inheritance in Animals (OMIA)", "Online Mendelian Inheritance in Animals (OMIA)", "Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals other than humans and mice", "Structured as a comparative biology resource, OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16381939", "http://www.ncbi.nlm.nih.gov/pubmed/21737319", "http://www.ncbi.nlm.nih.gov/pubmed/22140104", "http://www.ncbi.nlm.nih.gov/pubmed/18940862", "http://www.ncbi.nlm.nih.gov/pubmed/21982513", "http://www.ncbi.nlm.nih.gov/pubmed/17170002", "http://www.ncbi.nlm.nih.gov/pubmed/21097890" ]

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

[ "The first-line standard therapy for uveitis is topical and systemic corticosteroids, often reinforced by methotrexate as a second-line disease-modifying antirheumatic drug (DMARD). MTX has a topical steroid sparing effect as well. Early treatment with MTX is advocated to prevent complications such as cataract. There are no trial data on the effect of MTX. Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study). Biologic DMARDs can be used with Methotrexate in refractory uveitis as well." ]

[]

[ "To characterize disease-modifying antirheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and to determine patient factors associated with medication use.", "Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2, 95% CI 3.6-7.6), anticitrullinated protein antibodies (OR 4.5, 95% CI 1.7-12), and extended oligoarthritis (OR 4.1, 95% CI 2.5-6.6)", "About three-quarters of all children with JIA in the CARRA Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and their use was strongly associated with RF-positive polyarthritis, PsA, uveitis, and systemic arthritis.", "pediatric JIA patients who were being treated with MTX for active uveitis", "Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months", "Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study)", "The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.", "The risk factor for development of early cataract requiring surgery in children with JIA-associated uveitis is the presence of posterior synechia at the time of diagnosis of uveitis. However, early treatment with MTX is associated with a mean delay in the development of cataract requiring surgery of 3.5 years.", "MTX seems to be an effective therapy for JIA associated uveitis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17706583", "http://www.ncbi.nlm.nih.gov/pubmed/19707402", "http://www.ncbi.nlm.nih.gov/pubmed/17932849", "http://www.ncbi.nlm.nih.gov/pubmed/22034564", "http://www.ncbi.nlm.nih.gov/pubmed/15693100", "http://www.ncbi.nlm.nih.gov/pubmed/22859354", "http://www.ncbi.nlm.nih.gov/pubmed/21145533", "http://www.ncbi.nlm.nih.gov/pubmed/18949668" ]

[]

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[ "The 7-methylguanosine cap added to the 5′ end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. In the addition of 7-methylguanosine in mRNA involved the RNA polymerase II, RNA guanylyltransferase and RNA guanine-7 methyltransferase enzymes.", "The enzymes involved in the addition of 7-methylguanosine in mRNA are RNA guanylyltransferase and 5'-phosphatase (RNGTT), RNA guanine-7 methyltransferase (RNMT or hMTr1), RNMT-activating mini-protein (RAM), RNA polymerase II, S-adenosylhomocysteine hydrolase (SAHH), and Myc." ]

[ "RNA guanylyltransferase and 5'-phosphatase (RNGTT)", "RNA guanylyltransferase and 5'-phosphatase", "RNGTT", "RNA guanine-7 methyltransferase", "RNA guanine-7 methyltransferase (RNMT or hMTr1)", "RNMT", "hMTr1", "RNMT-activating mini-protein", "RNMT-activating mini-protein (RAM)", "RAM", "RNA polymerase II", "S-adenosylhomocysteine hydrolase", "S-adenosylhomocysteine hydrolase (SAHH)", "SAHH", "Myc" ]

[ "In mammals, cap synthesis is catalysed by the sequential action of RNGTT (RNA guanylyltransferase and 5'-phosphatase) and RNMT (RNA guanine-7 methyltransferase), enzymes recruited to RNA pol II (polymerase II) during the early stages of transcription. We recently discovered that the mammalian cap methyltransferase is a heterodimer consisting of RNMT and the RNMT-activating subunit RAM (RNMT-activating mini-protein). RAM activates and stabilizes RNMT and thus is critical for cellular cap methylation and cell viability.", "Synthesis of the methyl cap initiates with the addition of 7-methylguanosine to the initiating nucleotide of RNA pol II (polymerase II) transcripts, which occurs predominantly during transcription and in mammals is catalysed by RNGTT (RNA guanylyltransferase and 5' phosphatase) and RNMT (RNA guanine-7 methyltransferase).", "The RNMT-activating subunit, RAM (RNMT-activating miniprotein), is also recruited to transcription initiation sites via an interaction with RNMT.", "Phosphorylation of the CTD recruits RNGTT and RNMT, the enzymes involved in mRNA capping, to the nascent transcript.", "Myc induces methyl cap formation by promoting RNA polymerase II phosphorylation which recruits the capping enzymes to RNA, and by up-regulating the enzyme SAHH (S-adenosylhomocysteine hydrolase), which neutralizes the inhibitory by-product of methylation reactions.", "In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95).", "The guanylyltransferase (GTP:mRNA guanylyltransferase, EC 2.7.7.50) reaction responsible for cap formation usually proceeds via a covalent enzyme-GMP intermediate.", "The methylation of the 5' terminal guanosine residue of the cap structure of Semliki Forest virus (SFV) mRNAs has been shown to occur in vitro concomitantly with their synthesis (R. K. Cross and P. J. Gomatos, Virology, 114, 542-554, 1981). The enzyme responsible for this methylation, a guanine-7-methyltransferase, is associated with the SFV replication complex", "An RNA (guanine-7-)-methyltransferase that specifically methylates the 5'-terminal guanosine residue of RNAs ending in the dinucleoside triphosphate G(5')pppN- has been purified from the cytoplasm of HeLa cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20713356", "http://www.ncbi.nlm.nih.gov/pubmed/7831320", "http://www.ncbi.nlm.nih.gov/pubmed/24552703", "http://www.ncbi.nlm.nih.gov/pubmed/21170289", "http://www.ncbi.nlm.nih.gov/pubmed/23863084", "http://www.ncbi.nlm.nih.gov/pubmed/956186", "http://www.ncbi.nlm.nih.gov/pubmed/24273643", "http://www.ncbi.nlm.nih.gov/pubmed/6478055", "http://www.ncbi.nlm.nih.gov/pubmed/729595", "http://www.ncbi.nlm.nih.gov/pubmed/11879179", "http://www.ncbi.nlm.nih.gov/pubmed/21118133", "http://www.ncbi.nlm.nih.gov/pubmed/9707557", "http://www.ncbi.nlm.nih.gov/pubmed/2072458", "http://www.ncbi.nlm.nih.gov/pubmed/22817748", "http://www.ncbi.nlm.nih.gov/pubmed/9725672", "http://www.ncbi.nlm.nih.gov/pubmed/1002690", "http://www.ncbi.nlm.nih.gov/pubmed/6649413", "http://www.ncbi.nlm.nih.gov/pubmed/24200467", "http://www.ncbi.nlm.nih.gov/pubmed/22985415", "http://www.ncbi.nlm.nih.gov/pubmed/10662770" ]

[]

[ "http://www.uniprot.org/uniprot/MCE1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009452", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008618", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006370", "http://www.biosemantics.org/jochem#4270220", "http://www.uniprot.org/uniprot/RSMG_OENOB", "http://www.uniprot.org/uniprot/MCE1_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004484", "http://www.biosemantics.org/jochem#4270249", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.uniprot.org/uniprot/MCE_ASFP4", "http://www.uniprot.org/uniprot/MCE1_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020536", "http://www.biosemantics.org/jochem#4211619", "http://www.uniprot.org/uniprot/MCE_ASFB7", "http://www.biosemantics.org/jochem#4270250", "http://www.uniprot.org/uniprot/MCE_PBCV1", "http://www.uniprot.org/uniprot/MCE1_HUMAN", "http://www.biosemantics.org/jochem#4269944", "http://www.uniprot.org/uniprot/MCE_ASFK5", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046118", "http://www.uniprot.org/uniprot/MCE_ASFM2", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000340", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004789", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045762", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031533", "http://www.biosemantics.org/jochem#4195237", "http://www.uniprot.org/uniprot/MCE_MIMIV" ]

[ "HOCOMOCO is a comprehensive collection of human transcription factor binding sites models constructed by integration of binding sequences obtained by both low- and high-throughput methods. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source." ]

[]

[ "HOCOMOCO: a comprehensive collection of human transcription factor binding sites models.", "We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. We selected only one TFBS model per TF, unless there was a clear experimental evidence for two rather distinct TFBS models. We assigned a quality rating to each model. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source.", "We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods", "HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source", "HOCOMOCO: a comprehensive collection of human transcription factor binding sites models", "We show that integration of TFBS data from various types of experiments into a single model typically results in the improved model quality probably due to partial correction of source specific technique bias. We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23175603" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157" ]

[ "Psoriasin (S100A7) was originally identified in psoriasis." ]

[ "psoriasis" ]

[ "Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family", "Psoriasin (S100 A7) was discovered two decades ago as a protein abundantly expressed in psoriatic keratinocytes. ", " Psoriasin, originally isolated from psoriasis as an overexpressed molecule of unknown function, has recently been identified as a principal Escherichia coli-killing antimicrobial peptide of healthy skin. ", "Inflammation-prone psoriatic skin constitutively expresses elevated concentrations of S100A7 (psoriasin)", "S100A7 (psoriasin) and S100A15 (koebnerisin) were first identified in inflamed psoriatic skin. ", "Human psoriasin (S100A7) has originally been described as a member of the family of S100 calcium-binding proteins which is overexpressed in patients suffering from psoriasis. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22189627", "http://www.ncbi.nlm.nih.gov/pubmed/21148126", "http://www.ncbi.nlm.nih.gov/pubmed/21501383", "http://www.ncbi.nlm.nih.gov/pubmed/21551409", "http://www.ncbi.nlm.nih.gov/pubmed/19167844", "http://www.ncbi.nlm.nih.gov/pubmed/20596736" ]

[]

[]

[ "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption.\nPatients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose." ]

[ "yes" ]

[ "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption", "Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine.", "Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment.", "PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT4 replacement. Patients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15073769", "http://www.ncbi.nlm.nih.gov/pubmed/16477543", "http://www.ncbi.nlm.nih.gov/pubmed/22019751", "http://www.ncbi.nlm.nih.gov/pubmed/7865648", "http://www.ncbi.nlm.nih.gov/pubmed/16971728", "http://www.ncbi.nlm.nih.gov/pubmed/18942671", "http://www.ncbi.nlm.nih.gov/pubmed/18996189", "http://www.ncbi.nlm.nih.gov/pubmed/20694403", "http://www.ncbi.nlm.nih.gov/pubmed/16918738", "http://www.ncbi.nlm.nih.gov/pubmed/19942153", "http://www.ncbi.nlm.nih.gov/pubmed/17669709", "http://www.ncbi.nlm.nih.gov/pubmed/9416973", "http://www.ncbi.nlm.nih.gov/pubmed/23565522" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6850734", "o": "Proton Pump Inhibitors" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017494", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054328" ]

[ "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.Per3, a circadian gene, is required for Chk2 activation in human cells.", "Per3, a circadian gene, is required for Chk2 activation in human cells. ", "Per3, a circadian gene, is required for Chk2 activation in human cells.Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,", "Per3 gene, involved in circadian rhythm control, is required for Chk2 activation in human cells." ]

[ "yes" ]

[ "Per3, a circadian gene, is required for Chk2 activation in human cells.", "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.", "Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,", "Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death.", "These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis.", "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells", "Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM", "In addition, Per3 physically interacted with ATM and Chk2" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21070773" ]

[]

[ "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://www.uniprot.org/uniprot/PER3_HUMAN" ]

[ "Low T3 Syndrome is the more frequent alteration of thyroid hormone profile early after coronary artery bypass graft surgery." ]

[ "Low T3 syndrome occurs frequently after CABG" ]

[ "FT3 concentration dropped significantly (p < 0.0001), reaching its lowest value 12 hours postoperatively. There were no significant differences between CPB and OPCAB patients. ", "In on-pump CABG surgery, inflammatory effects encompass activation of total leukocytes, neutrophils and platelets, reduction of serum level of total proteins and albumin and decreased thyroid hormones levels, especially within first postoperative 24 hours.", "Typical NTIS was observed in all patients, and the FT3 concentration was still reduced by postoperative day 5 (p<0.0001).", "We could demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those patients with low T3 concentrations prior to surgery demonstrate postoperatively a more severe degree of nonthyroidal illness (NTI).", "It is concluded that the coronary bypass operation evokes a rapid decline in T3, which is not normalized by the TSH induced response of the thyroid gland, while the post-operative period is characterized by a \"low T3 state\". " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/6422832", "http://www.ncbi.nlm.nih.gov/pubmed/15843233", "http://www.ncbi.nlm.nih.gov/pubmed/22358266", "http://www.ncbi.nlm.nih.gov/pubmed/12537197", "http://www.ncbi.nlm.nih.gov/pubmed/9010711" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "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=D001026", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327", "http://www.disease-ontology.org/api/metadata/DOID:3393" ]

[ "A number of proteins have been found to regulate F-actin bundling and enhance filopodia formation and motility. Among these are Cysteine-rich protein 1 (CRP1), Fascin, Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2), Insulin receptor tyrosine kinase substrate p53 (IRSp53), Missing in metastasis protein (MIM), Eps8, Diaphanous-related formin (dDia2) and Vasodilator-stimulated phosphoprotein (VASP)." ]

[ "Cysteine-rich protein 1 (CRP1)", "Fascin", "Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2)", "Insulin receptor tyrosine kinase substrate p53 (IRSp53)", "Missing in metastasis protein (MIM)", "Eps8", "Diaphanous-related formin (dDia2)", "Vasodilator-stimulated phosphoprotein (VASP)" ]

[ "CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth", "CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells.", "Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons.", "Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons.", "Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity.", "F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.", "In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression.", "In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties.", "Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia.", "The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages", "Overexpression of MAYP decreased CSF-1-induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis.", "The opposite phenotype was observed with reduced expression of MAYP, indicating that MAYP is a negative regulator of CSF-1-induced membrane ruffling and positively regulates formation of filopodia and directional migration.", "Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro.", "In addition, MAYP colocalized with cortical and filopodial F-actin in vivo.", "Because filopodia are postulated to increase directional motility by acting as environmental sensors, the MAYP-stimulated increase in directional movement may be at least partly explained by enhancement of filopodia formation.", "We report an unexpected direct association between fascin, an actin-bundling component of filopodia, microspikes and lamellipodial ribs, and protein kinase Calpha (PKCalpha), a regulator of focal adhesions.", "Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.", "Actin-crosslinking proteins organize actin into highly dynamic and architecturally diverse subcellular scaffolds that orchestrate a variety of mechanical processes, including lamellipodial and filopodial protrusions in motile cells.", "IRSp53, a multi-domain protein that can associate with the Rho-GTPases Rac and Cdc42, participates in these processes mainly through its amino-terminal IMD (IRSp53 and MIM domain). The isolated IMD has actin-bundling activity in vitro and is sufficient to induce filopodia in vivo.", "Eps8 activates and synergizes with IRSp53 in mediating actin bundling in vitro, enhancing IRSp53-dependent membrane extensions in vivo.", "Consistently, Cdc42-induced filopodia are inhibited following individual removal of either IRSp53 or Eps8.", "Collectively, these results support a model whereby the synergic bundling activity of the IRSp53-Eps8 complex, regulated by Cdc42, contributes to the generation of actin bundles, thus promoting filopodial protrusions.", "The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation", "Filopodia are highly dynamic finger-like cell protrusions filled with parallel bundles of actin filaments. Previously we have shown that Diaphanous-related formin dDia2 is involved in the formation of filopodia. Another key player for the formation of filopodia across many species is vasodilator-stimulated phosphoprotein (VASP).", "It has been proposed that the essential role of VASP for formation of filopodia is its competition with capping proteins for filament barbed-end interaction.", "Only WT DdVASP, but not a mutant lacking the F-actin bundling activity, could rescue the ability of these cells to form WT-like filopodia.", "Our data suggest that DdVASP is complexed with dDia2 in filopodial tips and support formin-mediated filament elongation by bundling nascent actin filaments.", "Insulin receptor tyrosine kinase substrate p53 (IRSp53) has been identified as an SH3 domain-containing adaptor that links Rac1 with a Wiskott-Aldrich syndrome family verprolin-homologous protein 2 (WAVE2) to induce lamellipodia or Cdc42 with Mena to induce filopodia.", "Here, we show that the N-terminal predicted helical stretch of 250 amino acids of IRSp53 is an evolutionarily conserved F-actin bundling domain involved in filopodium formation.", "The IMD alone, derived from either IRSp53 or MIM, induced filopodia in HeLa cells and the formation of tightly packed parallel F-actin bundles in vitro.", "These results suggest that IRSp53 and MIM belong to a novel actin bundling protein family.", "Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia", "Fascin localized to radially oriented actin bundles in lamellipodia (ribs) and filopodia.", "Using a fascin antibody and a GFP fascin construct, we found that fascin incorporated into actin bundles from the beginning of growth cone formation at the cut end of axons.", "Later, during growth cone morphogenesis when actin ribs shortened, the proximal fascin-free zone of bundles increased, but fascin was retained in the distal, filopodial portion of bundles.", "Treatment with tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which phosphorylates fascin and decreases its affinity for actin, resulted in loss of all actin bundles from growth cones.", "Our findings suggest that fascin may be particularly important for the linear structure and dynamics of filopodia and for lamellipodial rib dynamics by regulating filament organization in bundles." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "http://www.ncbi.nlm.nih.gov/pubmed/21283078", "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "http://www.ncbi.nlm.nih.gov/pubmed/19228738", "http://www.ncbi.nlm.nih.gov/pubmed/18835624", "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "http://www.ncbi.nlm.nih.gov/pubmed/14532112", "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "http://www.ncbi.nlm.nih.gov/pubmed/20137952" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011554", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051490", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032432", "http://www.uniprot.org/uniprot/FSCN1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051764", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051491", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051489", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008840", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046847", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000199", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032233", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032232", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032231", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051017", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070650" ]

[ "SAGA stands for Spt-Ada-Gcn5-acetyltransferase (SAGA)" ]

[ "Spt-Ada-Gcn5-acetyltransferase" ]

[ "SAGA (Spt-Ada-Gcn5 Acetyltransferase)", "SAGA (Spt-Ada-Gcn5-acetyltransferase)", "Spt-Ada-Gcn5-acetyltransferase (SAGA) ", "Spt-Ada-Gcn5-acetyltransferase (SAGA) complex is a transcription coactivator ", "the yeast transcriptional coactivator Spt-Ada-Gcn5 acetyltransferase (SAGA)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25015293", "http://www.ncbi.nlm.nih.gov/pubmed/25441028", "http://www.ncbi.nlm.nih.gov/pubmed/26100014", "http://www.ncbi.nlm.nih.gov/pubmed/24509845", "http://www.ncbi.nlm.nih.gov/pubmed/26528322" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "C507785" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1700223", "o": "http://linkedlifedata.com/resource/umls/label/A10002967" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "SAGA complex, S cerevisiae" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1700223", "o": "http://linkedlifedata.com/resource/umls/label/A10002967" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "SAGA family complex" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "SAGA-type complex" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "Spt-Ada-Gcn5-acetyltransferase complex" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "SAGA complex" } ]

[ "http://www.uniprot.org/uniprot/SGF29_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000124", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036285", "http://www.uniprot.org/uniprot/SGF73_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043234" ]

[ "Phosphorylated TSC1 (hamartin) interacts with Plk1 independent of TSC2 (tuberin), with all three proteins present in a complex, and negatively regulates the protein levels of Plk1, to control centrosome duplication." ]

[]

[ "Phosphorylated hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex.", "Hamartin negatively regulates the protein levels of Plk1.", "Finally, Tsc1(-/-) mouse embryonic fibroblasts (MEFs) have increased number of centrosomes and increased DNA content, compared to Tsc1(+/+) cells.", "Both phenotypes are rescued after pre-treatment with the mTOR inhibitor rapamycin. RNAi inhibition of Plk1 in Tsc1(-/-) MEFs failed to rescue the increased centrosome number phenotype. These data reveal a novel subcellular localization for hamartin and a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR in the regulation of centrosome duplication." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16339216" ]

[]

[ "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.uniprot.org/uniprot/PLK1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596" ]

[ "The UPS2 proteomic dynamic range standard was introduced by the Association of Biomolecular Resource Facilities Proteomics Standards Research Group in 2006 and it has a dynamic range of 5 orders of magnitude." ]

[]

[ "the UPS2 proteomic dynamic range standard introduced by The Association of Biomolecular Resource Facilities Proteomics Standards Research Group in 2006)", "Universal Proteomics Standard sample with a dynamic range of 5 orders of magnitude (UPS2)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20823122", "http://www.ncbi.nlm.nih.gov/pubmed/24195105" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012015" ]

[ "Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein." ]

[ "Ataxin 2" ]

[ "Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein.", "In SCA2 brains, we found cytoplasmic, but not nuclear, microaggregates. Mice expressing ataxin-2 with Q58 showed progressive functional deficits accompanied by loss of the Purkinje cell dendritic arbor and finally loss of Purkinje cells.", "Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease caused by an expansion of polyglutamine tracts in the cytosolic protein ataxin-2 (Atx2). ", "Our analysis provides valuable information on the evolution and domain structure of Ataxin-2 proteins. Proline-rich motifs that may mediate protein interactions are widespread in Ataxin-2 proteins, but expansion of polyglutamine tracts associated with spinocerebellar ataxia type 2, is present only in primates, as well as some insects.", "The expansion of a polyQ repeat within the ataxin-2 protein causes spinocerebellar ataxia type 2 (SCA2). However, neither the precise pathological mechanism nor the physiological functions of ataxin-2 are known." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25027299", "http://www.ncbi.nlm.nih.gov/pubmed/19625506", "http://www.ncbi.nlm.nih.gov/pubmed/10973246", "http://www.ncbi.nlm.nih.gov/pubmed/24486837" ]

[]

[]

[ "Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids. Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein.", "Since the discovery of non-coding, small, highly structured, satellite RNAs (satRNAs) and viroids as subviral pathogens of plants , have been of great interest to molecular biologists as possible living fossils of pre-cellular evolution in an RNA world." ]

[ "Viroids" ]

[ "Since the discovery of non-coding, small, highly structured, satellite RNAs (satRNAs) and viroids as subviral pathogens of plants , have been of great interest to molecular biologists as possible living fossils of pre-cellular evolution in an RNA world.", "PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively.", "We show that viroids from the two known families are readily identified and their full-length sequences assembled by PFOR from small RNAs sequenced from infected plants. ", "Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein. ", "Viroids are small, circular, single-stranded RNA molecules that cause several infectious plant diseases. ", "Viroids: petite RNA pathogens with distinguished talents.", "Subviral pathogens of plants: viroids and viroidlike satellite RNAs.", "Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids.", "Subviral pathogens of plants: the viroids", "Viroids, satellite RNAs, satellites viruses and the human hepatitis delta virus form the 'brotherhood' of the smallest known infectious RNA agents, known as the subviral RNAs.", "Subviral pathogens of plants: the viroids.", "Viroids, subviral pathogens of plants, are composed of a single-stranded circular RNA of 246-399 nucleotides.", "During 1970 and 1971, I discovered that a devastating disease of potato plants is not caused by a virus, as had been assumed, but by a new type of subviral pathogen, the viroid. Viroids are so small--one fiftieth of the size of the smallest viruses--that many scientists initially doubted their existence. ", "The database of the smallest known auto-replicable RNA species: viroids and viroid-like RNAs.", "Viroids, satellite RNAs, satellites viruses and the human hepatitis delta virus form the &apos;brotherhood&apos; of the smallest known infectious RNA agents, known as the subviral RNAs.", " Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10494833", "http://www.ncbi.nlm.nih.gov/pubmed/10592219", "http://www.ncbi.nlm.nih.gov/pubmed/25503469", "http://www.ncbi.nlm.nih.gov/pubmed/16519798", "http://www.ncbi.nlm.nih.gov/pubmed/25731957", "http://www.ncbi.nlm.nih.gov/pubmed/15231279", "http://www.ncbi.nlm.nih.gov/pubmed/22345560", "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "http://www.ncbi.nlm.nih.gov/pubmed/16679345", "http://www.ncbi.nlm.nih.gov/pubmed/2672273", "http://www.ncbi.nlm.nih.gov/pubmed/15040183" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010944" ]

[ "Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection." ]

[ "Schistosoma spp" ]

[ "The laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers is difficult because the number of excreted eggs is often very limited.", "Eosinophilia (sometimes exceeding 50%) is often present in patients with acute schistosomiasis (Katayama fever), but may be limited or absent in late fibrotic manifestations of the disease.", "Laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers", "The specific diagnosis of early schistosomiasis and Katayama fever relies essentially on serologic tests or preferably on PCR (if available). ", "BACKGROUND: Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection.", "Schistosomiasis is a helminthic infection that is endemic in tropical and subtropical regions.", "In Africa, it predominantly manifests as urogenital disease, and the main infective agent is Schistosoma hematobium.", "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "OBJECTIVES: To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment.", "RESULTS: Twenty-three patients were diagnosed with Katayama fever by Schistosoma egg detection and/or by seroconversion. ", "The best therapeutic approach to acute schistosomiasis (Katayama fever) is still unsettled.", "Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp.", "Acute schistosomiasis, called safari's fever in Africa and Katayama fever in Japan, is an immunoallergic reaction due to transcutaneous penetration of infective cercaria.", "[Acute schistosomiasis (Katayama fever)].", "Acute schistosomiasis (Katayama fever): corticosteroid as adjunct therapy.", "Katayama fever or acute schistosomiasis probably occurs more commonly than is recorded.", "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "Three distinct syndromes caused by schistosomiasis have been described: cercarial dermatitis or swimmer's itch, acute schistosomiasis or Katayama fever, and chronic schistosomiasis.", "Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis.", "Early detection of circulating anodic antigen (CAA) in a case of acute schistosomiasis mansoni with Katayama fever.", " A 35-year-old man presented with fever and severe urticaria after visiting Uganda. His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever. .", "Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis.", "Three distinct syndromes caused by schistosomiasis have been described: cercarial dermatitis or swimmer&apos;s itch, acute schistosomiasis or Katayama fever, and chronic schistosomiasis.", " To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment. Between April 2000 and September 2004, we included prospectively all patients with confirmed diagnosis of Katayama fever.", "A 35-year-old man presented with fever and severe urticaria after visiting Uganda. His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment. Between April 2000 and September 2004, we included prospectively all patients with confirmed diagnosis of Katayama fever." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24985919", "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "http://www.ncbi.nlm.nih.gov/pubmed/8115806", "http://www.ncbi.nlm.nih.gov/pubmed/1411323", "http://www.ncbi.nlm.nih.gov/pubmed/2511623", "http://www.ncbi.nlm.nih.gov/pubmed/15582175", "http://www.ncbi.nlm.nih.gov/pubmed/24469437", "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "http://www.ncbi.nlm.nih.gov/pubmed/2515622", "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "http://www.ncbi.nlm.nih.gov/pubmed/24176480", "http://www.ncbi.nlm.nih.gov/pubmed/1901428", "http://www.ncbi.nlm.nih.gov/pubmed/22470757", "http://www.ncbi.nlm.nih.gov/pubmed/7676521", "http://www.ncbi.nlm.nih.gov/pubmed/10996126" ]

[]

[]

[ "Several clinical trials with androgen replacement therapy. \nStudy was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis. This trial was registered at clinical trials.gov as NCT00794079" ]

[ "androgen replacement trials", "omega-3 fatty acid supplementation", "NCT00794079" ]

[ "several clinical trials with androgen replacement therapy have failed to show clinical benefit.", "Clinical trials are needed to find better interventions for this syndrome.", "emergence of many promising interventions towards this age-related condition (e.g., physical exercise [in particular, resistance training], testosterone, antioxidant supplementations), the need for Phase II trial designs is high. ", "The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults.", "This trial was registered at clinical trials.gov as NCT00794079.", "The extreme paucity of clinical trials on sarcopenia in literature is mainly due to difficulties in designing studies able to isolate the aging process from its multiple and interconnected consequences." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21968872", "http://www.ncbi.nlm.nih.gov/pubmed/18615229", "http://www.ncbi.nlm.nih.gov/pubmed/22739566", "http://www.ncbi.nlm.nih.gov/pubmed/23892221", "http://www.ncbi.nlm.nih.gov/pubmed/21159787" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055948", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011315" ]

[ "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins.", "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins ", "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins" ]

[ "mpMoRFsDB" ]

[ "mpMoRFsDB: a database of molecular recognition features in membrane proteins", "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins", "mpMoRFsDB: a database of molecular recognition features in membrane proteins." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24093637", "http://www.ncbi.nlm.nih.gov/pubmed/23894139", "http://www.ncbi.nlm.nih.gov/pubmed/23328413" ]

[]

[]

[ "LepChorionDB" ]

[ "LepChorionDB" ]

[ "LepChorionDB, a database of Lepidopteran chorion proteins and a set of tools useful for the identification of chorion proteins in Lepidopteran proteomes", "A database, named LepChorionDB, was constructed by searching 5 different protein databases using class A and B central domain-specific profile Hidden Markov Models (pHMMs), developed in this work. A total of 413 Lepidopteran chorion proteins from 9 moths and 1 butterfly species were retrieved. These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes. LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins", "LepChorionDB, a database of Lepidopteran chorion proteins and a set of tools useful for the identification of chorion proteins in Lepidopteran proteomes.", "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes.", "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins.", "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes.", "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins.", "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes", "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23262288" ]

[]

[]

[ "Yes" ]

[ "yes" ]

[ "To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome.", "The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial.", "Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data", "Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover", "The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial.", "The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. ", " The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks ", "Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,", "Single clinical trials have found no benefit for dong quai, evening primrose oil,", "Single clinical trials have found that dong quai, evening primrose oil,", "To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17593379", "http://www.ncbi.nlm.nih.gov/pubmed/12435217", "http://www.ncbi.nlm.nih.gov/pubmed/8136666", "http://www.ncbi.nlm.nih.gov/pubmed/14716179", "http://www.ncbi.nlm.nih.gov/pubmed/23625331", "http://www.ncbi.nlm.nih.gov/pubmed/20979541", "http://www.ncbi.nlm.nih.gov/pubmed/16753687", "http://www.ncbi.nlm.nih.gov/pubmed/15292498" ]

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"http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00000559", "o": "http://data.linkedct.org/resource/condition/10439" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00000559", "o": "Trial NCT00000559" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00000532", "o": "http://data.linkedct.org/resource/condition/10439" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00000532", "o": "Trial NCT00000532" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00745173", "o": "http://data.linkedct.org/resource/condition/10439" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00745173", "o": "Trial NCT00745173" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00006539", "o": "http://data.linkedct.org/resource/condition/10439" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00006539", "o": "Trial NCT00006539" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00010712", "o": "http://data.linkedct.org/resource/condition/10439" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00010712", "o": "Trial NCT00010712" }, { "p": "http://data.linkedct.org/resource/linkedct/nct_alias", "s": "http://data.linkedct.org/resource/trials/NCT00010712", "o": "NCT00009386" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00554255", "o": "http://data.linkedct.org/resource/condition/10436" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/10436", "o": "Condition #10436 (Postmenopausal Women)" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/10436", "o": "Postmenopausal Women" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00554255", "o": "Trial NCT00554255" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00577720", "o": "http://data.linkedct.org/resource/condition/10436" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00577720", "o": "Trial NCT00577720" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00235586", "o": "http://data.linkedct.org/resource/condition/10436" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00235586", "o": "Trial NCT00235586" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00566553", "o": "http://data.linkedct.org/resource/condition/10436" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00566553", "o": "Trial NCT00566553" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004042", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D031825", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D031665", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016449", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017698" ]

[ "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))", "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme acid α-glucosidase (GAA), responsible for degradation of lysosomal glycogen." ]

[ "yes" ]

[ "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))", "Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation", "Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid α-glucosidase (GAA)", "Acid α-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available", "The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase.", "Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase.", "Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness.", "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types.", "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene.", "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen.", "Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA).", "Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method.", "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists.", "Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy.", "Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease.", "Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase.", "Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease.", "The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease", "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease", "Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme", "Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease", "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types", "As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter", "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome", "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene", "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen", "Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme.", "Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease.", "Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers.", "The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease.", "Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. ", "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease).", "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,", " Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function.", " Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy.", "Pompe disease is caused by the congenital deficiency of the lysosomal enzyme acid alpha-glucosidase.", "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,", " Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs.", "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists.", "Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase.", "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome.", "Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease.", "Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA).", "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease.", "Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder.", "Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase.", "Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18648322", "http://www.ncbi.nlm.nih.gov/pubmed/25256446", "http://www.ncbi.nlm.nih.gov/pubmed/26029718", "http://www.ncbi.nlm.nih.gov/pubmed/14643388", "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "http://www.ncbi.nlm.nih.gov/pubmed/8935410", "http://www.ncbi.nlm.nih.gov/pubmed/19343043", "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "http://www.ncbi.nlm.nih.gov/pubmed/20206419", "http://www.ncbi.nlm.nih.gov/pubmed/15639117", "http://www.ncbi.nlm.nih.gov/pubmed/25217571", "http://www.ncbi.nlm.nih.gov/pubmed/8552676", "http://www.ncbi.nlm.nih.gov/pubmed/19862843", "http://www.ncbi.nlm.nih.gov/pubmed/19371716", "http://www.ncbi.nlm.nih.gov/pubmed/15585405", "http://www.ncbi.nlm.nih.gov/pubmed/9505277", "http://www.ncbi.nlm.nih.gov/pubmed/19775921", "http://www.ncbi.nlm.nih.gov/pubmed/11468225", "http://www.ncbi.nlm.nih.gov/pubmed/25036864", "http://www.ncbi.nlm.nih.gov/pubmed/17095274", "http://www.ncbi.nlm.nih.gov/pubmed/9668092", "http://www.ncbi.nlm.nih.gov/pubmed/25786784", "http://www.ncbi.nlm.nih.gov/pubmed/9883081", "http://www.ncbi.nlm.nih.gov/pubmed/11906", "http://www.ncbi.nlm.nih.gov/pubmed/12409258" ]

[]

[]

[ "Tripolin A reduced the localization of pAurora A on spindle microtubules (MTs), affected centrosome integrity, spindle formation and length, as well as MT dynamics in interphase, consistent with Aurora A inhibition by RNAi or other specific inhibitors, such as MLN8054 or MLN8237. Interestingly, Tripolin A affected the gradient distribution towards the chromosomes, but not the MT binding of HURP (Hepatoma Up-Regulated Protein), a MT-associated protein (MAP) and substrate of the Aurora A kinase. Therefore Tripolin A reveals a new way of regulating mitotic MT stabilizers through Aurora A phosphorylation. Mitotic regulators exhibiting gain of function in tumor cells are considered useful cancer therapeutic targets for the development of small-molecule inhibitors.", "Tripolin A inhibits Aurora A kinase activity both in vitro and in human cells." ]

[ "Aurora A" ]

[ "Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules.", "The human Aurora kinases are a family of such targets. In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor. ", "In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro", "Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP&apos;s distribution on microtubules", "In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23516487" ]

[]

[]

[ "Channelrhodospin-2 (ChR2) is a light-sensitive ion channel that has emerged as new optogenetics tool." ]

[ "yes" ]

[ "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology.", "Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination.", "Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model.", "The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization.", "Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer the ability to use light stimulation to regulate neural activity with millisecond precision.", "The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive.", "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. ", "Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales. ", "Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. ", "Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. ", "Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). ", "The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization.", "The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive. A light-triggered action potential or light-driven perturbations of ongoing electrical activity provide instant voltage feedback, shaping ChR2 current.", " Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales.", "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology.", "It allows neurons to express light-sensitive genes that enable the identification, dissection, and manipulation of specific neural populations and their connections in the tissues and organs of awake animals with unprecedented spatial and temporal precision. Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination.", "Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. The molecular mechanism of ChR2 has been extensively studied by a variety of spectroscopic methods, including light-induced difference Fourier transform infrared (FTIR) spectroscopy, which is sensitive to structural changes in the protein upon light activation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25571406", "http://www.ncbi.nlm.nih.gov/pubmed/23664865", "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "http://www.ncbi.nlm.nih.gov/pubmed/23002710", "http://www.ncbi.nlm.nih.gov/pubmed/23380919", "http://www.ncbi.nlm.nih.gov/pubmed/23366158", "http://www.ncbi.nlm.nih.gov/pubmed/25518365", "http://www.ncbi.nlm.nih.gov/pubmed/25060859", "http://www.ncbi.nlm.nih.gov/pubmed/25796616", "http://www.ncbi.nlm.nih.gov/pubmed/23056472", "http://www.ncbi.nlm.nih.gov/pubmed/24026336", "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "http://www.ncbi.nlm.nih.gov/pubmed/24022017", "http://www.ncbi.nlm.nih.gov/pubmed/25483880", "http://www.ncbi.nlm.nih.gov/pubmed/24555016", "http://www.ncbi.nlm.nih.gov/pubmed/24518144", "http://www.ncbi.nlm.nih.gov/pubmed/24509078" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062308" ]

[ "No, although the PSA test can detect high levels of PSA that may indicate the presence of prostate cancer, many other conditions, such as an enlarged or inflamed prostate, can also increase PSA levels." ]

[ "no" ]

[ "rostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer death in men", "PSA is known to be prostate specific, but not PCa specific", "deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are well recognized.", "medical debate surrounding the use of the prostate-specific antigen (PSA) test for prostate cancer screening", "The clinical relevance of this surprisingly high rate of prostate cancer in men with a normal PSA is yet to be determined ", "Rapid uptake of prostate-specific antigen (PSA) testing has occurred in the United States despite inconclusive evidence regarding mortality benefit", "Routine cancer screening with prostate-specific antigen (PSA) is controversial, and practice guidelines recommend that men be counseled about its risks and benefits", "Prostate carcinoma was histologically confirmed in 14 (0.66%) of the men, nine times in the early stage (T2) and five times in the clinical stage (T3), corresponding to an incidence of circa 650 cases per 100,000 men in the target age group", "This newly developed PSA test system can enhance the acceptance rate and effectiveness of medical check-ups for prostate cancer,", "PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease", "PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points", "have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12088291", "http://www.ncbi.nlm.nih.gov/pubmed/9494603", "http://www.ncbi.nlm.nih.gov/pubmed/7544735", "http://www.ncbi.nlm.nih.gov/pubmed/24223021", "http://www.ncbi.nlm.nih.gov/pubmed/18808732", "http://www.ncbi.nlm.nih.gov/pubmed/9494604", "http://www.ncbi.nlm.nih.gov/pubmed/20065953", "http://www.ncbi.nlm.nih.gov/pubmed/15530599", "http://www.ncbi.nlm.nih.gov/pubmed/9329582", "http://www.ncbi.nlm.nih.gov/pubmed/17559560", "http://www.ncbi.nlm.nih.gov/pubmed/15925651", "http://www.ncbi.nlm.nih.gov/pubmed/11583357", "http://www.ncbi.nlm.nih.gov/pubmed/7687205", "http://www.ncbi.nlm.nih.gov/pubmed/23588999", "http://www.ncbi.nlm.nih.gov/pubmed/17489318", "http://www.ncbi.nlm.nih.gov/pubmed/23400279", "http://www.ncbi.nlm.nih.gov/pubmed/18355899", "http://www.ncbi.nlm.nih.gov/pubmed/18569246", "http://www.ncbi.nlm.nih.gov/pubmed/17233806", "http://www.ncbi.nlm.nih.gov/pubmed/19579539", "http://www.ncbi.nlm.nih.gov/pubmed/10697616" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.uniprot.org/uniprot/KLK3_MACFA", "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.disease-ontology.org/api/metadata/DOID:10286", "http://www.uniprot.org/uniprot/KLK3_MACMU", "http://www.uniprot.org/uniprot/KLK3_HUMAN" ]

[ "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence." ]

[ "dementia", "gait disturbances", "urinary incontinence" ]

[ "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence.", "Normal pressure hydrocephalus (NPH) is a clinical triad of gait disturbance, dementia, and urinary incontinence combined with radiographic findings of ventriculomegaly and laboratory findings of normal cerebrospinal fluid pressures. Although it was first described by Hakim and Adams in 1965, there is no formal definition of NPH, causing discrepancy in its incidence in various studies. ", "INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a chronic neurological disorder characterized by enlarged ventricles and a triad of clinical symptoms affecting gait, cognition, and urinary continence. Salomón Hakim first identified the syndrome in 1957 at the Hospital San Juan de Dios in Bogotá, Colombia. ", "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment.", "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment.", "Chronic (normotensive or low pressure) hydrocephalus is characterized clinically by gait disturbance, cognitive and urinary impairment, known as Hakim's triad.", "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence", "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment", "BACKGROUND: Chronic (normotensive or low pressure) hydrocephalus is characterized clinically by gait disturbance, cognitive and urinary impairment, known as Hakim's triad. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19823916", "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "http://www.ncbi.nlm.nih.gov/pubmed/21194654", "http://www.ncbi.nlm.nih.gov/pubmed/20568668" ]

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[]

[ "The specific cellular target of Gefitinib (Iressa) is the epidermal growth factor receptor (EGFR)." ]

[ "Epidermal growth factor receptor (EGFR)" ]

[ "Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines.", "Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor.", "Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) that causes growth delay in cancer cell lines and human tumor xenografts expressing high levels of EGFR." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19276163", "http://www.ncbi.nlm.nih.gov/pubmed/18089711", "http://www.ncbi.nlm.nih.gov/pubmed/23255952" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058990", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016503", "http://www.biosemantics.org/jochem#4274201", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011958", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005006", "http://www.uniprot.org/uniprot/EGFR_CHICK" ]

[ "cystine disulfide bonds\namide bonds\nhydrogen bonds" ]

[ "cystine disulfide bonds", "amide bonds", "hydrogen bonds" ]

[ " Feathers and hair consist of cornified epidermal keratinocytes in which proteins are crosslinked via disulfide bonds between cysteine residues of structural proteins to establish mechanical resilience.", " The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in keratin", "ossible chemical bonds formed between alpha-keratins and KAbetaPs may derive from electrostatic interactions in addition to cross-linking through disulphide bonds.", "The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in the keratin", "e solubility test in the dithiothreitol/urea extraction buffer, the amino acid composition analysis and studies on keratin secondary structures suggest that the improved stability in water of thermally treated mats can be ascribed to the formation of amide bonds between acid and basic groups of some amino acid side chains.", "s the energy involved in the formation of disulfide bonds is much greater than that of hydrogen bonds or van der Waals interactions the structural transition is likely to be dominated by the requirement that the bonded cysteine residues occur at closely equivalent axial positions.", "The interface of the K5-K14 coiled-coil heterodimer has asymmetric salt bridges, hydrogen bonds and hydrophobic contacts, and its surface exhibits a notable charge polarization. A trans-dimer homotypic disulfide bond involving Cys367 in K14's stutter region occurs in the crystal and in skin keratinocytes, where it is concentrated in a keratin filament cage enveloping the nucleus. ", " the alpha helices which are stabilized by hydrogen bonds and the alpha-helical coiled coils which are stabilized by hydrophobic interactions, is more sensitive to radiation than the supramolecular architecture of the keratin filament and the filament packing within the keratin associated proteins matrix, which is stabilized by disulphide bonds.", ". A good solvent attacks the disulfide bonds between cystine molecules and hydrates the hair shaft." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24276370", "http://www.ncbi.nlm.nih.gov/pubmed/19925868", "http://www.ncbi.nlm.nih.gov/pubmed/24971553", "http://www.ncbi.nlm.nih.gov/pubmed/24367993", "http://www.ncbi.nlm.nih.gov/pubmed/23466495", "http://www.ncbi.nlm.nih.gov/pubmed/25947341", "http://www.ncbi.nlm.nih.gov/pubmed/22705788", "http://www.ncbi.nlm.nih.gov/pubmed/19412554", "http://www.ncbi.nlm.nih.gov/pubmed/22683767" ]

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[ "Moebius syndrome is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius syndrome with autism spectrum disorders (ASDs) has been suggested in early studies with heterogenous age groups." ]

[ "yes" ]

[ "The diagnosis of Moebius syndrome, a rare congenital disorder, is primarily based on congenital facial and abducent nerve palsy. Involvement of other cranial nerves is also common. Occasionally the V, X, XI, and XII cranial nerves are involved, resulting in a difficulty to chew, swallow, and cough, which often leads to respiratory complications. Mental retardation and autism have been reported in some cases", "Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups", "Certain genetic syndromes are providing us with extremely valuable information about the role played by genetics in autism. This is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome, 15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome, mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito, neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome.", "Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder", "Fifty-nine cases with infantile autism/autistic disorder were subclassified according to associated medical condition (fragile-X, tuberous sclerosis, neurofibromatosis, hypo-melanosis of Ito, Moebius syndrome, Rett syndrome, and a 'new' syndrome associated with a marker chromosome).", "Autism spectrum disorders in children and adolescents with Moebius sequence.", "Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought.", "A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups.", "Autistic behaviour in Moebius syndrome.", "The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level.", "Autism spectrum disorders in children and adolescents with Moebius sequence.", "Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought.", "Autistic behaviour in Moebius syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15736079", "http://www.ncbi.nlm.nih.gov/pubmed/22832772", "http://www.ncbi.nlm.nih.gov/pubmed/20621443", "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "http://www.ncbi.nlm.nih.gov/pubmed/1623312", "http://www.ncbi.nlm.nih.gov/pubmed/2929356" ]

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[]

[ "Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR) and it is a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure. Sarcolipin is a key regulator of SERCA2a in atria.", "Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport.Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure." ]

[ "yes" ]

[ "The activity of SERCA is regulated by two small, homologous membrane proteins called phospholamban (PLB, also known as PLN) and sarcolipin (SLN). Detailed structural information explaining this regulatory mechanism has been lacking, and the structural features defining the pathway through which cytoplasmic Ca(2+) enters the intramembranous binding sites of SERCA have remained unknown.", "Sarco(endo)plasmic reticulum Ca(2+)ATPase (SERCA) pump activity is modulated by phospholamban (PLB) and sarcolipin (SLN) in cardiac and skeletal muscle. Recent data suggest that SLN could play a role in muscle thermogenesis by promoting uncoupling of the SERCA pump", "Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, is necessary for muscle-based thermogenesis.", "Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure.", "Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and its expression is altered in diseased atrial myocardium.", "Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca(2+) load, which, in turn, could cause abnormal intracellular Ca(2+) handling and atrial remodeling.", "Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps.", "These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.", "The SERCA pump was constitutively activated in both atrial and ventricular chambers of the mouse heart by ablating its key regulators, phospholamban (PLN) and sarcolipin (SLN). The double-knockout (dKO) mice for PLN and SLN showed increased SERCA pump activity, Ca(2+) transients and SR Ca(2+) load, and developed cardiac hypertrophy.", "Our findings also emphasize the need for dynamic regulation of the SERCA pump by PLN and/or SLN to maintain cardiac contractility in normal conditions and during pathophysiological states.", "Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport.", "The inhibitory effect of SLN on cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by beta-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. ", "Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria.", "Our study documented that sarcolipin is a key regulator of SERCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.", "Sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) is a membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin (SLN), and all these proteins participate in maintaining the normal intracellular calcium handling. ", "Sarcolipin (SLN) is an integral membrane protein that is expressed in both skeletal and cardiac muscle, where it inhibits SERCA (calcium ATPase) by lowering its apparent Ca2+ affinity in a manner similar to that of its homologue phospholamban (PLN).", "Remarkably, each domain of SLN behaves in a manner similar to that of the corresponding domains in PLN, supporting the hypothesis that both SLN and PLN bind SERCA in the same groove and with similar mechanisms.", "The role of sarcolipin (SLN) in cardiac physiology was critically evaluated by generating a transgenic (TG) mouse model in which the SLN to sarco(endoplasmic)reticulum (SR) Ca(2+) ATPase (SERCA) ratio was increased in the ventricle. Overexpression of SLN decreases SR calcium transport function and results in decreased calcium transient amplitude and rate of relaxation. SLN TG hearts exhibit a significant decrease in rates of contraction and relaxation when assessed by ex vivo work-performing heart preparations.", "We conclude that SLN is a novel regulator of SERCA pump activity, and its inhibitory effect can be reversed by beta-adrenergic agonists.", "Sarcolipin, a homologue of phospholamban, regulates Ca2+ uptake through the interaction with sarcoplasmic reticulum Ca2+ ATPase (SERCA) and is predominantly expressed in the atrial muscle.", "Sarcolipin (SLN) and phospholamban (PLN) are effective inhibitors of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). ", "These results show that NF-SLN expression impairs muscle contractile function by inhibiting SERCA function and diminishing sarcoplasmic reticulum Ca(2+) stores.", "Sarcolipin (SLN) is an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs) in vitro, but its function in vivo has not been defined. NF-SLN cDNA (SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus muscle in one hindlimb by plasmid injection and electrotransfer.", "Sarcolipin (SLN), a regulator of the sarco(endo)plasmic reticulum Ca(2+)-ATPase of fast-twitch skeletal muscle (SERCA1a), is also expressed in cardiac and slow-twitch skeletal muscles where phospholamban (PLN) and SERCA2a are expressed.", "Sarco(endo)plasmic reticulum calcium ATPase (SERCA) inhibition by sarcolipin is encoded in its luminal tail.", "The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is regulated in a tissue-dependent manner via interaction with the short integral membrane proteins phospholamban (PLN) and sarcolipin (SLN).", "Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation.", "The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is regulated in a tissue-dependent manner via interaction with the short integral membrane proteins phospholamban (PLN) and sarcolipin (SLN)", "[Research progress of sarcolipin-a new regulatory protein of sarcoplasmic reticulum Ca2+ ATPase].", "Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation", "Sarcolipin (SLN) is an integral membrane protein that is expressed in both skeletal and cardiac muscle, where it inhibits SERCA (calcium ATPase) by lowering its apparent Ca2+ affinity in a manner similar to that of its homologue phospholamban (PLN)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16519897", "http://www.ncbi.nlm.nih.gov/pubmed/17515962", "http://www.ncbi.nlm.nih.gov/pubmed/18081313", "http://www.ncbi.nlm.nih.gov/pubmed/16036219", "http://www.ncbi.nlm.nih.gov/pubmed/20833651", "http://www.ncbi.nlm.nih.gov/pubmed/12032137", "http://www.ncbi.nlm.nih.gov/pubmed/22561503", "http://www.ncbi.nlm.nih.gov/pubmed/22496245", "http://www.ncbi.nlm.nih.gov/pubmed/12237298", "http://www.ncbi.nlm.nih.gov/pubmed/16365042", "http://www.ncbi.nlm.nih.gov/pubmed/17971438", "http://www.ncbi.nlm.nih.gov/pubmed/23362265", "http://www.ncbi.nlm.nih.gov/pubmed/19631655", "http://www.ncbi.nlm.nih.gov/pubmed/15556994", "http://www.ncbi.nlm.nih.gov/pubmed/22961106", "http://www.ncbi.nlm.nih.gov/pubmed/23455424", "http://www.ncbi.nlm.nih.gov/pubmed/21697544", "http://www.ncbi.nlm.nih.gov/pubmed/23341466" ]

[]

[ "http://www.biosemantics.org/jochem#4264789", "http://www.uniprot.org/uniprot/SARCO_MOUSE", "http://www.uniprot.org/uniprot/SARCO_HUMAN", "http://www.uniprot.org/uniprot/SARCO_RAT", "http://www.uniprot.org/uniprot/SARCO_RABIT", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498" ]

[ "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia.", "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia " ]

[ "At least 15%, based on the International Fanconi Anemia Registry (IFAR)" ]

[ "Sixteen of the 59 FA-C patients (27%) have developed acute myelogenous leukemia", "Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age", "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia", "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8068955", "http://www.ncbi.nlm.nih.gov/pubmed/9207444", "http://www.ncbi.nlm.nih.gov/pubmed/1548931" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://www.disease-ontology.org/api/metadata/DOID:8692", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015470", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007951" ]

[ "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)." ]

[ "One" ]

[ "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. ", "The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. ", "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. ", " Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. ", "The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. ", "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "http://www.ncbi.nlm.nih.gov/pubmed/22038757", "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "http://www.ncbi.nlm.nih.gov/pubmed/23378035" ]

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It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes." }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/id/C0010278" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11993001", "o": "CRS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18466196", "o": "Craniostenoses" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12007160", "o": "CRANIOSYNOSTOSIS, TYPE 1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17867080", "o": "Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447707", "o": "Craniosynostosis Plagiocephalies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0476812", "o": "craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469337", "o": "Synostotic Plagiocephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8356736", "o": "Premature closure of cranial sutures" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11935450", "o": "CRS1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457001", "o": "Craniostenosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447706", "o": "Plagiocephaly, Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18463141", "o": "Plagiocephaly, Synostotic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18460116", "o": "Plagiocephalies, Synostotic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0398432", "o": "CRANIOSYNOSTOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17990682", "o": "Craniosynostoses" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469338", "o": "Craniosynostosis Plagiocephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18450823", "o": "Synostotic Plagiocephalies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12007161", "o": "CRANIOSTENOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18014478", "o": "Craniosynostoses [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457000", "o": "Plagiocephalies, Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1305187", "o": "synostosis (cranial)" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/relation/R60595703" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11978039" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11978039", "o": "MUENKE SYNDROME, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11978039" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11992529", "o": "FGFR3, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11992529" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/relation/R60667887" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/relation/R60508185" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/omim", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "http://bio2rdf.org/omim:134934" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "Muenke syndrome, 602849" } ]

[ "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:225" ]

[ "The detection of fetal RhD status can be achieved with the non-invasive method of assessing free fetal DNA in the maternal blood." ]

[ "free fetal DNA from maternal cirulcation" ]

[ "Determination of fetal rhesus d status by maternal plasma DNA analysis.", "In this study, we assessed the feasibility of fetal RhD genotyping by analysis of cell-free fetal DNA(cffDNA) extracted from plasma samples of Rhesus (Rh) D-negative pregnant women by using real-time polymerase chain reaction (PCR).", "Performing real-time PCR on cffDNA showed accurate, efficient and reliable results, allowing rapid and high throughput non invasive determination of fetal sex and RhD status in clinical samples", "Non-invasive prenatal diagnosis of fetal RhD by using free fetal DNA", "The aim of this study is to determine fetal RhD status in the Rh incompatible pregnancies with an non-invasive technique; free fetal DNA isolation from maternal circulation.", " The detection of fetal RhD status by using a non-invasive method from maternal circulation was found to be possible. Assessing fetal RhD status non-invasively by using free fetal DNA in maternal blood will be cost-efficient, avoiding unnecessary indirect Coombs test and unnecessary Rhogam applications that is used in RH incompatible pregnancies.", "Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection.", "Non-invasive antenatal diagnosis of fetal rhesus status in an alloimmunised patient.", "Our subsequent investigations have shown that this elevation in fetal cell traffic may serve as an early marker for those pregnancies at risk for this disorder.A very recent exciting discovery has been that free extracellular fetal DNA can be detected in the plasma and serum of pregnant women, which may permit the rapid and accurate detection of uniquely fetal loci, such as the fetal rhesus D gene in rhesus D negative pregnant women.", "Fetal rhesus D (RhD) status determination using circulating cell-free fetal DNA from maternal plasma or serum is now recognized in Europe as a reliable and useful tool.", "NGS is now sufficiently sensitive to analyze circulating fetal DNA in maternal blood (cell-free fetal DNA, cffDNA), enabling applications such as non invasive diagnosis of fetal sex (and X-linked diseases), fetal rhesus among rhesus-negative women, trisomy and, in the near future, Mendelian mutations", "High throughput non-invasive determination of foetal Rhesus D status using automated extraction of cell-free foetal DNA in maternal plasma and mass spectrometry", "Non-invasive RNA-based determination of fetal Rhesus D type: a prospective study based on 96 pregnancies.", "BACKGROUND: Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. ", "Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection.", " Non-invasive prenatal diagnosis and testing by analysis of cell-free DNA in the maternal circulation is a rapidly evolving field. Current clinical applications include fetal sex determination, fetal rhesus D determination, the diagnosis of some single gene disorders, and a highly accurate screening test for aneuploidies." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25380024", "http://www.ncbi.nlm.nih.gov/pubmed/24778561", "http://www.ncbi.nlm.nih.gov/pubmed/21686347", "http://www.ncbi.nlm.nih.gov/pubmed/10985940", "http://www.ncbi.nlm.nih.gov/pubmed/24204719", "http://www.ncbi.nlm.nih.gov/pubmed/22386678", "http://www.ncbi.nlm.nih.gov/pubmed/26152007", "http://www.ncbi.nlm.nih.gov/pubmed/26140187", "http://www.ncbi.nlm.nih.gov/pubmed/24786470", "http://www.ncbi.nlm.nih.gov/pubmed/21075065", "http://www.ncbi.nlm.nih.gov/pubmed/18751991", "http://www.ncbi.nlm.nih.gov/pubmed/26259290", "http://www.ncbi.nlm.nih.gov/pubmed/21576416", "http://www.ncbi.nlm.nih.gov/pubmed/20938838", "http://www.ncbi.nlm.nih.gov/pubmed/23072857", "http://www.ncbi.nlm.nih.gov/pubmed/15980640", "http://www.ncbi.nlm.nih.gov/pubmed/21244652", "http://www.ncbi.nlm.nih.gov/pubmed/20482298", "http://www.ncbi.nlm.nih.gov/pubmed/18945714" ]

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[ "There are at least 6 genes which have been proposed as potential candidates of gene therapy in heart failure.\n1. Cardiac Sarco-Endoplasmic Reticulum Calcium ATPase 2A (SERCA2A)\n2. Inhibitor 1 (I-1) of Protein Phosphatase 1B\n3. Protein Phosphatase 1B (PP1B)\n4. Yes Associated Protein (YAP)\n5. Survivin\n6. S100A1" ]

[ "Sarco-Endoplasmic Reticulum Calcium ATPase 2A", "(SERCA2A)", "Inhibitor 1 of Protein Phosphatase 1B", "(I-1)", "Protein Phosphatase 1B", "(PP1B)", "Yes Associated Protein", "(YAP)", "Survivin", "S100A1" ]

[ "The molecular abnormalities underlying HF are discussed along with potential targets for gene therapy, focusing on SERCA2a.", "The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) ", "In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.", "therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI", "calcium up-regulation by AAV1/SERCA2a gene therapy is safe and of potential benefit in advanced heart failure patients. ", "Survivin gene therapy can attenuate the progression of LV systolic dysfunction in doxorubicin cardiomyopathy.", "Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure.", "The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new era for gene therapy for the treatment of heart failure.", "Our results present a strong rationale for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure.", "S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and animals, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium (Ca(2+)) handling in acutely and chronically failing hearts in small animal models.", "Use of gene therapy for heart failure is gaining momentum as a result of the recent successful completion of phase II of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, which showed clinical safety and efficacy of an adeno-associated viral vector expressing sarco-endoplasmic reticulum calcium ATPase (SERCA2a).", "The recent successful and safe completion of a phase 2 trial targeting the cardiac sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA2a) has the potential to open a new era for gene therapy for heart failure.", "The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) has the potential to open a new era for gene therapy in the treatment of heart failure.", "AIMS: Impaired myocardial sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) activity is a hallmark of failing hearts, and SERCA2a gene therapy improves cardiac function in animals and patients with heart failure (HF)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23281410", "http://www.ncbi.nlm.nih.gov/pubmed/24403316", "http://www.ncbi.nlm.nih.gov/pubmed/21775667", "http://www.ncbi.nlm.nih.gov/pubmed/24833660", "http://www.ncbi.nlm.nih.gov/pubmed/22558250", "http://www.ncbi.nlm.nih.gov/pubmed/22362515", "http://www.ncbi.nlm.nih.gov/pubmed/23307169", "http://www.ncbi.nlm.nih.gov/pubmed/25327883", "http://www.ncbi.nlm.nih.gov/pubmed/25023328", "http://www.ncbi.nlm.nih.gov/pubmed/24622121", "http://www.ncbi.nlm.nih.gov/pubmed/22548568", "http://www.ncbi.nlm.nih.gov/pubmed/22383712" ]

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[]

[ "DX-88 is investigational name of a drug Ecallantide, a 60-amino acid recombinant protein discovered through phage display technology, that is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute hereditary angioedema attacks." ]

[ "Ecallantide" ]

[ "Ecallantide (known as DX-88 previously), a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. ", "Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies.", "Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant).", "Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery.", "OBJECTIVE: Ecallantide (DX-88) is a potent and specific inhibitor of plasma kallikrein. ", "DX-88 (ecallantide), a 60-amino acid recombinant protein discovered through phage display technology, is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute HAE attacks.", "DX-88 or ecallantide, a potent and specific inhibitor of plasma kallikrein, achieved all primary and secondary efficacy end points in a placebo-controlled, double-blind, phase 3 study, with a second phase 3 study ongoing.", "DX-88 (ecallantide, Dyax Corp.) is a highly specific recombinant plasma kallikrein inhibitor that halts the production of bradykinin and can be dosed subcutaneously.", "DX-88 (ecallantide, Dyax Corp.) is a highly specific recombinant plasma kallikrein inhibitor that halts the production of bradykinin and can be dosed subcutaneously" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18467921", "http://www.ncbi.nlm.nih.gov/pubmed/19093699", "http://www.ncbi.nlm.nih.gov/pubmed/18220151", "http://www.ncbi.nlm.nih.gov/pubmed/21481442", "http://www.ncbi.nlm.nih.gov/pubmed/14572819", "http://www.ncbi.nlm.nih.gov/pubmed/21760740", "http://www.ncbi.nlm.nih.gov/pubmed/16916274", "http://www.ncbi.nlm.nih.gov/pubmed/18613770" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015507" ]

[ "Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT). Based on similarity of electrocardiographic features, bidirectional ventricular tachycardia has been considered a variant of long QT syndrome. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively. This \"ping pong\" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy." ]

[]

[ "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity. ", "Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively.", "When the heart rate exceeded the threshold for bigeminy at the first site in the His-Purkinje system, ventricular bigeminy developed, causing the heart rate to accelerate and exceed the threshold for bigeminy at the second site. Thus, the triggered beat from the first site induced a triggered beat from the second site. The triggered beat from the second site next reciprocated by inducing a triggered beat from the first site, and so forth. Bigeminy from two sites produced BVT, and that from three or more sites produced polymorphic VT.", "This \"ping pong\" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy.", "The BVT, in this case, was most likely due to myocardial ischema. The ethiology of published BVT cases are most commonly digitalis toxicity and rarely herbal aconitine poisoning, hypokalemic periodic paralysis, cathecolaminergic VT, myocarditis, and Anderson-Tawil syndrome.", "Bidirectional ventricular tachycardia (BVT), although a rare arrhythmia in the general population, is frequently observed in patients with Andersen-Tawil syndrome and long QT interval. However, the pharmacologic treatment of this arrhythmia remains unknown.", "This report suggests that flecainide can be effective in controlling BVT associated with Andersen-Tawil syndrome and indicates that the left ventricular dysfunction is secondary to the arrhythmia and not due to an associated phenotypic manifestation of the disorder.", "Based on similarity of electrocardiographic features, bidirectional ventricular tachycardia has been considered a variant of long QT syndrome.", "Double ventricular ectopic rhythms had bizarre abnormal QRS complexes of two different morphologies and were inscribed in opposite directions. Ectopic rhythms in each case had parasystolic characteristics. These observations suggest bifocal automaticity as a mechanism for bidirectional ventricular tachycardia.", "Bidirectional ventricular tachycardia, defined as the rapid alternation of the QRS complexes with successive opposing axial deviation, is a rare arrhythmia. In the rare cases which have undergone endocavitary investigations, an infrahisian origin has generally been proved. However, the mechanism of these tachycardias remains poorly understood and is discussed with respect to a new case.", "In the light of previously reported cases with documented endocavitary investigation and this new case, it seems possible to talk in terms of true \"bidirectional ventricular tachycardia\", a tachycardia whose mechanism is obscure but certainly not univocal.", "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity.", "BACKGROUND: Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity.", "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity", "Bidirectional ventricular tachycardia, defined as the rapid alternation of the QRS complexes with successive opposing axial deviation, is a rare arrhythmia", "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14556882", "http://www.ncbi.nlm.nih.gov/pubmed/6180691", "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "http://www.ncbi.nlm.nih.gov/pubmed/19682706", "http://www.ncbi.nlm.nih.gov/pubmed/1713403", "http://www.ncbi.nlm.nih.gov/pubmed/17655675" ]

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[ "Human L-Ferritin\nThe genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes\nHomozygosity for the T-allele of BTBD9 rs9296249\nMEIS1\nIntragenic guanosine triphosphate cyclohydrolase-1 duplication\nLRRK2 gene mutation" ]

[ "LRRK2 gene mutation", "Human L-Ferritin", "The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes", "Homozygosity for the T-allele of BTBD9 rs9296249", "MEIS1", "Intragenic guanosine triphosphate cyclohydrolase-1 duplication" ]

[ "We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). ", "The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes that have been previously associated with iron status and/or restless leg syndrome (RLS)", "Homozygosity for the T-allele of BTBD9 rs9296249 was associated with lower serum ferritin. ", "A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors.", " In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (P(nom)≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9", " This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated.", "Four family members developed dopa-responsive dystonia, with onset in their late teens, and subsequently developed restless leg syndrome and migraine. CONCLUSIONS: This is the first report of an intragenic guanosine triphosphate cyclohydrolase-1 duplication in a dopa-responsive dystonia family.", "To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5)", "We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our family with a rather homogeneous phenotype and very early disease onset represents a unique opportunity to further elucidate the genetic causes of the frequent restless leg syndrome.", "A case of restless leg syndrome in a family with LRRK2 gene mutation.", "The association between RLS and LRRK2 gene mutation may be casual, but it can hypothesized that RLS is a possible phenotypic presentation in PARK8." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21572129", "http://www.ncbi.nlm.nih.gov/pubmed/18032746", "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "http://www.ncbi.nlm.nih.gov/pubmed/21287604", "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "http://www.ncbi.nlm.nih.gov/pubmed/23227859" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012148" ]

[ "Yes. The circadian clock coordinates ribosome biogenesis. It influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation." ]

[ "yes" ]

[ "The circadian clock coordinates ribosome biogenesis.", "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.", "Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation", "The circadian clock coordinates ribosome biogenesis", "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation", "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23300384" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469688", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18451217", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18463493", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18448084", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18463494", "o": "D057906" } ]

[ "http://amigo.geneontology.org/amigo/term/GO:0042254", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057906" ]

[ "Yes, mutations in CALM underly IVF manifesting in childhood and adolescence." ]

[ "yes" ]

[ "We characterized a family presenting with a history of ventricular fibrillation (VF) and sudden death without ECG or echocardiographic abnormalities at rest. Two siblings died suddenly at the ages of 9 and 10 years, and another two were resuscitated from out-of-hospital cardiac arrest with documented VF at age 10 and 16, respectively. Exome sequencing identified a missense mutation affecting a highly conserved residue (p.Phe90Leu) in the CALM1 gene encoding calmodulin. This mutation was also carried by one of the sibs who died suddenly, for whom DNA was available. The mutation was present in the mother and in an sibling, both asymptomatic but displaying a marginally prolonged QT-interval during exercise. CONCLUSIONS: We identified a mutation in CALM1 underlying IVF manifesting in childhood and adolescence. The causality of the mutation is supported by previous studies demonstrating that Phe90 mediates the direct interaction of CaM with target peptides", "Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24076290", "http://www.ncbi.nlm.nih.gov/pubmed/11807557" ]

[]

[ "http://www.uniprot.org/uniprot/CALM_PARTE", "http://www.uniprot.org/uniprot/CALM_ANAPL", "http://www.uniprot.org/uniprot/CALM_PNECA", "http://www.uniprot.org/uniprot/CALM_BRYDI", "http://www.uniprot.org/uniprot/CALM_PFIPI", "http://www.uniprot.org/uniprot/CALM_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016277", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016278", "http://www.uniprot.org/uniprot/CALM_EMENI", "http://www.uniprot.org/uniprot/CALM_FAGSY", "http://www.uniprot.org/uniprot/CALM_PLEOS", "http://www.uniprot.org/uniprot/CALM_DANRE", "http://www.uniprot.org/uniprot/CALM_ASPOR", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002147", "http://www.uniprot.org/uniprot/CALM_MAIZE", "http://www.uniprot.org/uniprot/CALM_WHEAT", "http://www.uniprot.org/uniprot/CALM_HALOK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014693", "http://www.uniprot.org/uniprot/CALM_HORVU", "http://www.uniprot.org/uniprot/CALM_CTEID", "http://www.uniprot.org/uniprot/CALM_SOLLC", "http://www.uniprot.org/uniprot/CALM_CIOIN", "http://www.uniprot.org/uniprot/CALM_METSE", "http://www.uniprot.org/uniprot/CALM_BOVIN", "http://www.uniprot.org/uniprot/CALM_STIJA", "http://www.uniprot.org/uniprot/CALM_OREMO", "http://www.uniprot.org/uniprot/CALM_LOCMI", "http://www.uniprot.org/uniprot/CALM_SCHPO", "http://www.uniprot.org/uniprot/CALM_TRYCR", "http://www.uniprot.org/uniprot/CALM_XENLA", "http://www.uniprot.org/uniprot/CALM_DROME", "http://www.uniprot.org/uniprot/CALM_CAPAN", "http://www.uniprot.org/uniprot/CALM_PHYPO", "http://www.uniprot.org/uniprot/CALM_CHLRE", "http://www.uniprot.org/uniprot/CALM_HUMAN", "http://www.uniprot.org/uniprot/CALM_SACJA", "http://www.uniprot.org/uniprot/CALM_PYTSP", "http://www.uniprot.org/uniprot/CALM_PAXIN", "http://www.uniprot.org/uniprot/CALM_NEUCR", "http://www.uniprot.org/uniprot/CALM_TETPY", "http://www.uniprot.org/uniprot/CALM_ONCSP", "http://www.uniprot.org/uniprot/CALM_TRYBG", "http://www.uniprot.org/uniprot/CALM_TRYBB", "http://www.uniprot.org/uniprot/CALM_PATSP", "http://www.uniprot.org/uniprot/CALM_BLAEM", "http://www.uniprot.org/uniprot/CALM_TORCA", "http://www.uniprot.org/uniprot/CALM_EUPCH", "http://www.uniprot.org/uniprot/CALM_MALDO", "http://www.uniprot.org/uniprot/CALM_HELAN", "http://www.uniprot.org/uniprot/CALM_EPIAK", "http://www.uniprot.org/uniprot/CALM_PYUSP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016276", "http://www.uniprot.org/uniprot/CALM_ALEFU", "http://www.uniprot.org/uniprot/CALM_MACPY", "http://www.uniprot.org/uniprot/CALM_SPIOL", "http://www.uniprot.org/uniprot/CALM_CAEEL", "http://www.uniprot.org/uniprot/CALM_HETTR", "http://www.uniprot.org/uniprot/CALM_APLCA", "http://www.uniprot.org/uniprot/CALM_PHYIN", "http://www.uniprot.org/uniprot/CALM_ELEEL", "http://www.uniprot.org/uniprot/CALM_STRPU", "http://www.uniprot.org/uniprot/CALM_MAGO7", "http://www.uniprot.org/uniprot/CALM_PLECO", "http://www.uniprot.org/uniprot/CALM_PERFV", "http://www.uniprot.org/uniprot/CALM_YEAST", "http://www.uniprot.org/uniprot/CALM_KLULA", "http://www.uniprot.org/uniprot/CALM_COLTR", "http://www.uniprot.org/uniprot/CALM_RABIT", "http://www.uniprot.org/uniprot/CALM_DICDI", "http://www.uniprot.org/uniprot/CALM_MYXGL", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018497", "http://www.uniprot.org/uniprot/CALM_EUGGR", "http://www.uniprot.org/uniprot/CALM_PONAB", "http://www.uniprot.org/uniprot/CALM_STYLE", "http://www.uniprot.org/uniprot/CALM_KARMI", "http://www.uniprot.org/uniprot/CALM_RAT", "http://www.uniprot.org/uniprot/CALM_PLAFA", "http://www.uniprot.org/uniprot/CALM_TETTH", "http://www.uniprot.org/uniprot/CALM_AGABI", "http://www.uniprot.org/uniprot/CALM_STRIE", "http://www.uniprot.org/uniprot/CALM_AJECG", "http://www.uniprot.org/uniprot/CALM_GECJA", "http://www.uniprot.org/uniprot/CALM_SUBDO", "http://www.uniprot.org/uniprot/CALM_PROMN", "http://www.uniprot.org/uniprot/CALM_CANAX", "http://www.uniprot.org/uniprot/CALM_CHICK", "http://www.uniprot.org/uniprot/CALM_COLGL", "http://www.uniprot.org/uniprot/CALM_PLAF7", "http://www.uniprot.org/uniprot/CALM_LILLO", "http://www.uniprot.org/uniprot/CALM_MOUSC", "http://www.uniprot.org/uniprot/CALM_RENRE", "http://www.uniprot.org/uniprot/CALM_MOUSE", "http://www.uniprot.org/uniprot/CALM_ACHKL", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018487", "http://www.uniprot.org/uniprot/CALM_LYTPI", "http://www.uniprot.org/uniprot/CALM_MEDSA", "http://www.uniprot.org/uniprot/CALM_LUMRU" ]

[ "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies." ]

[ "piggyBac" ]

[ "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis. ", "We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. ", "However, recently another system known as PiggyBac (PB) has been introduced and developed for fulfilling the same purposes, for example, mutagenesis, transgenesis and gene therapy and in some cases with improved transposition efficiency and advantages over the Sleeping Beauty transposon system, although improved hyperactive transposase has highly increased the transposition efficacy for SB. ", "Here, we compared the efficiency of two different transposon systems, Sleeping Beauty (SB) and piggyBac (PB), for the generation of murine iPS. ", "However, recently another system known as PiggyBac (PB) has been introduced and developed for fulfilling the same purposes, for example, mutagenesis, transgenesis and gene therapy and in some cases with improved transposition efficiency and advantages over the Sleeping Beauty transposon system, although improved hyperactive transposase has highly increased the transposition efficacy for SB.", "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis.", "In this study, we compared the genomic integration efficiencies and transposition site preferences of Sleeping Beauty (SB or SB11), Tol2, and piggyBac (PB) transposon systems in primary T cells derived from peripheral blood lymphocytes (PBL) and umbilical cord blood (UCB). We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. ", "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis. Although Sleeping Beauty had no detectable genomic bias with respect to insertions in genes or intergenic regions, both Sleeping Beauty and PiggyBac transposons displayed preferential integration into actively transcribed loci.", "We have compared the chromosomal mobilization efficiency and insertion site preference of the two transposons mobilized from the same donor site in mouse embryonic stem (ES) cells under conditions in which there were no selective constraints on the transposons&apos; insertion sites. Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis.", "In this study we directly compared the genomic integration efficiencies of piggyBac, hyperactive Sleeping Beauty (SB11), Tol2, and Mos1 in four mammalian cell lines. piggyBac demonstrated significantly higher transposition activity in all cell lines whereas Mos1 had no activity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21516337", "http://www.ncbi.nlm.nih.gov/pubmed/17005721", "http://www.ncbi.nlm.nih.gov/pubmed/20606646", "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "http://www.ncbi.nlm.nih.gov/pubmed/17164785" ]

[]

[]

[ "Upon heat stress, TORC1 is recruited to stress granules." ]

[]

[ "Transient sequestration of TORC1 into stress granules during heat stress.", "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling", "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress", "TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress", "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.", "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. ", "Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.", "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling.", "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. Moreover, TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress.", "Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22727621" ]

[]

[]

[ "rivaroxaban undergoes renal metabolism" ]

[ "yes" ]

[ "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients.", "The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion.", "Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. ", "In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.", "Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower.", "However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. ", "Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. ", "Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23026665", "http://www.ncbi.nlm.nih.gov/pubmed/23631188", "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "http://www.ncbi.nlm.nih.gov/pubmed/22931521", "http://www.ncbi.nlm.nih.gov/pubmed/19712596", "http://www.ncbi.nlm.nih.gov/pubmed/19196845", "http://www.ncbi.nlm.nih.gov/pubmed/23652451", "http://www.ncbi.nlm.nih.gov/pubmed/22825670", "http://www.ncbi.nlm.nih.gov/pubmed/23790601" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007668", "http://www.biosemantics.org/jochem#4243836" ]

[ "Side effects of nalmefene include nausea, dizziness / lightheadedness, insomina, fatigue, vomiting, reduced caloric intake / apetite, increased self-rated alertness and decreased tiredness. In horses some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation has been described. In some studies nalmefene was well tolerated by all subjects, and no clinically significant adverse effects were observed." ]

[ "nausea", "dizziness / lightheadedness", "insomnia", "fatigue", "vomiting", "reduced caloric intake / apetite", "increased self-rated alertness", "decreased tiredness", "(horses) some passage of semifluid fecal material", "(horses) intermittent penile relaxation", "(horses) mild sedation" ]

[ "Adverse experiences included nausea, dizziness, and insomnia.", "Side effects to nalmefene were of greater duration and intensity in the subjects receiving 10 mg of nalmefene vs. those receiving 6 or 2 mg. These included most notably fatigue, lightheadedness, nausea and vomiting.", "The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. ", "Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self-rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour.", "In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.", " In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. ", "Doses of nalmefene as large as 0.4 mg/kg, IV, produced only minor side effects. These side effects included some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation. Treated horses responded normally to external stimuli, retained their appetites, and performed appropriately when ridden. Sedation wore off during the course of prolonged infusions. ", "The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16379031", "http://www.ncbi.nlm.nih.gov/pubmed/3826875", "http://www.ncbi.nlm.nih.gov/pubmed/3680580", "http://www.ncbi.nlm.nih.gov/pubmed/3943269", "http://www.ncbi.nlm.nih.gov/pubmed/2315439", "http://www.ncbi.nlm.nih.gov/pubmed/16449486" ]

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[ "http://www.biosemantics.org/jochem#4258016" ]

[ "Mowat-Wilson syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects.", "Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung s disease, intellectual disability, and prominent facial features are present ", "Yes. Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprungs disease, intellectual disability, and prominent facial features are present" ]

[ "yes" ]

[ "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects", "Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung's disease, intellectual disability, and prominent facial features are present", "Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene", "Mowat-Wilson syndrome is a genetic disease characterized by typical facial features, Hirschsprung disease and multiple congenital abnormalities", "Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR)", " The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum.", "\"Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects.", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations.", "BACKGROUND/PURPOSE: Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS).", "Severe clinical course of Hirschsprung disease in a Mowat-Wilson syndrome patient.", "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation.", "Mowat-Wilson syndrome is a genetic disease characterized by typical facial features, Hirschsprung disease and multiple congenital abnormalities.", "Supernumerary intestinal muscle coat in a patient with Hirschsprung disease/Mowat-Wilson syndrome.", "We present the 1st case report of an additional enteric smooth muscle layer in a patient with Mowat-Wilson syndrome and Hirschsprung disease.", "Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.", "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies.", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum", "Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies", "We present the 1st case report of an additional enteric smooth muscle layer in a patient with Mowat-Wilson syndrome and Hirschsprung disease", "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies", "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations", "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease", "Outcomes of Hirschsprung's disease associated with Mowat-Wilson syndrome.", "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "http://www.ncbi.nlm.nih.gov/pubmed/19302864", "http://www.ncbi.nlm.nih.gov/pubmed/24092421", "http://www.ncbi.nlm.nih.gov/pubmed/20158378", "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "http://www.ncbi.nlm.nih.gov/pubmed/23610866", "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "http://www.ncbi.nlm.nih.gov/pubmed/16150342", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "http://www.ncbi.nlm.nih.gov/pubmed/20145308", "http://www.ncbi.nlm.nih.gov/pubmed/23427518" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627" ]

[ "Functional annotation-based approaches and literature-based approaches have been initially used. In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization. Currently network-based methods are the ones most widely used." ]

[ "network-based methods" ]

[ "We developed a new network inference algorithm called the Knowledge Network Gene Prioritization (KNGP) algorithm which can incorporate both link and node knowledge", " In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization", "We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena", " We intend to use the ensemble boosting learning techniques to combine variant computational approaches for gene prioritization in order to improve the overall performance.", "The experimental results show that our ensemble learning approach outperforms the four gene-prioritization methods in ToppGene suite in the ranking results of the 13 known genes in terms of mean average precision, ROC and AUC measures", "The proposed enhanced RaJoLink rare-term model combines text mining and gene prioritization approaches.", " Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links", "Recently, many network-based methods have been proposed that implicitly utilize the modularity principle, which states that genes causing the same or similar diseases tend to form physical or functional modules in gene/protein relationship networks", "the random walk with restart (RWR) algorithm is considered to be a state-of-the-art approach, but the modularity principle has not been fully considered in traditional RWR approaches", "Therefore, we propose a novel method called ORIENT (neighbor-favoring weight reinforcement) to improve the performance of RWR through proper intensification of the weights of interactions close to the known disease genes", "Network-based methods have been successfully exploiting this concept by capturing the interaction of genes or proteins into a score", " Over the last years, computational approaches exploiting interaction network topology have been successfully applied to prioritize individual genes involved in diseases.", "Here, we propose a genome-wide network-based prioritization framework named GUILD", "The traditional approach to reduce the number of candidate genes entails fine-mapping studies using markers and pedigrees", "For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. ", "hus, comparing the similarity between experimentally identified phenotypes and the phenotypes associated with human diseases can be used to suggest causal genes underlying a disease. In this manuscript, we present a method for disease gene prioritization based on comparing phenotypes of mouse models with those of human diseases.", "We present biomarker identification problem using gene prioritization method called gene prioritization from microarray data based on shortest paths, extended with structural and biological properties and edge flux using voting scheme (GP-MIDAS-VXEF).", "ensemble approach to microarray data-based gene prioritization after missing value imputation", "Recently, we have introduced the data mining tool ENDEAVOUR (Aerts et al., 2006), which performs this task automatically by relying on different genome-wide data sources, such as Gene Ontology, literature, microarray, sequence and more", "So far, biologists have relied on literature studies, extensive queries to multiple databases and hunches about expected properties of the disease gene to determine such an ordering", "We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene http://toppgene.cchmc.org, outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOU", " Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization", "We use co-expression data from yeast (S. cerevisiae), nematode worm (C. elegans), fruit fly (D. melanogaster), mouse and human and find that the use of evolutionary conservation can indeed improve the predictive value of co-expression", "Using a training set of genes known to be involved in a biological process of interest, our approach consists of (i) inferring several models (based on various genomic data sources), (ii) applying each model to the candidate genes to rank those candidates against the profile of the known genes and (iii) merging the several rankings into a global ranking of the candidate genes", "vocabularies, representations and ranking algorithms for gene prioritization by text mining", "Recently, text mining techniques have been applied to extract prior knowledge from text-based genomic information sources and this knowledge can be used to improve the prioritization process", "We present an approach to prioritize single nucleotide polymorphisms for further follow-up in genome-wide association studies of type 2 diabetes", "The proposed method combines both the use of open data access from two type 2 diabetes-genome-wide association studies (granted by the Diabetes Genetics Initiative and the Welcome Trust Case Control Consortium) and the comprehensive analysis of candidate regions generated by the freely accessible ENDEAVOUR software.", "ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome.", "The protein-protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method)", "We present gene prioritization system (GPSy), a cross-species gene prioritization system that facilitates the arduous but critical task of prioritizing genes for follow-up functional analyses", "GPEC: a Cytoscape plug-in for random walk-based gene prioritization and biomedical evidence collection", "Among these, network-based approaches are recently proposed and outperformed functional annotation-based ones", "In the plug-in, gene prioritization is performed through a random walk with restart algorithm, a state-of-the art network-based method, along with a gene/protein relationship networ", "Here we present a multi-dimensional evidence-based candidate gene prioritization approach for complex diseases and demonstrate it in schizophrenia", "We present a multi-view approach to retrieve biomedical knowledge using different controlled vocabularies", "Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data", "Genomic linkage and association studies are commonly performed for identifying disease-related gene", "Here, we introduce MedSim, a novel approach for ranking candidate genes for a particular disease based on functional comparisons involving the Gene Ontology", "MedSim uses functional annotations of known disease genes for assessing the similarity of diseases as well as the disease relevance of candidate genes", "Here, we report a large-scale analysis of spatial, i.e. 3D, gene-expression data from an entire organ (the mouse brain) for the purpose of evaluating and ranking positional candidate genes, showing that the spatial gene-expression patterns can be successfully exploited for the prediction of gene-phenotype associations not only for mouse phenotypes, but also for human central nervous system-related Mendelian disorders", "In this paper, we propose an expandable framework for gene prioritization that can integrate multiple heterogeneous data sources by taking advantage of a unified graphic representation", "We demonstrate that existing methods are likely to favor highly connected genes, making prioritization sensitive to the skewed degree distribution of PPI networks, as well as ascertainment bias in available interaction and disease association data", "Motivated by this observation, we propose several statistical adjustment methods to account for the degree distribution of known disease and candidate genes, using a PPI network with associated confidence scores for interactions", "Here we employ a previously described method of candidate gene prioritization based mainly on gene annotation, in accompaniment with a technique based on the evaluation of pertinent sequence motifs or signatures, in an attempt to refine the gene prioritization approach.", "We introduce the novel Génie algorithm that overcomes these problems by evaluating the literature attached to all genes in a genome and to their orthologs according to a selected topic", "PINTA (available at http://www.esat.kuleuven.be/pinta/; this web site is free and open to all users and there is no login requirement) is a web resource for the prioritization of candidate genes based on the differential expression of their neighborhood in a genome-wide protein-protein interaction network", "We have recently developed a computational method for constitutional genetic disorders that identifies the most promising candidate genes by replacing prior knowledge by experimental data of differential gene expression between affected and healthy individual" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24260251", "http://www.ncbi.nlm.nih.gov/pubmed/23028459", "http://www.ncbi.nlm.nih.gov/pubmed/23434623", "http://www.ncbi.nlm.nih.gov/pubmed/17646288", "http://www.ncbi.nlm.nih.gov/pubmed/24110485", "http://www.ncbi.nlm.nih.gov/pubmed/23633938", "http://www.ncbi.nlm.nih.gov/pubmed/23185389", "http://www.ncbi.nlm.nih.gov/pubmed/22719993", "http://www.ncbi.nlm.nih.gov/pubmed/24219996", "http://www.ncbi.nlm.nih.gov/pubmed/18508807", "http://www.ncbi.nlm.nih.gov/pubmed/19346957", "http://www.ncbi.nlm.nih.gov/pubmed/21602267", "http://www.ncbi.nlm.nih.gov/pubmed/20840752", "http://www.ncbi.nlm.nih.gov/pubmed/21731658", "http://www.ncbi.nlm.nih.gov/pubmed/20823322", "http://www.ncbi.nlm.nih.gov/pubmed/19465376", "http://www.ncbi.nlm.nih.gov/pubmed/21609954", "http://www.ncbi.nlm.nih.gov/pubmed/22430954", "http://www.ncbi.nlm.nih.gov/pubmed/22570409", "http://www.ncbi.nlm.nih.gov/pubmed/23696895", "http://www.ncbi.nlm.nih.gov/pubmed/16680138", "http://www.ncbi.nlm.nih.gov/pubmed/17939863", "http://www.ncbi.nlm.nih.gov/pubmed/20576703", "http://www.ncbi.nlm.nih.gov/pubmed/23855662", "http://www.ncbi.nlm.nih.gov/pubmed/22808075", "http://www.ncbi.nlm.nih.gov/pubmed/21668950", "http://www.ncbi.nlm.nih.gov/pubmed/19602527", "http://www.ncbi.nlm.nih.gov/pubmed/21699738", "http://www.ncbi.nlm.nih.gov/pubmed/20823330", "http://www.ncbi.nlm.nih.gov/pubmed/22654636", "http://www.ncbi.nlm.nih.gov/pubmed/18689812", "http://www.ncbi.nlm.nih.gov/pubmed/17267438", "http://www.ncbi.nlm.nih.gov/pubmed/20074336", "http://www.ncbi.nlm.nih.gov/pubmed/22893106", "http://www.ncbi.nlm.nih.gov/pubmed/18433471" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722" ]

[ "When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly. Mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. Malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD)." ]

[ "Polycystic kidney disease (PKD)" ]

[ "role of primary cilia in autosomal dominant polycystic kidney disease", "Recent research has focused on defects in signaling mediated by the primary cilia as the causative factor in ADPKD", "Interestingly, primary cilia concentrate p75NTR receptors in their membranes and are abnormally structured/damaged in transgenic (Tg) AD‑model mice, which could impact on the adult neurogenesis occurring in the dentate gyrus's subgranular zone (SGZ) that is necessary for new memory encoding, thereby favouring typical AD cognitive decline", "malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD)", "While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects", "mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease", "Although Glis3(zf/zf) mice form normal primary cilia, renal cysts contain relatively fewer cells with a primary cilium", "When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly.", "Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease", "The cholangiociliopathies include but are not limited to cystic and fibrotic liver diseases associated with mutations", "Cysts in the kidney are among the most common inherited human pathologies, and recent research has uncovered that a defect in cilia-mediated signaling activity is a key factor that leads to cyst formation", "Multiple proteins whose functions are disrupted in cystic diseases have now been localized to the cilium or at the basal body at the base of the cilium", "Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts", "hus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas", "In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia.", "Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene", "The autosomal recessive polycystic kidney disease protein is localized to primary cilia", "It is proposed that the pathogenesis of autosomal recessive polycystic kidney disease is linked to the dysfunction of primary cilia" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19276629", "http://www.ncbi.nlm.nih.gov/pubmed/14978161", "http://www.ncbi.nlm.nih.gov/pubmed/19186246", "http://www.ncbi.nlm.nih.gov/pubmed/14983006", "http://www.ncbi.nlm.nih.gov/pubmed/21439862", "http://www.ncbi.nlm.nih.gov/pubmed/18407555", "http://www.ncbi.nlm.nih.gov/pubmed/23124509", "http://www.ncbi.nlm.nih.gov/pubmed/18694559", "http://www.ncbi.nlm.nih.gov/pubmed/15226261", "http://www.ncbi.nlm.nih.gov/pubmed/17429051", "http://www.ncbi.nlm.nih.gov/pubmed/19273592" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031514", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035058", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031512", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031513" ]

[ "Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales", "Ultraconserved elements and their flanking DNA are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis. Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales." ]

[]

[ "Target capture and massively parallel sequencing of ultraconserved elements for comparative studies at shallow evolutionary time scales", "Here, we evaluate the efficacy of genomic markers targeting ultraconserved DNA elements (UCEs) for analyses at shallow evolutionary timescales", "Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales", "A Phylogenomic Perspective on the Radiation of Ray-Finned Fishes Based upon Targeted Sequencing of Ultraconserved Elements (UCEs)", "Here, we provide a genomic perspective on longstanding questions regarding the diversification of major groups of ray-finned fishes through targeted enrichment of ultraconserved nuclear DNA elements (UCEs) and their flanking sequence. Our workflow efficiently and economically generates data sets that are orders of magnitude larger than those produced by traditional approaches and is well-suited to working with museum specimens. Analysis of the UCE data set recovers a well-supported phylogeny at both shallow and deep time-scales that supports a monophyletic relationship between Amia and Lepisosteus (Holostei) and reveals elopomorphs and then osteoglossomorphs to be the earliest diverging teleost lineages. Our approach additionally reveals that sequence capture of UCE regions and their flanking sequence offers enormous potential for resolving phylogenetic relationships within ray-finned fishes", "We applied a new phylogenomic approach to resolve relationships in Neoaves using target enrichment (sequence capture) and high-throughput sequencing of ultraconserved elements (UCEs) in avian genomes. We collected sequence data from UCE loci for 32 members of Neoaves and one outgroup (chicken) and analyzed data sets that differed in their amount of missing data", "More than 1000 ultraconserved elements provide evidence that turtles are the sister group of archosaurs", "A recent analysis of shared microRNA families found that turtles are more closely related to lepidosaurs. To test this hypothesis with data from many single-copy nuclear loci dispersed throughout the genome, we used sequence capture, high-throughput sequencing and published genomes to obtain sequences from 1145 ultraconserved elements (UCEs) and their variable flanking DNA. The resulting phylogeny provides overwhelming support for the hypothesis that turtles evolved from a common ancestor of birds and crocodilians, rejecting the hypothesized relationship between turtles and lepidosaurs", "Ultraconserved elements anchor thousands of genetic markers spanning multiple evolutionary timescales", "We introduce a new class of molecular marker, anchored by ultraconserved genomic elements (UCEs), that universally enable target enrichment and sequencing of thousands of orthologous loci across species separated by hundreds of millions of years of evolution. Our analyses here focus on use of UCE markers in Amniota because UCEs and phylogenetic relationships are well-known in some amniotes. We perform an in silico experiment to demonstrate that sequence flanking 2030 UCEs contains information sufficient to enable unambiguous recovery of the established primate phylogeny. We extend this experiment by performing an in vitro enrichment of 2386 UCE-anchored loci from nine, non-model avian species. We then use alignments of 854 of these loci to unambiguously recover the established evolutionary relationships within and among three ancient bird lineages. Because many organismal lineages have UCEs, this type of genetic marker and the analytical framework we outline can be applied across the tree of life, potentially reshaping our understanding of phylogeny at many taxonomic levels", "Ultraconserved elements are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis", "we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA. Using species-tree analysis that accounts for discord among hundreds of independent loci, we show that this class of marker is useful for recovering deep-level phylogeny in placental mammals", "One of the most remarkable findings of our study is that ultraconserved elements and their flanking DNA are a rich source of phylogenetic information with strong potential for application across Amniotes", "Ultraconserved elements are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis.", "Ultraconserved elements anchor thousands of genetic markers spanning multiple evolutionary timescales.", "Target capture and massively parallel sequencing of ultraconserved elements for comparative studies at shallow evolutionary time scales.", "Here, we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA.", "We applied a new phylogenomic approach to resolve relationships in Neoaves using target enrichment (sequence capture) and high-throughput sequencing of ultraconserved elements (UCEs) in avian genomes.", "We perform an in silico experiment to demonstrate that sequence flanking 2030 UCEs contains information sufficient to enable unambiguous recovery of the established primate phylogeny.", "Because many organismal lineages have UCEs, this type of genetic marker and the analytical framework we outline can be applied across the tree of life, potentially reshaping our understanding of phylogeny at many taxonomic levels.", "Here, we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22593086", "http://www.ncbi.nlm.nih.gov/pubmed/23824177", "http://www.ncbi.nlm.nih.gov/pubmed/23382987", "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "http://www.ncbi.nlm.nih.gov/pubmed/22232343" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010802" ]

[ "Treprostinil is a prostaglandin I(2) (PGI(2)) analog." ]

[ "Prostaglandin I(2)" ]

[ "We investigated the effects of 3 conventional (iloprost, beraprost, and treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1α expression in human monocytes.", "PGI(2) analogues (iloprost, treprostinil and beraprost) significantly increased IL-17A and IL-22 in vitro while decreasing IFNγ production both in SSc and HD PBMC.", "The effects of PGI(2) analogs iloprost and treprostinil on cytokine production, maturation and T-cell stimulatory function of human mDCs were investigated.", "Treprostinil, a stable prostacyclin analogue used in the treatment of pulmonary arterial hypertension, is in development as a sustained release oral tablet, treprostinil diolamine (United Therapeutics Corp, Research Triangle Park, NC)", "Treprostinil diolamine is an oral prostacyclin analogue; sustained release tablets of oral treprostinil are currently being evaluated for efficacy and safety as a potential therapy in patients with PAH", "Treprostinil diolamine (oral treprostinil) is a prostacyclin analogue under evaluation for the treatment for pulmonary arterial hypertension (PAH)", "Treprostinil diolamine (oral treprostinil) is a prostacyclin analogue currently being evaluated for the treatment of pulmonary arterial hypertension as a sustained-release (SR) oral tablet", "Treprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet", "Epoprostenol, a synthetic analogue of prostacyclin, and the chemically stable analogues iloprost, beraprost and treprostinil were tested in randomised controlled trials", "Treprostinil is a synthetic prostacyclin analogue with antiplatelet and vasodilatory properties", "Treprostinil is a stable analogue of prostacyclin, which can be administered subcutaneously, intravenously or by inhalation", "We recently showed that the stable prostacyclin analogue treprostinil, a clinically approved drug for pulmonary arterial hypertension (PAH), significantly reduced the recruitment of fibrocytes to sites of vascular remodeling in experimental hypoxic pulmonary hypertension. Here we report on the molecular mechanism underlying the inhibitory action of treprostinil on the adhesion and differentiation of human fibrocytes. Human fibrocytes expressed the prostanoid receptors, prostaglandin I (IP) receptors and prostaglandin E subtype receptors (EP2 and EP4). ", "Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease.", "Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.", "The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages.", "The prostacyclin analogues, iloprost and treprostinil are extensively used in treating pulmonary hypertension. ", "Iloprost (ILO) and treprostinil (TRP), two prostaglandin I2 analogues, were conjugated to fluorescein-labeled BSA (FLUO-BSA) and compared for IP1 receptor binding/uptake in different lung cell lines." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11897647", "http://www.ncbi.nlm.nih.gov/pubmed/22480736", "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "http://www.ncbi.nlm.nih.gov/pubmed/12082102", "http://www.ncbi.nlm.nih.gov/pubmed/23328389", "http://www.ncbi.nlm.nih.gov/pubmed/23597147", "http://www.ncbi.nlm.nih.gov/pubmed/17261956", "http://www.ncbi.nlm.nih.gov/pubmed/22814427", "http://www.ncbi.nlm.nih.gov/pubmed/23231023", "http://www.ncbi.nlm.nih.gov/pubmed/21278326", "http://www.ncbi.nlm.nih.gov/pubmed/20195728", "http://www.ncbi.nlm.nih.gov/pubmed/23429588", "http://www.ncbi.nlm.nih.gov/pubmed/21085923", "http://www.ncbi.nlm.nih.gov/pubmed/12437507", "http://www.ncbi.nlm.nih.gov/pubmed/23307827", "http://www.ncbi.nlm.nih.gov/pubmed/24402297", "http://www.ncbi.nlm.nih.gov/pubmed/20045181", "http://www.ncbi.nlm.nih.gov/pubmed/21400214", "http://www.ncbi.nlm.nih.gov/pubmed/17578162", "http://www.ncbi.nlm.nih.gov/pubmed/23927483", "http://www.ncbi.nlm.nih.gov/pubmed/24033615", "http://www.ncbi.nlm.nih.gov/pubmed/22231731", "http://www.ncbi.nlm.nih.gov/pubmed/18378784", "http://www.ncbi.nlm.nih.gov/pubmed/15920997", "http://www.ncbi.nlm.nih.gov/pubmed/23872196", "http://www.ncbi.nlm.nih.gov/pubmed/21185823", "http://www.ncbi.nlm.nih.gov/pubmed/15302727", "http://www.ncbi.nlm.nih.gov/pubmed/16253609", "http://www.ncbi.nlm.nih.gov/pubmed/12689580" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2784623", "o": "C427248" } ]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4270950", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011453", "http://www.biosemantics.org/jochem#4270950", "http://www.biosemantics.org/jochem#4276246" ]

[ "The Meier-Gorlin syndrome is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia or hypoplasia of the patellae, and severe pre- and postnatal growth retardation.", "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation ", "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation" ]

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[ "Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia", "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation", "The Meier-Gorlin syndrome or ear, patella, short stature syndrome (MIM 224690) is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia/hypoplasia of the patellae, and severe pre- and postnatal growth retardation", "Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears?⁻?.", "The Meier-Gorlin syndrome, or ear-patella-short stature syndrome, in sibs.", "Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS).", "The Meier-Gorlin syndrome or ear, patella, short stature syndrome (MIM 224690) is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia/hypoplasia of the patellae, and severe pre- and postnatal growth retardation.", "We report on an Italian boy with the Meier-Gorlin syndrome (ear-patella-short stature syndrome).", "Meier-Gorlin syndrome (ear-patella-short stature syndrome) in an Italian patient: clinical evaluation and analysis of possible candidate genes.", "The Meier-Gorlin syndrome (MGS) or ear, patella, short stature syndrome (MIM #224690) is a rare disorder with bilateral microtia, aplasia or hypoplasia of the patellae and severe intra-uterine and post-natal growth retardation.", "Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome).", "This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation.", "Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears�{�.", "Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae.", "While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome", "Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23144622", "http://www.ncbi.nlm.nih.gov/pubmed/21358631", "http://www.ncbi.nlm.nih.gov/pubmed/14564153", "http://www.ncbi.nlm.nih.gov/pubmed/21358632", "http://www.ncbi.nlm.nih.gov/pubmed/23023959", "http://www.ncbi.nlm.nih.gov/pubmed/7981855", "http://www.ncbi.nlm.nih.gov/pubmed/11477602", "http://www.ncbi.nlm.nih.gov/pubmed/11807867", "http://www.ncbi.nlm.nih.gov/pubmed/10213048", "http://www.ncbi.nlm.nih.gov/pubmed/25059018" ]

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[ "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity", "Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia." ]

[ "Beta glucocerebrosidase" ]

[ "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity", "Gaucher's disease is due to glucocerebrosidase deficiency which is responsible for the accumulation of non degraded glucosylceramide within the lysosomes of macrophages: these \"Gaucher cells\", overloaded and alternatively activated, release in patient's plasma numerous compounds (cytokines, chemokines, hydrolases...) some of which contribute to the various tissue damages", "Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a deficient activity of the lysosomal enzyme beta glucocerebrosidase", "Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia", "Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient", "The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology.", "Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls.", "It is an essential activator for glucocerebrosidase, the enzyme deficient in Gaucher disease.", "GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD).", "The gene for glucocerebrosidase ( GBA), the enzyme deficient in Gaucher disease, is located in a gene-rich region on 1q21.", "β-glucocerebrosidase, the enzyme deficient in Gaucher disease, also has an essential role in maintaining epidermal permeability function, by regulating the ratio of ceramides to glucosylceramides in the stratum corneum of the skin.", "Recently, it was recognized that mutations in the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are associated with an increased incidence of parkinsonism.", "Mutations in glucocerebrosidase (GBA), the enzyme deficient in Gaucher disease, are also identified at an increased frequency among Parkinson probands, including those of Ashkenazi Jewish ancestry.", "Structure/function relationships of acid beta-glucosidase, the enzyme deficient in Gaucher disease, were evaluated by characterizing the proteins expressed from cDNAs encoding normal and mutant enzymes.", "Gaucher disease is an autosomal recessive disorder resulting from deficient activity of the lysosomal enzyme glucocerebrosidase (GBA, E.C.3.2.1.45)", "GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD)", "LIMP-2 is required for the normal biogenesis and maintenance of lysosomes and endosomes and has been identified as the specific receptor for glucocerebrosidase, the enzyme deficient in Gaucher disease", "Mutations in glucocerebrosidase (GCase), the enzyme deficient in Gaucher disease, are a common genetic risk factor for the development of Parkinson disease and related disorders, implicating the role of this lysosomal hydrolase in the disease etiology", "This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease", "Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient activity of the enzyme glucocerebrosidase", "Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls", "The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology", "Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease.", "Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a deficiency of glucocerebrosidase.", "Gaucher's disease, the most prevalent of the sphingolipid storage disorders, is caused by a deficiency of the enzyme glucocerebrosidase (glucosylceramidase).", "Pathogenic variants in the glucocerebrosidase gene (GBA) encoding the enzyme deficient in Gaucher's disease (GD) are associated with Parkinson's disease (PD).", "Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a deficient activity of the lysosomal enzyme beta glucocerebrosidase.", "Recently, it was recognized that mutations in the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are associated with an increased incidence of parkinsonism.", "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity.", "Functional glucocerebrosidase is deficient in Gaucher's disease, an autosomal recessive lipid storage disorder that affects people of all ethnic backgrounds, but has a higher incidence among East European Jews (Ashkenazim).", "We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21982627", "http://www.ncbi.nlm.nih.gov/pubmed/20946052", "http://www.ncbi.nlm.nih.gov/pubmed/17644022", "http://www.ncbi.nlm.nih.gov/pubmed/18627336", "http://www.ncbi.nlm.nih.gov/pubmed/20945983", "http://www.ncbi.nlm.nih.gov/pubmed/22843412", "http://www.ncbi.nlm.nih.gov/pubmed/25429104", "http://www.ncbi.nlm.nih.gov/pubmed/8294487", "http://www.ncbi.nlm.nih.gov/pubmed/15024629", "http://www.ncbi.nlm.nih.gov/pubmed/20074983", "http://www.ncbi.nlm.nih.gov/pubmed/17433057", "http://www.ncbi.nlm.nih.gov/pubmed/15453048", "http://www.ncbi.nlm.nih.gov/pubmed/21653695", "http://www.ncbi.nlm.nih.gov/pubmed/8437594", "http://www.ncbi.nlm.nih.gov/pubmed/20947659", "http://www.ncbi.nlm.nih.gov/pubmed/16781064", "http://www.ncbi.nlm.nih.gov/pubmed/12412377", "http://www.ncbi.nlm.nih.gov/pubmed/18228687", "http://www.ncbi.nlm.nih.gov/pubmed/1379912", "http://www.ncbi.nlm.nih.gov/pubmed/10155294", "http://www.ncbi.nlm.nih.gov/pubmed/24389070", "http://www.ncbi.nlm.nih.gov/pubmed/24485911", "http://www.ncbi.nlm.nih.gov/pubmed/2023606", "http://www.ncbi.nlm.nih.gov/pubmed/22652185" ]

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[ "Hsp90 inhibition is followed by G1/S cell cycle arrest, downregulation of key signalling proteins such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, and sequestration-mediated inactivation of NF-κB, resulting in disruption of oncogenic signalling integrity, reduced cell proliferation, decline of cell motility, enhanced apoptotic cell death, and finally, sensitization of cancer cells to additional chemotherapy and/or radiotherapy." ]

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[ "Geldanamycin (GA) can be considered a relatively new component with a promising mode of action against human malignancies. It specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone.", "In toto, we have evinced the dose-dependent and cell line-specific actions of geldanamycin on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of critical Hsp90 clients and subsequent disruption of signaling -oncogenic- integrity.", "Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy", "Hsp90 inhibitors at low concentrations, which did not exert cytocidal effects but inactivated key anti-apoptotic proteins including erbB2, Akt, and NF-κB, efficiently sensitized bladder cancer cells (T24, 5637 and UM-UC-3 cells) to in vitro CRT by enhancing apoptosis.", "In mice UM-UC-3 tumor xenografts model, Hsp90 inhibitors successfully potentiated anti-tumor activity of CRT.", "The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro.", "We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-κB, reduced cell proliferation and decline of cell motility.", "In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity.", "Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells", "GA downregulated Met by inhibiting new protein maturation, thereby dampening HGF signaling.", "HGF and chemical hypoxia with CoCl2 cooperatively promoted in vitro invasion and vascular endothelial growth factor (VEGF) secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator and matrix metalloproteinase 2, both of which promote invasion and angiogenesis. Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and HIF-1 pathways.", "Notably, brief GA pretreatment inhibited in vitro invasion and VEGF secretion induced by HGF as effectively as did continuous treatment.", "Moreover, we found that GA inhibited activation of focal adhesion kinase, focal adhesion assembly, and actin reorganization induced by HGF and integrin engagement by extracellular matrix.", "GA widely suppresses extrinsic stimuli-induced signaling that contribute to tumor invasion and angiogenesis in this bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing tumor progression and metastasis.", "upon geldanamycin treatment, bladder cancer cells are prominently arrested in the G1 phase of cell cycle and eventually undergo programmed cell death via combined activation of apoptosis and autophagy.", "geldanamycin administration proved to induce prominent downregulation of several Hsp90 protein clients and downstream effectors, such as membrane receptors (IGF-IR and c-Met), protein kinases (Akt, IKKα, IKKβ and Erk1/2) and transcription factors (FOXOs and NF-κΒ), therefore resulting in the impairment of proliferative -oncogenic- signaling and reduction of cell motility", "17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signalin" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22134243", "http://www.ncbi.nlm.nih.gov/pubmed/20828379", "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "http://www.ncbi.nlm.nih.gov/pubmed/21964864", "http://www.ncbi.nlm.nih.gov/pubmed/17525527" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030336", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030308", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045926", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008285", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043407", "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "Medulloblastoma is the most common malignant cerebellar tumor seen in the pediatric age group, which has a known ability to metastasize extraneurally.", "Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally " ]

[ "Medulloblastoma" ]

[ "Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children", "Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally", "Medulloblastoma (MB) is the most common malignant pediatric brain tumor which is thought to originate from cerebellar granule cell precursors (CGNPs) that fail to properly exit the cell cycle and differentiate.", "Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children.", "Medulloblastoma, the most common pediatric brain tumor, is thought to arise from deregulated proliferation of cerebellar granule precursor (CGP) cells.", "Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is thought to arise from genetic anomalies in developmental pathways required for the normal maturation of the cerebellar cortex, notably developmental pathways for granule cell progenitor (GCP) neurogenesis.", "Most adult brain tumors are supratentorial malignant gliomas, whereas the most common malignant pediatric brain tumor is the cerebellar primitive neuroectodermal tumor (medulloblastoma).", "Mouse models have increased our understanding of the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor that often forms in the cerebellum" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21315459", "http://www.ncbi.nlm.nih.gov/pubmed/23951168", "http://www.ncbi.nlm.nih.gov/pubmed/25499213", "http://www.ncbi.nlm.nih.gov/pubmed/6502196", "http://www.ncbi.nlm.nih.gov/pubmed/21681603", "http://www.ncbi.nlm.nih.gov/pubmed/16479172", "http://www.ncbi.nlm.nih.gov/pubmed/9447621" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:5059", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002528" ]

[ "Carboxyl terminus of hsc70-interacting protein (CHIP) can mediate ubiquitination of the 90 kDa heat-shock protein (hsp90) in vitro, with subsequent proteasomal degradation of the chaperone." ]

[ "Carboxyl terminus of hsc70-interacting protein (CHIP)" ]

[ "C-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation.", "The U-box E3 ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein) binds Hsp90 and/or Hsp70 via its tetratricopeptide repeat (TPR), facilitating ubiquitination of the chaperone-bound client proteins.", "In vitro ubiquitination assays indicated that Ca(2+)/S100A2 and S100P are efficient and specific inhibitors of CHIP-mediated ubiquitination of Hsp70, Hsp90, HSF1, and Smad1.", "The E3 ubiquitin ligase CHIP (C-terminus of Hsc70-interacting protein) is believed to be a central player in the cellular triage decision, as it links the molecular chaperones Hsp70/Hsc70 and Hsp90 to the ubiquitin proteasomal degradation pathway.", "We found that CHIP has a sixfold higher affinity for Hsp90 compared with Hsc70.", "Carboxyl terminus of hsc70-interacting protein (CHIP) can remodel mature aryl hydrocarbon receptor (AhR) complexes and mediate ubiquitination of both the AhR and the 90 kDa heat-shock protein (hsp90) in vitro", "The analysis of the sucrose-gradient-fractionated in vitro translated AhR complexes revealed that CHIP can mediate hsp90 ubiquitination while cooperating with unidentified factors to promote the ubiquitination of mature unliganded AhR complexes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23344957", "http://www.ncbi.nlm.nih.gov/pubmed/17209571", "http://www.ncbi.nlm.nih.gov/pubmed/20618441", "http://www.ncbi.nlm.nih.gov/pubmed/23429937" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000151", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://www.uniprot.org/uniprot/UB2E3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004842", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043743" ]

[ "Phycobiliproteins are derived from the photosynthetic apparatus of cyanobacteria and eukaryotic algae, and form their large extrinsic antenna complexes called phycobilisomes. Phycobilisomes have a core composed from allophycocyanin (APC) and rods, which are of variable phycobiliprotein composition. C-Phycocyanin (C-Pc) is one of the major light harvesting biliprotein pigments constitutively produced by many cyanobacteria, such as Spirulina platenesis (a blue-green alga). B-Phycoerythrin (B-PE) is an other major light-harvesting pigment found in red algae and cyanobacteria. R-phycoerythrin (R-PE) is the major light-harvesting pigment protein of most red algal phycobilisomes." ]

[ "allophycocyanin (APC)", "C-Phycocyanin (C-Pc)", "B-Phycoerythrin (B-PE)", "R-phycoerythrin (R-PE)" ]

[ "An extensive range of pigments including phycobiliproteins are present in algae. C-phycocyanin (C-PC), a phycobiliprotein, is one of the key pigments of Spirulina", "Spirulina platensis produces nutraceutical product C-phycocyanin (C-PC)", "C-Phycocyanin (C-Pc) is one of the major biliprotein pigments of unicellular cyanbacterium of Spirulina platenesis", "Marine Synechococcus owe their specific vivid color (ranging from blue-green to orange) to their large extrinsic antenna complexes called phycobilisomes, comprising a central allophycocyanin core and rods of variable phycobiliprotein composition.", "Three major pigment types can be defined depending on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or phycoerythrin II)", "Phycocyanin--a major phycobiliprotein constitutively produced by many cyanobacteria--", "R-phycoerythrin was isolated and purified from a red alga, Polysiphonia urceolata Grev", "C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga)", "C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties.", "B-Phycoerythrin (B-PE) is a major light-harvesting pigment of microalgae.", "Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria that is widely used as a fluorescent probe and analytical reagent. In this paper, B-phycoerythrin and R-phycocyanin in native state, from the red alga Porphyridium cruentum were obtained by an inexpensive and simple process.", "Phycobiliproteins are derived from the photosynthetic apparatus of cyanobacteria and eukaryotic algae.", "the three major phycobiliprotein types, namely allophycocyanin, phycocyanin, and phycoerythrin", "Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria widely used as a fluorescent probe.", "allophycocyanin (APC)", "R-phycoerythrin is the major light-harvesting pigment protein of most red algal phycobilisomes.", "The purified protein had three absorption peaks at 498, 535, and 565 nm and displayed a fluorescence maximum at 580 nm, which was consistent with the typical spectrum of R-phycoerythrin. The purified R-PE was also identified with electrophoresis.", "Phycobilisomes, the major light-harvesting complexes of cyanobacteria are multimolecular structures made up of chromophoric proteins called phycobiliproteins and non chromophoric linker polypeptides.", "We report here the isolation and nucleotide sequence of the genes, cpeA and cpeB, which in Calothrix PCC 7601 encode the alpha and beta subunits of phycoerythrin, one of the major phycobiliproteins.", "The major light-harvesting complex in eukaryotic red algae and prokaryotic cyanobacteria is the phycobilisome, a water-soluble complex located on the outer surface of the photosynthetic membranes and composed of both pigmented phycobiliproteins (85%) and non-pigmented linker (15%) polypeptides.", "Phycocyanin is a major protein produced by cyanobacteria, but very few phycocyanin-producing strains have been reported.", "In the present work, phycocyanin (PC) and phycoerythrin (PE) from a Nostoc species are proposed as protein markers for electrophoretic techniques.", "Rod structure of a phycoerythrin II-containing phycobilisome. I. Organization and sequence of the gene cluster encoding the major phycobiliprotein rod components in the genome of marine Synechococcus sp. WH8020.", "We now present data showing that the allophycocyanin genes and a second set of phycocyanin genes are transcribed into major mRNAs of 1400 and 1600 bases, respectively", "The amino acid sequences deduced from both rpeA and rpeB present strong homologies with those previously reported for phycoerythrin subunits of cyanobacteria, rhodophyta, and cryptomonads", "These transcripts are present in RNA isolated from cultures grown in red and green light, although lower levels of the 1600-base phycocyanin transcript are present in cells grown in green light", "Phycocyanin is a major protein produced by cyanobacteria, but very few phycocyanin-producing strains have been reported", "The major light-harvesting complex in eukaryotic red algae and prokaryotic cyanobacteria is the phycobilisome, a water-soluble complex located on the outer surface of the photosynthetic membranes and composed of both pigmented phycobiliproteins (85%) and non-pigmented linker (15%) polypeptides", "Phycocyanin--a major phycobiliprotein constitutively produced by many cyanobacteria--holds several promising applications in diagnostics, biomedical research, and therapeutics", "Phycobilisomes, the major light-harvesting complexes of cyanobacteria are multimolecular structures made up of chromophoric proteins called phycobiliproteins and non chromophoric linker polypeptides" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15242812", "http://www.ncbi.nlm.nih.gov/pubmed/18062815", "http://www.ncbi.nlm.nih.gov/pubmed/16569506", "http://www.ncbi.nlm.nih.gov/pubmed/2431391", "http://www.ncbi.nlm.nih.gov/pubmed/1409666", "http://www.ncbi.nlm.nih.gov/pubmed/24063013", "http://www.ncbi.nlm.nih.gov/pubmed/20306699", "http://www.ncbi.nlm.nih.gov/pubmed/12416885", "http://www.ncbi.nlm.nih.gov/pubmed/17234404", "http://www.ncbi.nlm.nih.gov/pubmed/10744320", "http://www.ncbi.nlm.nih.gov/pubmed/6802826", "http://www.ncbi.nlm.nih.gov/pubmed/16592117", "http://www.ncbi.nlm.nih.gov/pubmed/3127591", "http://www.ncbi.nlm.nih.gov/pubmed/18954974", "http://www.ncbi.nlm.nih.gov/pubmed/1903389", "http://www.ncbi.nlm.nih.gov/pubmed/9548282", "http://www.ncbi.nlm.nih.gov/pubmed/11690696", "http://www.ncbi.nlm.nih.gov/pubmed/19224391", "http://www.ncbi.nlm.nih.gov/pubmed/8187585", "http://www.ncbi.nlm.nih.gov/pubmed/16190625", "http://www.ncbi.nlm.nih.gov/pubmed/12767340", "http://www.ncbi.nlm.nih.gov/pubmed/8344905", "http://www.ncbi.nlm.nih.gov/pubmed/23664178", "http://www.ncbi.nlm.nih.gov/pubmed/3931221", "http://www.ncbi.nlm.nih.gov/pubmed/2502578", "http://www.ncbi.nlm.nih.gov/pubmed/24435274", "http://www.ncbi.nlm.nih.gov/pubmed/16593484", "http://www.ncbi.nlm.nih.gov/pubmed/3086870", "http://www.ncbi.nlm.nih.gov/pubmed/7678762", "http://www.ncbi.nlm.nih.gov/pubmed/11504069", "http://www.ncbi.nlm.nih.gov/pubmed/8419325" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000458", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052979" ]

[ "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in the central nervous system.", "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system " ]

[ "yes" ]

[ "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system", "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons", "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay", "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo", "specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels", "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons.", "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.", "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay.", "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2).", "Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD.", "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice.", "This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation.", "PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation.", "Overexpression of only PLK2 increased phosphorylation of aggregated α-syn at S129, which likely is due to increased phosphorylation of soluble α-syn, which then was incorporated into aggregates.", "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons.", "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay.", "Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative (", "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo.", "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system", "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo", "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay", "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice", "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21162130", "http://www.ncbi.nlm.nih.gov/pubmed/21838679", "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "http://www.ncbi.nlm.nih.gov/pubmed/24128992", "http://www.ncbi.nlm.nih.gov/pubmed/23794260", "http://www.ncbi.nlm.nih.gov/pubmed/19004816" ]

[]

[ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.uniprot.org/uniprot/SYUA_ERYPA", "http://www.uniprot.org/uniprot/SYUA_GORGO", "http://www.uniprot.org/uniprot/SYUA_PANPA", "http://www.uniprot.org/uniprot/SYUA_ATEGE", "http://www.uniprot.org/uniprot/SYUA_RAT", "http://www.uniprot.org/uniprot/SYUA_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.uniprot.org/uniprot/PLK2_PONAB", "http://www.uniprot.org/uniprot/SYUA_HUMAN" ]

[ "Traditionally, microsporidia were considered as protozoans, but recently they have been reclassified as the earliest-diverging clade of sequenced fungi. Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites; they are ubiquitous fungi, with genomes that have undergone a strong reduction." ]

[ "Fungi" ]

[ "Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites. Traditionally, these were considered as protozoans but recently have been reclassified as fungi. ", "Microsporidia are ubiquitous fungi with genomes that have undergone a strong reduction", "Microsporidia are unicellular fungi that are obligate endoparasites. ", "Phylogenomics supports microsporidia as the earliest diverging clade of sequenced fungi.", "A combined analysis of thousands of gene trees supports a topology in which microsporidia is a sister group to all other sequenced fungi.", "Altogether, our data strongly support a scenario in which microsporidia is the earliest-diverging clade of sequenced fungi.", "Microsporidia are a large diverse group of intracellular parasites now considered as fungi.", "The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "The kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.", "The preponderance of evidence as to the origin of the microsporidia reveals a close relationship with the fungi, either within the kingdom or as a sister group to it.", "In a subsequent analysis, we excluded the other Microsporidia from the analysis to look for relationships before the divergence of Microsporidia, and found that 43% of the microsporidial genes scored highest with fungal genes, and a higher mean LPI was found with Fungi than with other kingdoms, suggesting that Microsporidia is closely related to Fungi at the genomic level.", "CONCLUSION/SIGNIFICANCE: The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "The kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.", "Microorganisms of the microsporidia group are obligated intracellular protozoa that belong to the phylum Microspora; currently they are considered to be related or belong to the fungi reign" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23917025", "http://www.ncbi.nlm.nih.gov/pubmed/25258042", "http://www.ncbi.nlm.nih.gov/pubmed/22651672", "http://www.ncbi.nlm.nih.gov/pubmed/24104931", "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "http://www.ncbi.nlm.nih.gov/pubmed/24558617", "http://www.ncbi.nlm.nih.gov/pubmed/25182222", "http://www.ncbi.nlm.nih.gov/pubmed/17572334", "http://www.ncbi.nlm.nih.gov/pubmed/23087371", "http://www.ncbi.nlm.nih.gov/pubmed/10666703", "http://www.ncbi.nlm.nih.gov/pubmed/17051209", "http://www.ncbi.nlm.nih.gov/pubmed/22503551", "http://www.ncbi.nlm.nih.gov/pubmed/25134955", "http://www.ncbi.nlm.nih.gov/pubmed/18976912" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002965", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016814", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021861" ]

[ "The inheritance pattern of Emery-Dreifuss muscular dystrophy (EDMD) can be X-linked, autosomal dominant or autosomal recessive." ]

[ "X-linked", "autosomal dominant", "autosomal recessive" ]

[ ". Loss-of-function truncation mutations in EMD, encoding the nuclear membrane protein emerin, cause X-linked Emery-Dreifuss muscular dystrophy (EDMD) characterized by localized contractures and skeletal myopathy in adolescence, sinus node dysfunction (SND) in early adulthood, and atrial fibrillation as a variably associated trait.", "Mutation of EMD can underlie X-linked familial AF. Lys37del is associated with epithelial cell emerin deficiency, as in EDMD, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease. Targeted genetic testing of EMD should be considered in patients with SND-associated AF and/or family history suggesting X-linked inheritance.", "The Emery-Dreifuss muscular dystrophy is a form of muscular dystrophy that frequently presents early contractures and cardiac conduction defects, caused by emerin deficiency in the inner nuclear membrane of the muscular fibers.", "compatible with X-linked inheritance form", "The first patient was a member of a family with molecularly proven X-linked EDMD.", "As these resemble the cardiac features of patients with the autosomal dominant variant of EDMD, we examined the lamin A/C gene, identifying a de-novo mutation in the propositus.", "contribute to disease severity in autosomal dominant EDMD.", "The STA gene encodes emerin and is one of the genes that is affected in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that EDMD caused by the STA gene mutation is associated with X-linked recessive inheritance, the genotype-phenotype correlations, with special reference to cardiac manifestations, are not well defined.", "Emery-Dreifuss muscular dystrophy (EDMD) is a muscular disorder characterized by 1) early contracture of the elbows. Achilles tendons and post-cervical muscles, 2) slowly progressive muscle wasting and weakness with a humeroperoneal distribution, and 3) life-threatening cardiomyopathy with conduction block. Most of families with EDMD show X-linked recessive inheritance with mutations in the STA gene on chromosome Xq28, which encodes a protein named emerin. A rare autosomal dominant form of EDMD (AD-EDMD) is caused by mutations in lamin A/C gene (LMNA) on chromosome 1q21. Both emerin and lamin A/C are located in the inner surface membrane of the nucleus.", "Emery-Dreifuss muscular dystrophy is an X-linked recessive myopathy. The patient had no familial background of the disease. This patient might have a sporadic inheritance pattern with severe cardiac involvement.", "autosomal dominant Emery-Dreifuss muscular dystrophy,", "Emery-Dreifuss muscular dystrophy is characterized by the clinical triad of early onset contractures of elbows, Achilles tendons and spine, wasting and weakness with a predominantly humero-peroneal distribution and life-threatening cardiac conduction defects and/or cardiomyopathy. Two main types of inheritance have been described: the X-linked form is caused by mutations in the STA gene on locus Xq28 and the gene for the autosomal dominant form (LMNA gene) has been localized on chromosome 1q11-q23. Recently, mutations in this LMNA gene have been also found to be responsible for the less frequent autosomal recessive form of the disease.", "Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form.", "including X-linked Emery-Dreifuss MD,", "this form is not X-linked Emery-Dreifuss MD. We suggest that these patients represent a severe MD characterized by early onset distal wasting and severe rigidity of the spine, with probable autosomal recessive inheritance.", "Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation.", "One family presented a rare autosomal dominant variant of Emery-Dreifuss muscular dystrophy, another with X-linked recessive inheritance showed unusual intrafamilial variability.", "Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant.", "Tendon contractures may be a partial expression of this myopathic disorder, suggesting an autosomal dominant inheritance with variable penetrance. A muscular dystrophy clinically similar to that of the Emery-Dreifuss (EDMD) type can thus occur in women.", "Since the disease was diagnosed in 3 brothers, the X-coupled recessive type of its inheritance is assumed. An opinion is advanced that the described form is a clinical variety of Emery-Dreyfus myodystrophy.", "Emery-Dreifuss syndrome (EDS)", "the term Emery-Dreifuss muscular dystrophy should be avoided. Instead, each case of EDS should be classified as myopathic or neurogenic with X chromosome recessive or autosomal dominant inheritance.", "Emery-Dreifuss muscular dystrophy is a syndrome with five salient features: early and unusual contractures; humeroperoneal muscle wasting; the slow progression of weakness, beginning in childhood; cardiac conduction defects; and X-linked inheritance. We present two cases and detail other reports with a similar constellation of findings with apparent autosomal dominant inheritance.", "Emery-Dreifuss muscular dystrophy with proximal weakness in both the upper and lower limbs and X-linked scapuloperoneal muscular dystrophy represent the same disorder.", "There is at least one other report of autosomal dominant transmission of this clinical picture, which had previously only been reported as Emery-Dreifuss muscular dystrophy with X-linked recessive inheritance." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9536090", "http://www.ncbi.nlm.nih.gov/pubmed/8445613", "http://www.ncbi.nlm.nih.gov/pubmed/11799477", "http://www.ncbi.nlm.nih.gov/pubmed/11863303", "http://www.ncbi.nlm.nih.gov/pubmed/23349612", "http://www.ncbi.nlm.nih.gov/pubmed/8042665", "http://www.ncbi.nlm.nih.gov/pubmed/10080180", "http://www.ncbi.nlm.nih.gov/pubmed/16791377", "http://www.ncbi.nlm.nih.gov/pubmed/3729752", "http://www.ncbi.nlm.nih.gov/pubmed/4022362", "http://www.ncbi.nlm.nih.gov/pubmed/3203701", "http://www.ncbi.nlm.nih.gov/pubmed/3701378", "http://www.ncbi.nlm.nih.gov/pubmed/12424964", "http://www.ncbi.nlm.nih.gov/pubmed/16585054", "http://www.ncbi.nlm.nih.gov/pubmed/11731280", "http://www.ncbi.nlm.nih.gov/pubmed/9781539", "http://www.ncbi.nlm.nih.gov/pubmed/2230849", "http://www.ncbi.nlm.nih.gov/pubmed/2163170", "http://www.ncbi.nlm.nih.gov/pubmed/18266676", "http://www.ncbi.nlm.nih.gov/pubmed/15967842" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020389", "http://www.disease-ontology.org/api/metadata/DOID:655", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050172", "http://www.disease-ontology.org/api/metadata/DOID:11726" ]

[ "Dabigatran is orally administered, reverisble direct and competetive inhibitor of both free and bouded thrombin." ]

[]

[ "Dabigatran etexilate is a novel oral direct thrombin inhibitor, which provides stroke risk reduction for patients with nonvalvular atrial fibrillation. ", "Dabigatran is a potent reversible, competitive direct thrombin inhibitor which is available as the prodrug, Dabigatran etexilate.", "The recently introduced oral direct thrombin antagonist, dabigatran, has been shown in phase III clinical trials to be noninferior in efficacy to warfarin for the prevention of thromboembolic events in patients with atrial fibrillation, as well as in treatment of acute venous thromboembolism.", "Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. ", "Dabigatran etexilate is a direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin.", "Direct inhibitors of FXa (rivaroxaban), FVIIa (BMS-593214), thrombin (dabigatran, argatroban) and FXIa (BMS-262084) were included for comparison. ", "Two agents, the direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitor rivaroxaban, have recently been approved in the EU and several other countries for the prevention of VTE after total hip or knee replacement surgery. ", "The direct thrombin inhibitor dabigatran is farthest along in development.", "Lastly, inhibitors of thrombin activity are composed of either indirect (UFH, LMWH), or direct thrombin (FIIa) inhibitors including: hirudin, argatroban, melagatran, ximelagatran, dabigatran, and bivalirudin.", "The effect of the oral direct activated factor X (factor Xa) inhibitor apixaban on tissue factor-induced thrombin generation in human plasma was investigated in vitro using the calibrated automated thrombogram (CAT) method and compared with the oral direct factor Xa inhibitor rivaroxaban and the direct thrombin inhibitor dabigatran.", "The DTI dabigatran etexilate was recently shown to provide superior risk reduction to warfarin for stroke and systemic embolism for patients with nonvalvular AF and recently gained US Food and Drug Administration approval for this indication." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20589316", "http://www.ncbi.nlm.nih.gov/pubmed/22388002", "http://www.ncbi.nlm.nih.gov/pubmed/22480286", "http://www.ncbi.nlm.nih.gov/pubmed/21666370", "http://www.ncbi.nlm.nih.gov/pubmed/23466964", "http://www.ncbi.nlm.nih.gov/pubmed/23031622", "http://www.ncbi.nlm.nih.gov/pubmed/19888525", "http://www.ncbi.nlm.nih.gov/pubmed/16637459", "http://www.ncbi.nlm.nih.gov/pubmed/18425569", "http://www.ncbi.nlm.nih.gov/pubmed/21988948", "http://www.ncbi.nlm.nih.gov/pubmed/21526168", "http://www.ncbi.nlm.nih.gov/pubmed/20888031" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.biosemantics.org/jochem#4242811" ]

[ "Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease." ]

[ "Batten disease", "juvenile-onset neuronal ceroid lipofuscinosis", "JNCL" ]

[ "Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. ", "human CLN3 that is defective in Batten disease, localizes to the vacuole", "JNCL results from mutations in CLN3 on chromosome 16p12.1.", "Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease.", "Batten disease [juvenile-onset neuronal ceroid lipofuscinosis (JNCL)], the most common progressive encephalopathy of childhood, is caused by mutations in a novel lysosomal membrane protein (CLN3) with unknown function.", "the human CLN3 gene that is defective in Batten disease,", "ln3 was recently identified as the gene defective in juvenile Batten disease, an inherited neurodegenerative disease of childhood", "Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disorder of childhood, is caused by mutations in a recently identified gene ( CLN3 ) localized to chromosome 16p11.2-12.1. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10332042", "http://www.ncbi.nlm.nih.gov/pubmed/16251196", "http://www.ncbi.nlm.nih.gov/pubmed/17868323", "http://www.ncbi.nlm.nih.gov/pubmed/16423829", "http://www.ncbi.nlm.nih.gov/pubmed/10384264", "http://www.ncbi.nlm.nih.gov/pubmed/16515873", "http://www.ncbi.nlm.nih.gov/pubmed/15471887", "http://www.ncbi.nlm.nih.gov/pubmed/9384607", "http://www.ncbi.nlm.nih.gov/pubmed/10509355" ]

[ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_5136313132340012" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5136313132340012", "o": "Cln3" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_51363131323400D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363131323400D", "o": "Battenin" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363131323400E", "o": "Protein CLN3" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_51363131323400E" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131008" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513239363131006", "o": "Battenin" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513239363131007", "o": "Protein CLN3" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131007" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131006" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513239363131008", "o": "CLN3" } ]

[ "http://www.uniprot.org/uniprot/CLN3_MOUSE", "http://www.uniprot.org/uniprot/CLN3_MACFA", "http://www.uniprot.org/uniprot/CLN3_HUMAN", "http://www.uniprot.org/uniprot/CG13_YEAST", "http://www.uniprot.org/uniprot/CLN3_DICDI", "http://www.uniprot.org/uniprot/CLN3_CANFA" ]

[ "ARB1, ARB2, TAK1, p38, TRalpha1" ]

[ "ARB1", "ARB2", "TAK1", "p38", "TRalpha1" ]

[ "n FM the reduced mRNA expression of ARB1 (p<0.05, -37%) and ARB2 (p<0.05, -42%) was associated with a reduction of the messenger for TRalpha1 (p<0.05, -85%) and TRalpha2 (p<0.05, -73%).", "hese data reveal that in human heart failure the reduction of beta-adrenergic receptors is associated with reduced expression of both TRalpha1 and TRalpha2 isoforms of thyroid hormone receptors.", "Mitigating TRalpha1 effects, both TRalpha2 and TRbeta1 attenuate TRalpha1-induced myocardial growth and gene expression by diminishing TAK1 and p38 activities, respectively.", "Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1.", "These data reveal that in human heart failure the reduction of beta-adrenergic receptors is associated with reduced expression of both TRalpha1 and TRalpha2 isoforms of thyroid hormone receptors." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11731613", "http://www.ncbi.nlm.nih.gov/pubmed/18031713", "http://www.ncbi.nlm.nih.gov/pubmed/15831522" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I ", "In an experimental setting, baseline protein synthesis rates in connective tissue appeared normal in classic Ehlers-Danlos syndrome patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections." ]

[ "yes" ]

[ "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I", "IGF-I injections significantly increased FSR values in cEDS patients but not in controls", "In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections", "In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections", "IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25103963" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:13359", "http://www.uniprot.org/uniprot/IGF_MYXGL", "http://www.uniprot.org/uniprot/IGF1_CAPHI" ]

[ "HMMpTM, MetaTM, Philius, HMM_RA, HMMTOP, MEMSAT3, HMM-TM, TMHMM, Phobius and SignalP." ]

[ "HMMpTM", "MetaTM", "Philius", "HMM_RA", "HMMTOP", "MEMSAT3", "HMM-TM", "TMHMM", "Phobius", "SignalP" ]

[ "HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction", "We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. The method is freely available at http://bioinformatics.biol.uoa.gr/HMMpTM", "MetaTM - a consensus method for transmembrane protein topology prediction.", "A novel TM consensus method, named MetaTM, is proposed in this work. MetaTM is based on support vector machine models and combines the results of six TM topology predictors and two signal peptide predictors. On a large data set comprising 1460 sequences of TM proteins with known topologies and 2362 globular protein sequences it correctly predicts 86.7% of all topologies. CONCLUSION: Combining several TM predictors in a consensus prediction framework improves overall accuracy compared to any of the individual methods. Our proposed SVM-based system also has higher accuracy than a previous consensus predictor. MetaTM is made available both as downloadable source code and as DAS server at http://MetaTM.sbc.su.se", "We present a support vector machine-based (SVM) TM protein topology predictor that integrates both signal peptide and re-entrant helix prediction, benchmarked with full cross-validation on a novel data set of 131 sequences with known crystal structures. The method achieves topology prediction accuracy of 89%, while signal peptides and re-entrant helices are predicted with 93% and 44% accuracy respectively. An additional SVM trained to discriminate between globular and TM proteins detected zero false positives, with a low false negative rate of 0.4%. We present the results of applying these tools to a number of complete genomes. Source code, data sets and a web server are freely available from http://bioinf.cs.ucl.ac.uk/psipred/", "Hidden Markov models (HMMs) have been successfully applied to the tasks of transmembrane protein topology prediction and signal peptide prediction. In this paper we expand upon this work by making use of the more powerful class of dynamic Bayesian networks (DBNs). Our model, Philius, is inspired by a previously published HMM, Phobius, and combines a signal peptide submodel with a transmembrane submodel. We introduce a two-stage DBN decoder that combines the power of posterior decoding with the grammar constraints of Viterbi-style decoding. Philius also provides protein type, segment, and topology confidence metrics to aid in the interpretation of the predictions", "We report a relative improvement of 13% over Phobius in full-topology prediction accuracy on transmembrane proteins, and a sensitivity and specificity of 0.96 in detecting signal peptides", "HMM_RA: an improved method for alpha-helical transmembrane protein topology prediction", "This paper presents a Hidden Markov Model (referred to as HMM_RA) that can predict the topology of alpha-helical transmembrane proteins with improved performance. HMM_RA adopts the same structure as the HMMTOP method, which has five modules: inside loop, inside helix tail, membrane helix, outside helix tail and outside loop. Each module consists of one or multiple states", "A new method (MEMSAT3) for predicting transmembrane protein topology from sequence profiles is described and benchmarked with full cross-validation on a standard data set of 184 transmembrane proteins", "The algorithms presented here, are easily implemented in any kind of a Hidden Markov Model, whereas the prediction method (HMM-TM) is freely available for academic users", "TMHMM, the current state-of-the-art method, has less than 52% accuracy in topology prediction on one set of transmembrane proteins of known topology. Based on the observation that there are functional domains that occur preferentially internal or external to the membrane, we have extended the model of TMHMM to incorporate functional domains, using a probabilistic approach originally developed for computational gene finding. Our extension is better than TMHMM in predicting the topology of transmembrane proteins. As prediction of functional domain improves, our system's prediction accuracy will likely improve as well", "Here, we present Phobius, a combined transmembrane protein topology and signal peptide predictor. The predictor is based on a hidden Markov model (HMM) that models the different sequence regions of a signal peptide and the different regions of a transmembrane protein in a series of interconnected states. Training was done on a newly assembled and curated dataset. Compared to TMHMM and SignalP, errors coming from cross-prediction between transmembrane segments and signal peptides were reduced substantially by Phobius. False classifications of signal peptides were reduced from 26.1% to 3.9% and false classifications of transmembrane helices were reduced from 19.0% to 7.7%. Phobius was applied to the proteomes of Homo sapiens and Escherichia coli. Here we also noted a drastic reduction of false classifications compared to TMHMM/SignalP, suggesting that Phobius is well suited for whole-genome annotation of signal peptides and transmembrane regions", "HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction.", "The HMMTOP transmembrane topology prediction server." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19470175", "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "http://www.ncbi.nlm.nih.gov/pubmed/19812766", "http://www.ncbi.nlm.nih.gov/pubmed/16568545", "http://www.ncbi.nlm.nih.gov/pubmed/24225132", "http://www.ncbi.nlm.nih.gov/pubmed/11590105", "http://www.ncbi.nlm.nih.gov/pubmed/17237066", "http://www.ncbi.nlm.nih.gov/pubmed/16597327", "http://www.ncbi.nlm.nih.gov/pubmed/19785723", "http://www.ncbi.nlm.nih.gov/pubmed/15111065" ]

[]

[]

[ "Isochores are relatively long regions with a relatively homogeneous GC content, and with rather sharp boundaries with neighboring isochores. The base composition, and thus the GC content may differ between different isochores, but is more or less consistent within a given isochore." ]

[ "no" ]

[ "The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes.", "Isochores are large regions of relatively homogeneous nucleotide composition", "Vertebrate genomes are comprised of isochores that are relatively long (>100 kb) regions with a relatively homogenous (either GC-rich or AT-rich) base composition and with rather sharp boundaries with neighboring isochores.", "The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores", "Isochores, i.e. stretches of DNA with a distinct sequence composition and thus a specific GC content", "The human genome is composed of long stretches of DNA with distinct GC contents, called isochores or GC-content domains.", "The human genome is divided into isochores, large stretches (>>300 kb) of genomic DNA with more or less consistent GC content. ", "Many eukaryotic genomes contain isochore regions, mosaics of homogeneous GC content that can abruptly change from one neighboring isochore to the next.", "One of the most striking features of mammalian and birds chromosomes is the variation in the guanine-cytosine (GC) content that occurs over scales of hundreds of kilobases to megabases; this is known as the \"isochore\" structure.", "The segmentation analysis shows that there are stronger indications of GC content changes at isochore borders than within an isochore.", "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them.", "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them.", "An isochore sequence may pass a homogeneity test when GC content fluctuations at smaller length scales are ignored or averaged out.", "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18092827", "http://www.ncbi.nlm.nih.gov/pubmed/17317955", "http://www.ncbi.nlm.nih.gov/pubmed/22934101", "http://www.ncbi.nlm.nih.gov/pubmed/15978039", "http://www.ncbi.nlm.nih.gov/pubmed/19443854", "http://www.ncbi.nlm.nih.gov/pubmed/11591467", "http://www.ncbi.nlm.nih.gov/pubmed/14962664", "http://www.ncbi.nlm.nih.gov/pubmed/17674077", "http://www.ncbi.nlm.nih.gov/pubmed/21669806", "http://www.ncbi.nlm.nih.gov/pubmed/12468094", "http://www.ncbi.nlm.nih.gov/pubmed/16623701", "http://www.ncbi.nlm.nih.gov/pubmed/11319260", "http://www.ncbi.nlm.nih.gov/pubmed/17389148", "http://www.ncbi.nlm.nih.gov/pubmed/17057231", "http://www.ncbi.nlm.nih.gov/pubmed/9254920", "http://www.ncbi.nlm.nih.gov/pubmed/20948965", "http://www.ncbi.nlm.nih.gov/pubmed/21795750" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001482", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032085" ]

[ "Yes, induction of alpha-tubulin acetylation correlates with inhibition of cell motility, while it is involved in additional cellular processes, e.g. cell cycle progression, differentiation, intracellular trafficking, and signalling. Dynamic microtubule (MT) acetylation/deacetylation mediating cell motility and adhesion is controlled by enzymes such as HDAC6, a major cytoplasmic α-tubulin deacetylase. While its overexpression and activation is capable to enhance cell motility, HDAC6 activity can also be negatively regulated by a number of cellular inhibitors, thus decreasing the ability of cells for migration." ]

[ "yes" ]

[ "In this study, we found that paclitaxel induced tubulin acetylation in endothelial and tumor cells, at concentrations that affected cell motility but not proliferation (10(-8) to 10(-9) M, for 4 hours). Induction of tubulin acetylation correlated with inhibition of motility but not proliferation based on a comparison of highly and poorly cytotoxic taxanes (paclitaxel and IDN5390) and tumor cell lines sensitive and resistant to paclitaxel (1A9 and 1A9 PTX22).", "we found that overexpression of the tubulin deacetylase SIRT2 increased cell motility and reduced cell response to the anti-motility activity of paclitaxel. Conversely, the SIRT2 inhibitor splitomicin reduced cell motility and potentiated the anti-motility activity of paclitaxel. The inhibitory effect was further potentiated by the addition of the HDAC6 inhibitor trichostatin A.", "Cell motility and adhesion involves dynamic microtubule (MT) acetylation/deacetylation, a process regulated by enzymes as HDAC6, a major cytoplasmic α-tubulin deacetylase.", "GRK2 and HDAC6 colocalize in the lamellipodia of migrating cells, leading to local tubulin deacetylation and enhanced motility.", "This review highlights the emerging roles of tubulin acetylation in multiple cellular functions, ranging from cell motility, cell cycle progression or cell differentiation to intracellular trafficking and signalling.", "Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6.", "Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments.", "\"tubacin,\" which inhibits alpha-tubulin deacetylation in mammalian cells.", "We provide evidence that class II histone deacetylase 6 (HDAC6) is the intracellular target of tubacin.", "Tubacin treatment did not affect the stability of microtubules but did decrease cell motility.", "They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents.", "Furthermore, overexpression of HDAC6 promotes chemotactic cell movement, supporting the idea that HDAC6-mediated deacetylation regulates microtubule-dependent cell motility.", "HDAC6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 dynamically and directly associates with and phosphorylates HDAC6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22193721", "http://www.ncbi.nlm.nih.gov/pubmed/20308065", "http://www.ncbi.nlm.nih.gov/pubmed/23019416", "http://www.ncbi.nlm.nih.gov/pubmed/12024216", "http://www.ncbi.nlm.nih.gov/pubmed/22589388", "http://www.ncbi.nlm.nih.gov/pubmed/20940043", "http://www.ncbi.nlm.nih.gov/pubmed/12677000" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054443", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007021", "http://www.uniprot.org/uniprot/TBA_GIBZE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002465", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000145", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014404", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019799", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090043", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071929", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000107", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045298" ]

[ "Flybow and Drosophila Brainbow." ]

[ "Flybow", "Drosophila Brainbow" ]

[ "Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster.", "To facilitate studies of neural network architecture and formation, we generated three Drosophila melanogaster variants of the mouse Brainbow-2 system, called Flybow. Sequences encoding different membrane-tethered fluorescent proteins were arranged in pairs within cassettes flanked by recombination sites. Flybow combines the Gal4-upstream activating sequence binary system to regulate transgene expression and an inducible modified Flp-FRT system to drive inversions and excisions of cassettes. This provides spatial and temporal control over the stochastic expression of one of two or four reporters within one sample. Using the visual system, the embryonic nervous system and the wing imaginal disc, we show that Flybow in conjunction with specific Gal4 drivers can be used to visualize cell morphology with high resolution. Finally, we demonstrate that this labeling approach is compatible with available Flp-FRT-based techniques, such as mosaic analysis with a repressible cell marker; this could further support the genetic analysis of neural circuit assembly and function.", "Drosophila Brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns.", "We developed a multicolor neuron labeling technique in Drosophila melanogaster that combines the power to specifically target different neural populations with the label diversity provided by stochastic color choice. This adaptation of vertebrate Brainbow uses recombination to select one of three epitope-tagged proteins detectable by immunofluorescence. Two copies of this construct yield six bright, separable colors. We used Drosophila Brainbow to study the innervation patterns of multiple antennal lobe projection neuron lineages in the same preparation and to observe the relative trajectories of individual aminergic neurons. Nerve bundles, and even individual neurites hundreds of micrometers long, can be followed with definitive color labeling. We traced motor neurons in the subesophageal ganglion and correlated them to neuromuscular junctions to identify their specific proboscis muscle targets. The ability to independently visualize multiple lineage or neuron projections in the same preparation greatly advances the goal of mapping how neurons connect into circuits.", "Brainbow: new resources and emerging biological applications for multicolor genetic labeling and analysis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25657347", "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "http://www.ncbi.nlm.nih.gov/pubmed/21297619" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004331", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007553" ]

[ "EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from the cellular cortex. A number of growth factors have been shown to be involved in this process. These include fibroblast growth factors (FGFs), TGF-β1, TGF-β2, TNF-α, CCN family, Sonic Hedgehog (SHh), Notch1, GF-β, Wnt, EGF, bFGF, IGF-I and IGF-II." ]

[ "fibroblast growth factors (FGFs)", "TGF-β1", "TGF-β2", "TNF-α", "CCN family", "Sonic Hedgehog (SHh)", "Notch1", "GF-β", "Wnt", "EGF", "bFGF", "IGF-I", "IGF-II" ]

[ "Moreover, recent studies have shown that most EMT cases are regulated by soluble growth factors or cytokines. Among these factors, fibroblast growth factors (FGFs) execute diverse functions by binding to and activating members of the FGF receptor (FGFR) family, including FGFR1-4.", "Fibroblast growth factor receptor 1 is an oncoprotein that is involved in tumorigenesis, and PD173074 is known to be a selective inhibitor of FGFR1.", "Fibroblast growth factor receptor 1 was also overexpressed in EMT cell lines compared with non-EMT cell lines.", "Furthermore, treatment of HOC313 cells with PD173074 suppressed cellular proliferation and invasion and reduced ERK1/2 and p38 activation.", "In addition, the expression levels of certain matrix metalloproteinases (MMPs), whose genes contain activator protein-1 (AP-1) promoter sites, as well as Snail1 and Snail2 were reduced following PD173074 treatment.", "Taken together, these data suggest that PD173074 inhibits the MAPK pathway, which regulates the activity of AP-1 and induces MET.", "egulation of Na,K-ATPase β1-subunit in TGF-β2-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells", "The EMT process is mediated via exposure to vitreous cytokines and growth factors such as TGF-β2.", "Previous studies have shown that Na,K-ATPase is required for maintaining a normal polarized epithelial phenotype and that decreased Na,K-ATPase function and subunit levels are associated with TGF-β1-mediated EMT in kidney cells.", "loss of Na,K-ATPase β1 is a potential contributor to TGF-β2-mediated EMT in RPE cells.", "MT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-β elicited EMT in Smad-dependent manner and TNF-α accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion.", "Comprehensive expression analysis unraveled genes differentially regulated by TGF-β and TNF-α, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. ", "Our recent studies found that CCN1 plays a critical role in pancreatic carcinogenesis through the induction of EMT and stemness.", "Here we show that CCN1 regulates the Sonic Hedgehog (SHh) signaling pathway, which is associated with the PDAC progression and poor prognosis.", "SHh regulation by CCN1 in pancreatic cancer cells is mediated through the active Notch-1.", "These extensive studies propose that targeting CCN1 can provide a new treatment option for patients with pancreatic cancer since blocking CCN1 simultaneously blocks two critical pathways (i.e. SHh and Notch1) associated with the development of the disease as well as drug resistance.", "GF-β-induced epithelial-mesenchymal transition", "The cytokine TGF-β, which is expressed by tumor-infiltrating immune cells, stands out as a master regulator of the pro-invasive tumor microenvironment. TGF-β cooperates with stem cell pathways, such as Wnt and Ras signaling, to induce EMT. In addition, TGF-β contributes to an EMT-permissive microenvironment by switching the phenotypes of tumor-infiltrating immune cells, which thereby mount pro-invasive and pro-metastatic immune responses.", "In this review, we discuss the role of TGF-β-induced EMT as a link between cancer and inflammation in the context of questions, which from our point of view are key to answer in order to understand the functionality of EMT in tumors.", "ranscription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition", "Treatment of HT29 and DLD-1 cells with EGF and/or basic FGF (bFGF) induced EMT and significantly increased sLe(x/a) expression resulting in enhanced E-selectin binding activity.", "Upon hypoxia, TGFβ addition or EGFRvIII expression, MCF7, A549 and NMuMG epithelial cells acquired a spindle shape and lost cell-cell contacts. Expression of epithelial markers such as E-cadherin decreased, whereas mesenchymal markers such as vimentin and N-cadherin increased.", "The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-beta, whose activities are dysregulated during malignant tumor progression.", "Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis.", "nflammatory cytokines augments TGF-beta1-induced epithelial-mesenchymal transition in A549 cells by up-regulating TbetaR-I", "In this study, we report that cytomix (a mixture of IL-1beta, TNF-alpha and IFN-gamma) significantly enhances TGF-beta1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin.", "IL-1beta or TNF-alpha alone can also augment TGF-beta1-induced EMT. However, a combination of IL-1beta and TNF-alpha or the cytomix is more potent to induce EMT.", "These results indicate that inflammatory cytokines together with TGF-beta1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.", "TGF-beta stimulated epithelial to mesenchyme transdifferentiation (EMT) in the presence of TGF-alpha, as characterized by increased expression of fibronectin and changes in TGF-beta receptor binding.", "EMT is typically induced by transforming growth factor-beta1 (TGF-beta1) and inhibited by hepatocyte growth factor (HGF).", "Exposure of MDCK cells to 10 ng/ml TGF-beta1 for 72 h induced EMT as evidenced by conversion to the spindle-like morphology, loss of E-cadherin, and activation of alpha-smooth muscle actin.", "In contrast, Akt1 down-regulation in IGF-IR-stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial-mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. The phenotypic effects of Akt1 down-regulation were accompanied by enhanced extracellular signal-related kinase (ERK) activation, which contributed to the induction of migration and EMT.", "ransforming growth factors beta (TGF-betas) inhibit growth of epithelial cells and induce differentiation changes, such as epithelial-mesenchymal transition (EMT).", "Ha-Ras cooperates with transforming growth factor beta (TGFbeta) to cause epithelial mesenchymal transition (EMT) characterized by spindle-like cell morphology, loss of epithelial markers, and induction of mesenchymal markers.", "IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition", "We can show that (1) IGF-II induces a rapid epithelium to mesenchymal transition;", "Based on the given case of IGF-II and E-cadherin/beta-catenin complex, this study reveals the backbone of a cascade connecting growth factor signaling with cell-cell adhesion during EMT.", "The NBT-II rat carcinoma cell line exhibits two mutually exclusive responses to FGF-1 and EGF, entering mitosis at cell confluency while undergoing an epithelium-to-mesenchyme transition (EMT) when cultured at subconfluency.", "EMT requires continuous TGFbeta receptor (TGFbeta-R) and oncogenic Ras signaling and is stabilized by autocrine TGFbeta production", "EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFbeta-R and Raf/MAPK signaling" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "http://www.ncbi.nlm.nih.gov/pubmed/23437179", "http://www.ncbi.nlm.nih.gov/pubmed/17720949", "http://www.ncbi.nlm.nih.gov/pubmed/22547830", "http://www.ncbi.nlm.nih.gov/pubmed/16365168", "http://www.ncbi.nlm.nih.gov/pubmed/21680037", "http://www.ncbi.nlm.nih.gov/pubmed/15121845", "http://www.ncbi.nlm.nih.gov/pubmed/11790801", "http://www.ncbi.nlm.nih.gov/pubmed/22627188", "http://www.ncbi.nlm.nih.gov/pubmed/11526479", "http://www.ncbi.nlm.nih.gov/pubmed/16868306", "http://www.ncbi.nlm.nih.gov/pubmed/7593195", "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "http://www.ncbi.nlm.nih.gov/pubmed/20531305", "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "http://www.ncbi.nlm.nih.gov/pubmed/20075196" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070848", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005346", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019838", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017978", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008083", "http://www.biosemantics.org/jochem#4249315", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036341" ]

[ "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions. Aft1 interacts with the FOB (ferrioxamine B) transporter Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment. Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability. Aft1 has also been shown to affect a diverse range of cellular processes, including the RIM101 pH pathway, cell-wall stability, DNA damage, protein transport, chromosome stability, mitochondrial function, while it was recently shown to interact with the kinetochore protein Iml3 and to promote pericentromeric cohesin." ]

[]

[ "Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake", "AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.", "Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast", "Iron deprivation of Saccharomyces cerevisiae induces transcription of genes required for high-affinity iron uptake. AFT1 mediates this transcriptional control.", "The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae.", "Aft1 displays phosphorylation modifications depending on the growth stage of the cells, and it might link induction of genes for iron uptake to other metabolically dominant requirement for cell growth.", "an aft1 mutation in S. cerevisiae that makes cells dependent on iron for growth", "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae.", "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions", "the nuclear export of Aft1 is critical for ensuring iron-responsive transcriptional activation of the Aft1 regulon and that the nuclear import/export systems are involved in iron sensing by Aft1 in S. cerevisiae.", "the Aft1 iron-responsive DNA-binding factor", "Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae.", "iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins", "The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion,", "the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog", "The transcription factors Aft1 and Aft2 from Saccharomyces cerevisiae regulate the expression of genes involved in iron homeostasis.", "iron insufficiency-responsive transcription factor Aft1", "The mRNA levels of 14 proteins involved in iron homeostasis were shown to be increased by cisplatin. Interestingly, the expression of all 14 genes is known to be regulated by Aft1, a transcription factor activated in response to iron insufficiency", "Aft1 is a transcriptional activator in Saccharomyces cerevisiae that responds to iron availability and regulates the expression of genes in the iron regulon", "we found that Aft1 physically interacts with the FOB (ferrioxamine B) transporter Arn3", "These results suggest that Aft1 interacts with Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment", "The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low-iron conditions", "Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability", "We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in DNA damage repair is mediated by iron. In contrast, through both directed studies and microarray transcriptional profiling, we show that the role of Aft1 in chromosome maintenance and benomyl resistance is independent of its iron regulatory role, potentially through a nontranscriptional mechanism.", "Aft1p is a major iron regulator in budding yeast Saccharomyces cerevisiae. It indirectly senses cytosolic Fe status and responds by activating or repressing iron regulon genes", "Expression of components of the high-affinity system is controlled by the Aft1 transcriptional factor", "Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin", "The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a well established role in regulating iron homeostasis through the transcriptional induction of iron-regulon genes", "recent studies have implicated Aft1 in other cellular processes independent of iron regulation such as chromosome stability", "Aft1 interacts with and co-localizes with kinetochore proteins", "Our work defines a new role for Aft1 in chromosome stability and transmission.", "Our genetic network reveals that Aft1 affects a diverse range of cellular processes, including the RIM101 pH pathway, cell-wall stability, DNA damage, protein transport, chromosome stability, and mitochondrial function." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8670839", "http://www.ncbi.nlm.nih.gov/pubmed/11877447", "http://www.ncbi.nlm.nih.gov/pubmed/16024809", "http://www.ncbi.nlm.nih.gov/pubmed/21542867", "http://www.ncbi.nlm.nih.gov/pubmed/17096368", "http://www.ncbi.nlm.nih.gov/pubmed/14739928", "http://www.ncbi.nlm.nih.gov/pubmed/15649888", "http://www.ncbi.nlm.nih.gov/pubmed/16648636", "http://www.ncbi.nlm.nih.gov/pubmed/9200812", "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "http://www.ncbi.nlm.nih.gov/pubmed/19469713", "http://www.ncbi.nlm.nih.gov/pubmed/11223939", "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "http://www.ncbi.nlm.nih.gov/pubmed/21361388", "http://www.ncbi.nlm.nih.gov/pubmed/7720713" ]

[]

[ "http://www.uniprot.org/uniprot/AFT1_YEAST" ]

[ "Yes, PLN mutations can lead to dilated cardiomyopathy." ]

[ "yes" ]

[ "A PLN founder mutation (43 cases) and LMNA mutations (19 cases, 16 different mutations) were most prevalent and often demonstrated a specific phenotype.", "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", "Arg(9) → Cys (R9C) and Arg(14) deletion (R14del) mutations in PLN are associated with lethal dilated cardiomyopathy in humans", "We previously reported the deletion of the highly conserved amino acid residue arginine 14 (nucleic acids 39, 40 and 41) in DCM patients.", "Mutations in the gene encoding PLN have been associated with idiopathic dilated cardiomyopathy;", "Mutations in the PLN gene are a rare cause of heart failure, present almost exclusively in patients with dilated cardiomyopathy etiology", "A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death.", "Complete genetic and clinical analyses were performed in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation.", "A candidate gene approach resulted in identification of a heterozygous deletion of arginine 14 in the gene encoding phospholamban (PLN-R14Del) segregating with dilated cardiomyopathy in the family pedigree. Mutation carriers suffered from familial dilated cardiomyopathy associated with cardiac death between the ages of 26 and 50 years.", "a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation.", "For the phospholamban (PLN) and titin cap (TTN) genes, a direct mutation screening approach was used. DNA sequence analysis of all exons showed no evidence that these genes are involved in DCM in the Newfoundland dog.", "two human PLN mutations, associated with either absence or sustained dephosphorylation of PLN, were linked to dilated cardiomyopathy.", "Mutations in the gene encoding PLN have been associated with dilated cardiomyopathy characterized by early onset and the presence of lethal ventricular arrhythmias.", "The identical PLN mutation can be associated with both mild and severe forms of dilated cardiomyopathy. Additionally, PLN mutations should be considered in late onset 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 PLN gene mutation was found in patients with DCM in Chengdu. This result indicated that PLN gene mutation may not be a common cause for DCM in the Chinese population in Chengdu.", "none in PLN", "the recent discoveries of human PLN mutations leading to disease states.", "Strikingly, both individuals homozygous for L39stop developed dilated cardiomyopathy and heart failure, requiring cardiac transplantation at ages 16 and 27.", "humans lacking PLN develop lethal dilated cardiomyopathy.", "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)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20634894", "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "http://www.ncbi.nlm.nih.gov/pubmed/15336969", "http://www.ncbi.nlm.nih.gov/pubmed/15769782", "http://www.ncbi.nlm.nih.gov/pubmed/23349452", "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "http://www.ncbi.nlm.nih.gov/pubmed/17019811", "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "http://www.ncbi.nlm.nih.gov/pubmed/16235537", "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "http://www.ncbi.nlm.nih.gov/pubmed/19324307", "http://www.ncbi.nlm.nih.gov/pubmed/17998275", "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "http://www.ncbi.nlm.nih.gov/pubmed/22427649" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017354", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004106", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389", "http://www.uniprot.org/uniprot/PPLA_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054643", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020125", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004252", "http://www.uniprot.org/uniprot/PPLA_RAT", "http://www.uniprot.org/uniprot/PPLA_RABIT", "http://www.uniprot.org/uniprot/PPLA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004108", "http://www.uniprot.org/uniprot/PPLA_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016368", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.uniprot.org/uniprot/PPLA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017384", "http://www.uniprot.org/uniprot/PPLA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ]

[ "The genetic lesion associated with Huntington's disease is a CAG trinucleotide repeat expansion in the HD (or HTT) gene." ]

[ "A CAG trinucleotide repeat expansion in the HD gene" ]

[ "Early in 1993, an unstable, expanded trinucleotide repeat in a novel gene of unknown function was identified on HD chromosomes. This discovery unleased a flurry of experimentation that has established the expanded CAG repeat the almost universal cause of the characteristic neurologic symptoms and pathology of this neurodegenerative disorder of midlife onset." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7620118" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.disease-ontology.org/api/metadata/DOID:12858", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006816", "http://www.uniprot.org/uniprot/HD_HUMAN", "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:630", "http://www.disease-ontology.org/api/metadata/DOID:0050325" ]

[ "Yes, agenesis of the corpus callosum is common patients with Mowat–Wilson syndrome. Other characteristic features of Mowat–Wilson syndrome include typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, and eye defects." ]

[ "yes" ]

[ " The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. ", "Mowat-Wilson syndrome in a fetus with antenatal diagnosis of short corpus callosum: advocacy for standard autopsy.", "It is mainly characterized by moderate-to-severe intellectual disability, epilepsy, facial dysmorphism and various malformations including Hirschsprung disease and corpus callosum anomalies. ", "The association of a corpus callosum hypoplasia with a histological Hirschsprung disease and a typical facial gestalt allowed the guiding of genetic testing.", "Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR). ", "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations.", "Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations.", "The striking facial phenotype in addition to other features such as severely impaired speech, hypotonia, microcephaly, short stature, seizures, corpus callosum agenesis, congenital heart defects, hypospadias, and Hirschsprung disease are particularly important clues for the initial clinical diagnosis. ", "Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies. ", "It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. ", "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies.", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects. ", "Agenesis or hypogenesis of the corpus callosum.", "The anomalies may include Hirschsprung disease, heart defects, structural eye anomalies including microphthalmia, agenesis of the corpus callosum, and urogenital anomalies. ", "Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects.", "In 11 of the 28 patients with ACC, the following diagnoses could be established: Mowat-Wilson syndrome (n = 2), Walker-Warburg syndrome (n = 1), oro-facial-digital syndrome type 1 (n = 1), and chromosomal rearrangements (n = 7), including a patient with an apparently balanced reciprocal translocation, which led to the disruption and a predicted loss of function in the FOXG1B gene.", "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "http://www.ncbi.nlm.nih.gov/pubmed/23531534", "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "http://www.ncbi.nlm.nih.gov/pubmed/15065106", "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "http://www.ncbi.nlm.nih.gov/pubmed/23243526", "http://www.ncbi.nlm.nih.gov/pubmed/12746390", "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "http://www.ncbi.nlm.nih.gov/pubmed/23322667", "http://www.ncbi.nlm.nih.gov/pubmed/16053902", "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "http://www.ncbi.nlm.nih.gov/pubmed/19215041", "http://www.ncbi.nlm.nih.gov/pubmed/20301585", "http://www.ncbi.nlm.nih.gov/pubmed/22246645", "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/17103451", "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "http://www.ncbi.nlm.nih.gov/pubmed/18792984", "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "http://www.ncbi.nlm.nih.gov/pubmed/24401652", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/16088920" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003337", "http://www.disease-ontology.org/api/metadata/DOID:225" ]

[ "Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. " ]

[ "H3K4me1", "H3K27ac" ]

[ "Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancer", "Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.", "We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury.", "However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury.", "Recent studies using mammalian cells showed that a chromatin state signature is associated with active developmental enhancers, defined by high levels of histone H3 lysine 27 acetylation (H3K27ac) and strong depletion of H3K27 trimethylation (H3K27me3", "Such permissive binding was largely restricted to open-chromatin regions showing histone modification marks characteristic of active enhancer and promoter regions, whereas open-chromatin regions lacking such marks did not show permissive binding. ", "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone", "The bivalent hypothesis posits that genes encoding developmental regulators required for early lineage decisions are poised in stem/progenitor cells by the balance between a repressor histone modification (H3K27me3), mediated by the Polycomb Repressor Complex 2 (PRC2), and an activator modification (H3K4me3)", "Histone H3K27ac separates active from poised enhancers and predicts developmental state", "Histone H3K27ac separates active from poised enhancers and predicts developmental state.", "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. ", "Furthermore, we compare the ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate that eRNA is more indicative of enhancer activity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21632746", "http://www.ncbi.nlm.nih.gov/pubmed/25614629", "http://www.ncbi.nlm.nih.gov/pubmed/23595227", "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "http://www.ncbi.nlm.nih.gov/pubmed/23880941", "http://www.ncbi.nlm.nih.gov/pubmed/23166019", "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "http://www.ncbi.nlm.nih.gov/pubmed/25250711" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421" ]

[ "Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation. In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification. Super-enhancers thus play key roles in the control of mammalian cell identity." ]

[ "their magnitude of size", "transcription factor density", "binding of transcriptional machinery", "associated with genes driving cell differentiation" ]

[ "Here we report that enhancer RNAs (eRNAs) identified by global nuclear run-on sequencing are extensively transcribed within super enhancers and are dynamically regulated in response to cellular signaling.", "Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs", "The expression of genes that specify cell type identity and function is associated with densely spaced clusters of active enhancers known as super-enhancers. The functions of enhancers and super-enhancers are influenced by, and affect, higher-order genomic organization.", " Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation.", "Here we review evidence for super-enhancer involvement in cancers, complex diseases, and developmental disorders and discuss interactions between super-enhancers and cofactors/chromatin regulators.", "The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq).", "In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification.", "Super-enhancers (SEs), also known as stretch-enhancers, are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease. CD4(+) T cells are critical for host defence and autoimmunity.", "Super-enhancers and stretch enhancers (SEs) drive expression of genes that play prominent roles in normal and disease cells, but the functional importance of these clustered enhancer elements is poorly understood, so it is not clear why genes key to cell identity have evolved regulation by such elements", "Super-enhancers thus provide a platform for signaling pathways to regulate genes that control cell identity during development and tumorigenesis.", "Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo.", "We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression.", "New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another.", "Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.", "We demonstrate that hotspots are highly enriched in large super-enhancer regions (several kilobases), which drive the early adipogenic reprogramming of gene expression.", "Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers constitute important regulatory hubs that serve to integrate external stimuli on chromatin.", "We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.", "Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation", "Super-enhancers thus play key roles in the control of mammalian cell identity.", "Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity.", "We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. ", "Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.", "Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs.", "NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.", "Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25686607", "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "http://www.ncbi.nlm.nih.gov/pubmed/25650801", "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "http://www.ncbi.nlm.nih.gov/pubmed/25263595", "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "http://www.ncbi.nlm.nih.gov/pubmed/25801169", "http://www.ncbi.nlm.nih.gov/pubmed/24857652" ]

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[]

[ "Li-Fraumeni syndrome shows autosomal dominant inheritance." ]

[ "Autosomal dominant" ]

[ "It therefore appears that the LFS phenotype has been conferred by an aberrant gene, showing a dominant pattern of inheritance, which may be acting to compromise normal p53 function rather than by a mutation in p53 itself.", "In addition, there seem to be predispositions to a wider range of different, but well-defined neoplasms: e.g., adenocarcinomatosis of the colon and the endometrium, or the Li-Fraumeni/SBLA syndrome. The latter shows a spectrum of sarcoma, brain tumours, breast cancer, leukaemias, lung and adenocortical cancer. The genes leading to these types of dominantly inherited predispositions appear to be the tentatively so-called tumour suppressor genes, for which the Rb gene serves as a model", "he Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family.", "Li-Fraumeni Syndrome (LFS) is characterized by early-onset carcinogenesis involving multiple tumor types and shows autosomal dominant inheritance.", "BACKGROUND: Li-Fraumeni-Syndrome (LFS) is an autosomal-dominant, inherited tumour predisposition syndrome associated with heterozygous germline mutations in the TP53 gene.", "Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant, human familial cancer predisposition", "The Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2190528", "http://www.ncbi.nlm.nih.gov/pubmed/7981072", "http://www.ncbi.nlm.nih.gov/pubmed/16772121", "http://www.ncbi.nlm.nih.gov/pubmed/9302689", "http://www.ncbi.nlm.nih.gov/pubmed/22672556", "http://www.ncbi.nlm.nih.gov/pubmed/20075382" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2961", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/679" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2961", "o": "Li Fraumeni syndrome, 151623" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/679", "o": "Li_Fraumeni_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16615981", "o": "OMIM" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2675080", "o": "http://linkedlifedata.com/resource/umls/label/A16619828" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16615981", "o": "LI-FRAUMENI-LIKE SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16619828", "o": "LFL" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2675080", "o": "http://linkedlifedata.com/resource/umls/label/A16615981" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16619828", "o": "OMIM" } ]

[ "http://www.disease-ontology.org/api/metadata/DOID:3012", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "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=D016864" ]

[ "Prolactinoma is a pituitary adenoma that is strongly associated with infertility in women mainly due to increased prolactin secretion causing hyperprolactinemia. Other pituitary lesions can also be associated with infertility." ]

[ "prolactinoma" ]

[ "Prolactinoma is the most common secreting pituitary adenoma. It is typically diagnosed in women of reproductive age and is common cause of infertility.", "Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH. RESULTS: Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy.", "CONCLUSIONS: Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration.", "Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis, occurring mostly in women and presenting most commonly with amenorrhea and galactorrhea. Causes of hyperprolactinemia include physiologic, pharmacologic and pathologic factors; pituitary adenoma is a common pathologic cause. Women may present with decreased libido, infertility, oligomenorrhea/amenorrhea and galactorrhea.", "When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea).", "Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause infertility.", "Of the remaining six patients who had been investigated for infertility, no demonstrable cause of infertility was found in three. Of the other three patients, one showed evidence of bilateral tubal occlusion secondary to pelvic inflammatory disease, one has had a right ectopic pregnancy followed by two abortions, and the third patient was found to have a pituitary adenoma.", "Results in 136 hyperprolactinaemic women who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea are reported. There was radiographic evidence of pituitary microadenoma in 21 (15.4%) patients and 5 (3.7%) had macroadenoma.", "Patients with pituitary adenoma had a significantly higher (p less than 0.001) baseline serum prolactin level (182 +/- 4.6 ng/ml) than those with no adenoma (59.2 +/- 4.2 ng/ml). All patients in the study were treated with bromocriptine (2.5-10 mg) to normalize serum prolactin or to achieve a pregnancy.", "There was no significant difference in the pregnancy rate between the patients with or without pituitary adenoma.", "Two hyperprolactinemic infertile women, one with and one without a pituitary adenoma, who were resistant to bromocriptine treatment, were treated orally with Hachimijiogan, a Chinese herbal medicine.", "Infertility caused by hyperprolactinemic amenorrhea may be complicated by pituitary adenoma." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9152623", "http://www.ncbi.nlm.nih.gov/pubmed/23090264", "http://www.ncbi.nlm.nih.gov/pubmed/2803131", "http://www.ncbi.nlm.nih.gov/pubmed/12477530", "http://www.ncbi.nlm.nih.gov/pubmed/2738821", "http://www.ncbi.nlm.nih.gov/pubmed/10649814", "http://www.ncbi.nlm.nih.gov/pubmed/10649815", "http://www.ncbi.nlm.nih.gov/pubmed/2520800", "http://www.ncbi.nlm.nih.gov/pubmed/6788711", "http://www.ncbi.nlm.nih.gov/pubmed/6868876" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015175", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007247", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007246", "http://www.disease-ontology.org/api/metadata/DOID:5394", "http://www.disease-ontology.org/api/metadata/DOID:5395", "http://www.disease-ontology.org/api/metadata/DOID:5223", "http://www.disease-ontology.org/api/metadata/DOID:3829", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010911" ]

[ "The mismatch-specific uracil DNA glycosylase (MUG) belongs to a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. The crystal structure of the Mug repair complex points to a preference of Mug for G:U over G:T mispairs. Nonetheless, Mug does not repair U:G or T:G mismatches in vivo. Mug possesses xanthine DNA glycosylase (XDG) activity in E.coli. The repair activity of Mug is more robust against xanthine than uracil. Furthermore, Mug excises the alkylated base, 3, N(4)-ethenocytosine (epsilonC) from epsilonC:G mismatches, and may be the only enzyme in E.coli that can remove this mutagenic adduct. Thus, the principal role of Mug may be the repair of DNA damages caused by exogenous chemical agents such as chloroacetaldehyde." ]

[]

[ "XDG activity is attributable to MUG", "xanthine DNA glycosylase (XDG) activity in E. coli", "The wild type MUG possesses more robust activity against xanthine than uracil and is active against all xanthine-containing DNA", "The gene for the mismatch-specific uracil DNA glycosylase (MUG) was identified in the Escherichia coli genome as a sequence homolog of the human thymine DNA glycosylase with activity against mismatched uracil base pairs.", "The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches.", "the principal role of Mug in E. coli may be to help repair damage to DNA caused by exogenous chemical agents such as chloroacetaldehyde", "excise epsilonC. The latter activity is missing in extracts from mug cells, suggesting that Mug may be the only enzyme in E. coli that can remove this mutagenic adduct. ", "Base-excision of a self-complementary oligonucleotide with central G:T mismatches by the G:T/U-specific mismatch DNA glycosylase (MUG)", "Mug does not repair U.G or T.G mismatches in vivo.", "remove 3,N(4)-ethenocytosine (epsilonC) from epsilonC.G mismatches", "The human thymine-DNA glycosylase has a sequence homolog in Escherichia coli that is described to excise uracils from U.G mismatches", "The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine.", "One member of the uracil-DNA glycosylase family of repair enzymes, Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug), is reported to distinguish U:G mispairs from U:A base pairs based upon specific contacts with the mispaired guanine after flipping the target uracil out of the duplex.", "T transition in the ung mug double mutant as compared to the single ung mutant suggest that MUG may be a back-up repair enzyme to the classic uracil-DNA glycosylase.", "The human thymine-DNA glycosylase has a sequence homolog in Escherichia coli that is described to excise uracils from U.G mismatches (Gallinari, P., and Jiricny, J. (1996) Nature 383, 735-738) and is named mismatched uracil glycosylase (Mug).", "Because uracil-DNA glycosylase (Ung) and Vsr are known to repair U.G and T.G mismatches, respectively, we conclude that Mug does not repair U.G or T.G mismatches in vivo.", "Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway.", "Role of mismatch-specific uracil-DNA glycosylase in repair of 3,N4-ethenocytosine in vivo.", "Thus, the principal role of Mug in E. coli may be to help repair damage to DNA caused by exogenous chemical agents such as chloroacetaldehyde.", "The role of the Escherichia coli mug protein in the removal of uracil and 3,N(4)-ethenocytosine from DNA.", "The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches", "The gene for the mismatch-specific uracil DNA glycosylase (MUG) was identified in the Escherichia coli genome as a sequence homolog of the human thymine DNA glycosylase with activity against mismatched uracil base pairs", "One member of the uracil-DNA glycosylase family of repair enzymes, Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug), is reported to distinguish U:G mispairs from U:A base pairs based upon specific contacts with the mispaired guanine after flipping the target uracil out of the duplex", "Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway", "Because uracil-DNA glycosylase (Ung) and Vsr are known to repair U.G and T.G mismatches, respectively, we conclude that Mug does not repair U.G or T.G mismatches in vivo" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12016206", "http://www.ncbi.nlm.nih.gov/pubmed/11841206", "http://www.ncbi.nlm.nih.gov/pubmed/21112870", "http://www.ncbi.nlm.nih.gov/pubmed/15474419", "http://www.ncbi.nlm.nih.gov/pubmed/9699633", "http://www.ncbi.nlm.nih.gov/pubmed/11555290", "http://www.ncbi.nlm.nih.gov/pubmed/10581234", "http://www.ncbi.nlm.nih.gov/pubmed/12482242", "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "http://www.ncbi.nlm.nih.gov/pubmed/9489705", "http://www.ncbi.nlm.nih.gov/pubmed/12531390", "http://www.ncbi.nlm.nih.gov/pubmed/10339434", "http://www.ncbi.nlm.nih.gov/pubmed/12184783" ]

[]

[ "http://www.uniprot.org/uniprot/MUG_SHIBS", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016798", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004844", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053843", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043739", "http://www.uniprot.org/uniprot/MUG_CITK8", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051981", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281" ]

[ "Thyronamines have negative chronotropy, negative inotropy; in particular thyronamines are considered negative inotropic agents", "In the heart, thyronamines cause negative chronotropy, negative inotropy,reduced cardiac output and resistance to ischemic injury." ]

[ "negative chronotropy", "lower heart rate", "negative inotropy", "negative inotropism", "resistance to ischemic injury", "reduced cardiac output" ]

[ "Most recently, thyroid hormone derivatives were identified, the thyronamines which are decarboxylated thyroid hormones initiating physiological actions like lowering body temperature and heart rate, thereby acting in opposite direction to the classical thyroid hormones.", "Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. ", "Functional effects have been observed after administration of exogenous T(1)AM: in the isolated heart, a negative inotropic and chronotropic action was produced, and the resistance to ischemic injury was increased, possibly as a consequence of an action on intracellular calcium homeostasis.", "Octopamine, beta-phenylethylamine, and tryptamine produced a dose-dependent negative inotropic effect as shown by reduced cardiac output (IC(50)=109 microM, 159 microM, and 242 microM, respectively). In the same preparation a similar effect was produced by thyronamine and 3-iodothyronamine, with IC(50)=94 microM and 27 microM, respectively. ", "A class of thyroid hormone metabolites has dramatic physiological effects on metabolism and heart rate by still-unknown mechanisms of action. ", "In the mouse, thyronamines act rapidly in a nongenomic fashion to initiate hypothermia and decrease cardiac output and heart rate." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/17579492", "http://www.ncbi.nlm.nih.gov/pubmed/21835056", "http://www.ncbi.nlm.nih.gov/pubmed/19016324", "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "http://www.ncbi.nlm.nih.gov/pubmed/17204552", "http://www.ncbi.nlm.nih.gov/pubmed/19273499", "http://www.ncbi.nlm.nih.gov/pubmed/20739399", "http://www.ncbi.nlm.nih.gov/pubmed/18486124", "http://www.ncbi.nlm.nih.gov/pubmed/22073124" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.biosemantics.org/jochem#4251308", "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=D002302" ]

[ "Matuzumab has been tested for treatment of non-small cell lung, gastric, esophageal, colorectal, primary peritoneal, pancreatic, ovarian and cervical cancers." ]

[ "non-small cell lung", "gastric", "esophageal", "colorectal", "primary peritoneal", "pancreatic", "ovarian", "cervical" ]

[ " Matuzumab and panitumumab have also been studied in phase II trials.", "A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer.", "This phase I study investigated the tolerability, safety and pharmacokinetics (PK) of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer (NSCLC). ", "Matuzumab combined with paclitaxel was generally well tolerated in patients with advanced NSCLC. ", "This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib.", "Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.", "BACKGROUND: To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas.", "Matuzumab and panitumumab have also been evaluated in phase II trials. ", "Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer.", "INTRODUCTION: This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. ", "Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study.", "BACKGROUND: Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. ", " CONCLUSION: Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer.", "In all studies, the patients had different types of advanced carcinoma - mainly colon, rectal and pancreatic cancer. They received matuzumab as multiple 1-hour intravenous infusions in a wide range of dosing regimens (development dataset: from 400 mg every 3 weeks to 2000 mg in the first week followed by 1600 mg weekly; evaluation dataset: from 100 mg weekly to 800 mg weekly). ", " Other anti-EGFR monoclonal antibodies, such as panitumumab, matuzumab, nimotuzumab, and ch806, are in different stages of development for the treatment of advanced NSCLC.", "Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer.", "Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with non-small cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel.", "Our data suggest that EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC.", "Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.", "To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). ", "Therefore, these first successes led to the development of several drugs including monoclonal antibodies (trastuzumab, panitumumab, matuzumab), TK inhibitors targeting one receptor as well as TK pan-inhibitors (lapatinib, HKI 272, PKI 166, EKB-569, AEE-788), currently assessed through clinical trials worldwide.", "Antibodies to the epidermal growth factor receptor in non small cell lung cancer: current status of matuzumab and panitumumab.", "Matuzumab and panitumumab are antibodies against the epidermal growth factor receptor (EGFR) that are being evaluated in several malignancies including non-small cell lung cancer (NSCLC). In phase I trials of single-agent matuzumab in patients with EGFR-positive cancer, three tumor responses were documented in esophageal squamous cell carcinoma as well as colorectal carcinoma.", "A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies.", "CONCLUSIONS: Matuzumab at the dose and schedule selected is well tolerated. In this population of very heavily pretreated patients with epithelial ovarian and primary peritoneal malignancies, there was no evidence of significant clinical activity when matuzumab was administered as monotherapy.", "Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer.", " Three groups of chemotherapy-naive advanced pancreatic adenocarcinoma patients (n=17) received escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly) and gemcitabine (1000 mg m-2 weekly in weeks 1-3 of each 4-week cycle). ", "A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC).", "This phase I study assessed the tolerability, pharmacokinetics and efficacy of the combination of matuzumab and paclitaxel in patients with advanced NSCLC.", "Other anti-EGFR monoclonal antibodies (panitunumab, matuzumab) are currently evaluated. ", "It is the target for a class of agents at the forefront of development for the treatment of colorectal cancer, ie, the anti-EGFR monoclonal antibodies, which include cetuximab, panitumumab, and matuzumab. ", "Two other monoclonal antibodies, matuzumab (EMD 72000) and panitumumab (ABG-EGF), also have shown activity against EGFR-expressing CRC but are still in the early stage of clinical development.", "Matuzumab is currently undergoing phase II clinical trials for gastric, cervical, pancreatic and ovarian cancers." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17671148", "http://www.ncbi.nlm.nih.gov/pubmed/18181050", "http://www.ncbi.nlm.nih.gov/pubmed/17126894", "http://www.ncbi.nlm.nih.gov/pubmed/19482958", "http://www.ncbi.nlm.nih.gov/pubmed/16857825", "http://www.ncbi.nlm.nih.gov/pubmed/22763610", "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "http://www.ncbi.nlm.nih.gov/pubmed/20497967", "http://www.ncbi.nlm.nih.gov/pubmed/16533873", "http://www.ncbi.nlm.nih.gov/pubmed/22807624", "http://www.ncbi.nlm.nih.gov/pubmed/16622465", "http://www.ncbi.nlm.nih.gov/pubmed/22832803", "http://www.ncbi.nlm.nih.gov/pubmed/15871762", "http://www.ncbi.nlm.nih.gov/pubmed/19433372", "http://www.ncbi.nlm.nih.gov/pubmed/19238629", "http://www.ncbi.nlm.nih.gov/pubmed/16387666", "http://www.ncbi.nlm.nih.gov/pubmed/19691369", "http://www.ncbi.nlm.nih.gov/pubmed/20978446", "http://www.ncbi.nlm.nih.gov/pubmed/15011787", "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "http://www.ncbi.nlm.nih.gov/pubmed/16336753", "http://www.ncbi.nlm.nih.gov/pubmed/19276157" ]

[]

[]

[ "Prostate-specific antigen (PSA) is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases which is produced by epithelial cells of both normal and malignant prostate tissue. PSA is an important marker for the diagnosis of prostate cancer. PSA is also known as human kallikrein-related peptidase 3 (hK3).", "Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. (PMID: 19079621)" ]

[ "human kallikrein-related peptidase 3", "hK3" ]

[ "Evidence for the novel expression of human kallikrein-related peptidase 3, prostate-specific antigen, in the brain.", "Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19079621" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020840", "http://www.uniprot.org/uniprot/KLK2_CAVPO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017430", "http://www.uniprot.org/uniprot/KLK3_MACFA", "http://www.uniprot.org/uniprot/KLK3_HUMAN" ]

[ "Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands." ]

[ "lipid storage and lipid mobilization" ]

[ "Eukaryotic cells store excess fatty acids as neutral lipids, predominantly triacylglycerols and sterol esters, in organelles termed lipid droplets (LDs) that bulge out from the endoplasmic reticulum. ", "Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage.", "Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). ", "Lipid droplets are found in all cell types", "Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. ", "Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26121906", "http://www.ncbi.nlm.nih.gov/pubmed/25189622", "http://www.ncbi.nlm.nih.gov/pubmed/25132820", "http://www.ncbi.nlm.nih.gov/pubmed/24394544", "http://www.ncbi.nlm.nih.gov/pubmed/25894691", "http://www.ncbi.nlm.nih.gov/pubmed/25110833" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "MTHU008985" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1848739", "o": "http://linkedlifedata.com/resource/umls/label/A12002602" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "Lipid droplets in granulocytes" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1848739", "o": "http://linkedlifedata.com/resource/umls/label/A12002602" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16505206", "o": "GO:0034430" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2612536", "o": "http://linkedlifedata.com/resource/umls/label/A16505206" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2612536", "o": "http://linkedlifedata.com/resource/umls/label/A16505206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16505206", "o": "lipid droplet outer lipid monolayer" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "MTHU008988" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1848740", "o": "http://linkedlifedata.com/resource/umls/label/A11988246" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "Lipid droplets in basal keratinocytes" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1848740", "o": "http://linkedlifedata.com/resource/umls/label/A11988246" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellType", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://purl.uniprot.org/tissues/12" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000B" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000C" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/12", "o": "Adipocytes" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000B", "o": "Perilipin-1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/12", "o": "Adipocyte" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000C", "o": "Lipid droplet-associated protein" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellType", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://purl.uniprot.org/tissues/12" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834009", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834008", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834008" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "OMIM" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005811", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D066292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034389", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ]

[ "Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. The biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression.", "Circular RNAs are new players in regulation of post transcriptional gene expression. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. This new type of transcript might represent a novel aspect of gene expression and hold some interesting clues about the splicing mechanism. Here we determine the structure of these novel transcripts, showing that they correspond to circular RNA molecules containing only exons in genomic order." ]

[ "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression." ]

[ "Here we determine the structure of these novel transcripts, showing that they correspond to circular RNA molecules containing only exons in genomic order.", "Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle.", "Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific.", "These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.", "Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs.", " For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.", "An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons.", "A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing.", "Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.", "Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome.", "CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are necessary for circRNA biogenesis.", "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression.", "Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. ", "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", "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. Herein, we review the breadth of circular RNAs, their biogenesis and metabolism, and their known and anticipated functions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/24039610", "http://www.ncbi.nlm.nih.gov/pubmed/24609083", "http://www.ncbi.nlm.nih.gov/pubmed/25404635", "http://www.ncbi.nlm.nih.gov/pubmed/7678559" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ]

[ "No. 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective." ]

[ "no" ]

[ "Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria", "This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. ", "The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. ", "OKN-007 is a proprietary compound that has had extensive commercial development (designated as NXY-059) for another indication, acute ischemic stroke, and after extensive clinical studies was shown to lack efficacy for this indication but was shown to be very safe for human use. ", "NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II).", "NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke. ", "We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials", " In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? ", " In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.", "CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. ", "BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS).", "BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. ", "CONCLUSIONS: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms.", "The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial.", "The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. ", "The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. ", "NXY-059, a free radical spin trap agent, was felt by many to have followed these criteria and it was recently shown to improve outcome in AIS patients in the SAINT I trial. However, the repeat, SAINT II trial was a neutral study, the results of which cast doubt on neuroprotection as a viable strategy for AIS. ", "NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale.", "BACKGROUND AND PURPOSE: NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke.", "CONCLUSIONS: NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. ", "CONCLUSIONS: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. ", "BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke.", "NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke.", "The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke", "The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17408618", "http://www.ncbi.nlm.nih.gov/pubmed/21651461", "http://www.ncbi.nlm.nih.gov/pubmed/11239186", "http://www.ncbi.nlm.nih.gov/pubmed/18369171", "http://www.ncbi.nlm.nih.gov/pubmed/19167593", "http://www.ncbi.nlm.nih.gov/pubmed/17975102", "http://www.ncbi.nlm.nih.gov/pubmed/19074479", "http://www.ncbi.nlm.nih.gov/pubmed/19631615", "http://www.ncbi.nlm.nih.gov/pubmed/18416999", "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "http://www.ncbi.nlm.nih.gov/pubmed/23419732", "http://www.ncbi.nlm.nih.gov/pubmed/22709256", "http://www.ncbi.nlm.nih.gov/pubmed/16467546", "http://www.ncbi.nlm.nih.gov/pubmed/17478741", "http://www.ncbi.nlm.nih.gov/pubmed/17579658", "http://www.ncbi.nlm.nih.gov/pubmed/23109881", "http://www.ncbi.nlm.nih.gov/pubmed/17420989", "http://www.ncbi.nlm.nih.gov/pubmed/12848592", "http://www.ncbi.nlm.nih.gov/pubmed/17244778", "http://www.ncbi.nlm.nih.gov/pubmed/18673209", "http://www.ncbi.nlm.nih.gov/pubmed/17068304" ]

[]

[]

[ "Yes, flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder." ]

[ "yes" ]

[ "Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder.", "Flibanserin is a novel multifunctional serotonin agonist and antagonist (MSAA) that improves sexual functioning in premenopausal women who suffer from reduced sexual interest and desire.", "Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women.", "CONCLUSIONS: In naturally postmenopausal women with HSDD, flibanserin, compared with placebo, has been associated with improvement in sexual desire, improvement in the number of SSEs, and reduced distress associated with low sexual desire, and is well tolerated.", "INTRODUCTION: Flibanserin is a mixed 5-HT1A agonist/5-HT2A antagonist that has been developed for the treatment of hypoactive sexual desire disorder in women", "BACKGROUND: Flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder (HSDD). ", "Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. ", "Sexual function adverse events across flibanserin groups were generally comparable to placebo.Although these studies were not designed or powered to compare sexual function outcomes, results suggested a potential benefit of flibanserin on sexual function, particularly on female sexual desire, and provided a rationale to evaluate the efficacy of flibanserin as a treatment for female hypoactive sexual desire disorder." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20646181", "http://www.ncbi.nlm.nih.gov/pubmed/23421417", "http://www.ncbi.nlm.nih.gov/pubmed/25659981", "http://www.ncbi.nlm.nih.gov/pubmed/25187905", "http://www.ncbi.nlm.nih.gov/pubmed/24281236", "http://www.ncbi.nlm.nih.gov/pubmed/22727480" ]

[]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4266735", "http://www.biosemantics.org/jochem#4266735", "http://www.disease-ontology.org/api/metadata/DOID:13868" ]

[ "We live in an age of access to more information than ever before. The exponential growth in the volume of publications in the biomedical domain has made it impossible for an individual to keep pace with the advances. Thus, there is a need for intelligent information retrieval systems that can summarize relevant and reliable textual sources to satisfy a user's query. Question answering is a specialized type of information retrieval with the aim of returning precise short answers to queries posed as natural language questions. This accentuates the need for fast and accurate biomedical question answering systems. In this paper we introduce INDOC -- a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed. Increased access to information allows for more informed and empowered researchers, while information overload becomes an increasingly serious risk. INDOC displays the results in clusters to help the user arrive the most relevant set of documents quickly. Evaluation was done against the standard OHSUMED test collection. We present a review and comparison of three biomedical question answering systems: askHERMES, EAGLi ( http://eagl.unige.ch/EAGLi/ ), and HONQA ( http://services.hon.ch/cgi-bin/QA10/qa.pl ). ", "askHERMES, EAGLi, HONQA and INDOC." ]

[ "askHERMES", "EAGLi", "HONQA", "INDOC" ]

[ "Question answering is a specialized type of information retrieval with the aim of returning precise short answers to queries posed as natural language questions. We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl)", "Question processing and clustering in INDOC: a biomedical question answering system", "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed. INDOC displays the results in clusters to help the user arrive the most relevant set of documents quickly. Evaluation was done against the standard OHSUMED test collection. Our system achieves high accuracy and minimizes user effort", "Question processing and clustering in INDOC: a biomedical question answering system.", "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed.", "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.", "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed.", "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl).", "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl).", "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed", "Onelook is a portal for online definitions, and MedQA is a question answering system that automatically generates short texts to answer specific biomedical questions" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17990503", "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "http://www.ncbi.nlm.nih.gov/pubmed/18274647" ]

[]

[]

[ "Type 1 and Type 3 deiodinases are both present in liver" ]

[ "Type 1 deiodinase", "Tipe 3 deiodinase" ]

[ "Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney.", "Co-expression of the deiodinases was also found in the kidney.", "high ID-I activities were found in liver, kidney", "the kidney microsome 5'-deiodinase is type I." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15072569", "http://www.ncbi.nlm.nih.gov/pubmed/9794474", "http://www.ncbi.nlm.nih.gov/pubmed/3595535", "http://www.ncbi.nlm.nih.gov/pubmed/7768329", "http://www.ncbi.nlm.nih.gov/pubmed/3197644" ]

[]

[]

[ "Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. Failure of FANCD2 monoubiquitination by the nuclear FA protein complex has a severe impact on the DNA repair functions of cells." ]

[ "FANCD2 monoubiquitination" ]

[ "A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase", "Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links", "Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA", "Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. Eight FA-associated genes have been identified so far, the products of which function in the FA/BRCA pathway. A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex", " Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA.", "This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted.", "Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA.", "A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex.", "The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2-FANCI complex.", "FA proteins (FancA/C/E/F/G/L) form a multiprotein complex, which is responsible for DNA damage-induced FancD2 monoubiquitination, a key event for cellular resistance to DNA damage.", "A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase.", "A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex", "This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22675617", "http://www.ncbi.nlm.nih.gov/pubmed/15601828", "http://www.ncbi.nlm.nih.gov/pubmed/19609304", "http://www.ncbi.nlm.nih.gov/pubmed/20937699", "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "http://www.ncbi.nlm.nih.gov/pubmed/22258451", "http://www.ncbi.nlm.nih.gov/pubmed/15383454" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062" ]

[ "Allopurinol was shown in a number of clinical trial to be safe and effective for treatment of neonatal asphyxia. Allopurinol improves short-term and long-term clinical outcomes of neonatal asphyxia. Allopurinol should be administered as soon as possible. Postulated mechanism of allopurinol action in this setting is prevention of hypoxia-perfusion injury by reduction of free radical formation." ]

[]

[ "Potential neuroprotective strategies targeting different pathways leading to neuronal cell death in response to hypoxic-ischemic insult have been investigated: hypothermia, erythropoietin, iminobiotin, deferioxamine, magnesium, allopurinol, xenon, melatonin and statins.", "Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage.", "There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94).", "The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.", "The asphyxiated newborns treated with allopurinol had better neurologic and neurodevelopmental outcome at 12 or more months of age.", "In newborn infants, allopurinol is being tested as a free radical scavenger to prevent brain damage caused by reperfusion and oxygenation after perinatal hypoxia and ischemia (birth asphyxia).", "Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia.", "The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol.", "Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge.", "One randomized trial of allopurinol showed short-term benefits but was too small to test death or disability.", "No toxic side effects of ALLO were detected.", "This study suggests a beneficial effect of ALLO treatment on free radical formation, CBV, and electrical brain activity, without toxic side effects." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16428356", "http://www.ncbi.nlm.nih.gov/pubmed/17162192", "http://www.ncbi.nlm.nih.gov/pubmed/22564301", "http://www.ncbi.nlm.nih.gov/pubmed/22102633", "http://www.ncbi.nlm.nih.gov/pubmed/9445490", "http://www.ncbi.nlm.nih.gov/pubmed/16778717", "http://www.ncbi.nlm.nih.gov/pubmed/12436031", "http://www.ncbi.nlm.nih.gov/pubmed/20167117" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001238", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001237", "http://www.biosemantics.org/jochem#4273300", "http://www.disease-ontology.org/api/metadata/DOID:11088", "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=D000493" ]

[ "Currently there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting." ]

[ "no" ]

[ "Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality.", "We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.", "There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.", "Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended.", "Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.", "Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.", "Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "http://www.ncbi.nlm.nih.gov/pubmed/20668034", "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "http://www.ncbi.nlm.nih.gov/pubmed/12643405", "http://www.ncbi.nlm.nih.gov/pubmed/8633935", "http://www.ncbi.nlm.nih.gov/pubmed/12079930", "http://www.ncbi.nlm.nih.gov/pubmed/12800543", "http://www.ncbi.nlm.nih.gov/pubmed/1859661", "http://www.ncbi.nlm.nih.gov/pubmed/10343261", "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "http://www.ncbi.nlm.nih.gov/pubmed/16719939", "http://www.ncbi.nlm.nih.gov/pubmed/3872103", "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "http://www.ncbi.nlm.nih.gov/pubmed/8594265" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "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=D003331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001026" ]

[ "Neurofilament light protein (NFL), may be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS).\nNeurofilament light chain is a prognostic biomarker in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, multiple sclerosis and head trauma." ]

[]

[ "Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.", "CSF neurofilament light chain reflects corticospinal tract degeneration in ALS.", "Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders.", "Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome.", "Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury.", "Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD).", "We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.", "FL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.", "Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.", " The association of prolonged CSF NFL increase in boxers with impairment of processing speed is an interesting observation, which needs to be verified in larger studies.", "neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment", "Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.", "Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.", "Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.", " We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration", "CSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children", "Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia.", "he marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies.", "High levels of NFL also correlated with the presence of an AD biomarker pattern defined by Aβ42/P-tau and T-tau. ", "Increased CSF levels of T-tau, NFL, GFAP, and S-100B in>80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. ", "eurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). ", "A CSF profile with higher levels of NFL, Abeta42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology.", " At present we cannot recommend CSF NfH and NfL levels for use as a screening test in the diagnosis of dementia because of the rather small effect size. However, both neurofilament proteins may be of value for targeted investigation of some patients with FTLD, SVD and AD.", "Differences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.", "Increased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA). ", "Increased level of NFL is a general feature of MS, indicating continuous axonal damage during the entire course of the disease with the most profound damage during acute relapses. ", "Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24571714", "http://www.ncbi.nlm.nih.gov/pubmed/24479774", "http://www.ncbi.nlm.nih.gov/pubmed/24242746", "http://www.ncbi.nlm.nih.gov/pubmed/24073237", "http://www.ncbi.nlm.nih.gov/pubmed/23529999", "http://www.ncbi.nlm.nih.gov/pubmed/16894110", "http://www.ncbi.nlm.nih.gov/pubmed/24935984", "http://www.ncbi.nlm.nih.gov/pubmed/17290105", "http://www.ncbi.nlm.nih.gov/pubmed/25934855", "http://www.ncbi.nlm.nih.gov/pubmed/24523921", "http://www.ncbi.nlm.nih.gov/pubmed/23827424", "http://www.ncbi.nlm.nih.gov/pubmed/25192482", "http://www.ncbi.nlm.nih.gov/pubmed/21197541", "http://www.ncbi.nlm.nih.gov/pubmed/23763388", "http://www.ncbi.nlm.nih.gov/pubmed/22496755", "http://www.ncbi.nlm.nih.gov/pubmed/26273687", "http://www.ncbi.nlm.nih.gov/pubmed/20132991", "http://www.ncbi.nlm.nih.gov/pubmed/24941067", "http://www.ncbi.nlm.nih.gov/pubmed/23718879", "http://www.ncbi.nlm.nih.gov/pubmed/14694036", "http://www.ncbi.nlm.nih.gov/pubmed/17596713" ]

[]

[]

[ "Yes, the chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer." ]

[ "yes" ]

[ "Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC.", "CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. ", "The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. ", "The chemokine receptor CXCR4 that has been shown to be implicated in PDAC tumorigenicity and aggressiveness could serve as a prognostic marker for survival after a curative-intent surgery and was associated with the pattern of tumour recurrence (distant versus local relapse).", "XCR4 promotes tumor growth, angiogenesis and metastasis, and is a prognostic marker in a number of different types of tumors.", "CXCR4 has been identified as a prognostic marker for acute myeloid leukemia (AML) and other malignancies. ", "The chemokine receptor CXCR4 has been found to be a prognostic marker in various types of cancer, including breast cancer. ", "Upregulated expression of C-X-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer.", "detection of CXCR4 expression will be helpful for predicting prognosis for patients with gastric cancer.", "The chemokine receptor CXCR4 is a marker of metastatic disease.", "High CXCR4 level in cancer specimens independently predicts a poor outcome for patients with node-positive breast cancer.", "Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM.", "The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome. ", "high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20061818", "http://www.ncbi.nlm.nih.gov/pubmed/23822165", "http://www.ncbi.nlm.nih.gov/pubmed/23650783", "http://www.ncbi.nlm.nih.gov/pubmed/22473623", "http://www.ncbi.nlm.nih.gov/pubmed/21234386", "http://www.ncbi.nlm.nih.gov/pubmed/22075627", "http://www.ncbi.nlm.nih.gov/pubmed/24650104", "http://www.ncbi.nlm.nih.gov/pubmed/23213054", "http://www.ncbi.nlm.nih.gov/pubmed/23359227", "http://www.ncbi.nlm.nih.gov/pubmed/26221287", "http://www.ncbi.nlm.nih.gov/pubmed/23936528", "http://www.ncbi.nlm.nih.gov/pubmed/23395387" ]

[]

[]

[ "The thyroid hormone (TH) induced regulation of SERCA is mediated both by non-genomic and genomic actions.\nGenomic actions are mediated by the binding of T(3) receptors (TRs) to the thyroid response elements in the SERCA promotor and result in increased gene expression. \nThyroid hormone increases the transcription of SERCA 2 through three thyroid hormone response elements. \nData show that the regulation of cardiac SERCA by thyroid hormone is made at the pretranslational and possibly transcriptional level \nTRβ1 is shown to be coupled to the expression of SERCA in the heart\nAn increase of TR expression in the hypertrophied heart has been show to result in increased SERCA expression.\nInhibition of TRα1 by dronedarone does not change the expression of SERCA in the heart\nFindings show that SERCA 2 gene expression is regulated by TR isoform-specific interactions with transcription factor (MEF-2) \nHypothyroidism is accompanied by decreased expression of SERCA in the heart. T3 increases expression of the cardiac SERCA\nTH treatment can reverse the reduction in the ratio of SERCA to phospholamban expression which is found in postinfarcted hearts\nTH treatment results in increased expression of SERCA in hearts from banded rats" ]

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[ "Furthermore, using specific inhibitors of the TH-activated kinases, we show that the long-term effects of TH on the expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), alpha- and beta-myosin heavy chain (MHC) and cell growth are reverted, implying that what is initiated as a non-genomic action of the hormone interfaces with genomic effects.", "Hypothyroid neonates showed increased cholesterol levels and decreased expression of D1 in liver and of Serca-2 in heart, which were normalized with T3 treatment.", "ERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-mediated SERCA2 expression in cultured cardiomyocytes. FOG-2 physically interacts with thyroid hormone receptor-alpha1 and abrogated even high levels of T3-mediated SERCA2 promoter activity.", "A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH", "After TH treatment, AMI-THYR hearts expressed 71% alpha-MHC and 29% beta-MHC, P<0.05 versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P<0.05 versus SHAM and AMI.", "Because the binding of T(3) occupied receptors to the thyroid response elements in the SERCA promotor can increase gene expression", "These results demonstrate that increasing TR expression in the hypertrophied heart is associated with an improvement in contractile function and increased SERCA expression.", "Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression", "Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function", "Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration.", "while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased.", "the postnatal switch from beta- to alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers", "In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1,", "dditionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3-supplemented group.", "even mild chronic myocardial thyrotoxicosis, such as may occur in human hyperthyroidism, can cause tachycardia and associated changes in high energy phosphate compounds independent of an increase in SERCA II and alpha-MHC.", "Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-MHC and SERCA proteins", "Thyroid hormone (T3) increases the transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) gene (SERCA 2) through three thyroid hormone response elements.", "MEF-2a in combination with either T3R alpha 1 or T3R beta 1 isoforms resulted in a 2.5-fold increase in SERCA 2 transgene expression in the absence of T3. Addition of T3 did not induce any further increase in SERCA 2 expression when T3R alpha 1 and MEF-2a expression vectors were cotransfected. In contrast, in the presence of T3R beta 1 and MEF-2, the addition of T3 increased chlorampenicol acetyltransferase activity by an additional 2.2-fold to a total 5.5-fold increase.", "Our findings point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.", "These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2)", "These data demonstrate that T3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors.", "Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca(2+)-ATPase.", "The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established.", "The mRNA encoding the sarcoplasmic reticulum (SR) Ca2+ ATPase is highly influenced by thyroid hormone (T3) in the hearts of intact animals.", "Direct cellular effects of thyroid hormone have been implicated in modulating the expression of the myosin heavy chain (MHC) genes and the slow sarcoplasmic reticulum calcium adenosine triphosphatase (SR Ca(2+)-ATPase) gene." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11145561", "http://www.ncbi.nlm.nih.gov/pubmed/22975595", "http://www.ncbi.nlm.nih.gov/pubmed/15242794", "http://www.ncbi.nlm.nih.gov/pubmed/18658259", "http://www.ncbi.nlm.nih.gov/pubmed/10198194", "http://www.ncbi.nlm.nih.gov/pubmed/11470472", "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "http://www.ncbi.nlm.nih.gov/pubmed/9312172", "http://www.ncbi.nlm.nih.gov/pubmed/18274800", "http://www.ncbi.nlm.nih.gov/pubmed/16595628", "http://www.ncbi.nlm.nih.gov/pubmed/2142022", "http://www.ncbi.nlm.nih.gov/pubmed/1415533", "http://www.ncbi.nlm.nih.gov/pubmed/20232113", "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/1827123", "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "http://www.ncbi.nlm.nih.gov/pubmed/8779840" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0015349", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "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/THA_PIG", "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://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/THAA_DANRE", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/AT2A2_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "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_PAROL", "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", "http://www.uniprot.org/uniprot/AT2A2_MOUSE" ]

[ "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." ]

[ "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." ]

[ "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway.", "Some putative MYB, bHLH, and environmental stress-responsive transcription factor binding sites were detected in the PaDOD1 and PaDOD2 promoter regions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25436858", "http://www.ncbi.nlm.nih.gov/pubmed/19791510" ]

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