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Natural_sciences | Peter Esben-Petersen
Peter Esben-Petersen (18 December 1869 in Sverup near Silkeborg – 2 April 1942 in Silkeborg) was a Danish entomologist who specialised in world Neuroptera.
He was also interested in the Orthoptera, Ephemeroptera and other insects of Denmark.
Esben-Petersen was a teacher in Silkeborg. He was associated with the entomological series Danmarks Flora og Fauna. For his scientific work on world fauna he received an honorary degree from the University of Copenhagen. His insect collection is conserved in the Zoological Museum in Copenhagen (mainly, some parts are in the Natural History Museum in Aarhus ).
Partial list
| 36029456 | https://en.wikipedia.org/wiki?curid=36029456 |
Natural_sciences | David Harper (palaeontologist)
David A.T. Harper is a British palaeontologist, specialising in fossil brachiopods and numerical methods in palaeontology. He is Professor of Palaeontology in Earth Sciences, Principal of Van Mildert College, and Deputy Head of Colleges (Research and Scholarly Activities) in Durham University. In December 2014 he began his term as President of the Palaeontological Association.
Harper was previously Professor of Palaeontology and Head of Geology in the Natural History Museum of Denmark, University of Copenhagen. He has published over 10 books and monographs, including a couple of influential textbooks, as well as over 250 scientific articles and, together with Øyvind Hammer, the widely used software package PAST. In recent years he has been addressing some of the major events in the history of life, for example the Cambrian Explosion, Great Ordovician Biodiversification Event and the end Ordovician mass extinctions. His research programmes have taken him to many parts of the world including Chile, China, Greenland, Russia and Tibet.
His research has been recognized by foreign membership of the Royal Danish Academy of Sciences and Letters, an Einstein Professorship in the Chinese Academy of Sciences and a D.Sc. from Queen’s University Belfast.
| 36035966 | https://en.wikipedia.org/wiki?curid=36035966 |
Natural_sciences | Metal hydroxide
Metal hydroxides are hydroxides of metals.
Metal hydroxides are also known as strong bases. Many common metal hydroxides are made up from hydroxide ions and the ion of the particular metal that it is made up of. Example: When NaOH (sodium hydroxide) is dissolved in water, it forms OH ions and Na ions. Metal hydroxides ionize completely when dissolved, so that is why they are known as strong bases. Their pH is above 7, labeling them as bases. Since ions conduct electricity, metal hydroxides carry electricity very well when they are dissolved.
In soils, it is assumed that larger amounts of natural phenols are released from decomposing plant litter rather than from throughfall in any natural plant community. Decomposition of dead plant material causes complex organic compounds to be slowly oxidized (lignin-like humus) or to break down into simpler forms (sugars and amino sugars, aliphatic and phenolic organic acids), which are further transformed into microbial biomass (microbial humus) or are reorganized, and further oxidized, into humic assemblages (fulvic and humic acids), which bind to clay minerals and metal hydroxides.
| 36044328 | https://en.wikipedia.org/wiki?curid=36044328 |
Natural_sciences | August Ferdinand Kuwert
August Ferdinand Kuwert (15 October 1828, Nidden – 14 August 1894, Wernsdorf, südl. von Königsberg) was a German entomologist who specialised in Coleoptera.
He was a Rittergutsbesitzer (owner of an estate or Junker) near the Prussian town of Wernsberg. Kuwert described many new species of Passalidae, Cleridae, Helophoridae, Hydrophilidae, Hydraenidae, Elmidae, Heteroceridae and Dryopidae.
Partial list
| 36055918 | https://en.wikipedia.org/wiki?curid=36055918 |
Natural_sciences | List of sites and monuments in Kenya
This is a list of sites and monuments of historic value that are maintained by the National Museums of Kenya.
| 36057278 | https://en.wikipedia.org/wiki?curid=36057278 |
Natural_sciences | ANAEM
The Ankara Nuclear Research and Training Center (), known as ANAEM, is a nuclear research and training center of Turkey. The organization was established on August 18, 2010 as a subunit of Turkish Atomic Energy Administration (, TAEK) in its campus at Ankara University's Faculty of Science situated in Beşevler neighborhood in central Ankara. The organization consists of three divisions, which are engaged in education, training and public relations on nuclear matters.
| 36057380 | https://en.wikipedia.org/wiki?curid=36057380 |
Natural_sciences | Warren Samuel Fisher
Warren Samuel Fisher (1878–1971) was an American entomologist who specialised in Coleoptera.
He was employed by the National Museum of Natural History in Washington. Fisher was especially interested in Buprestidae and Cerambycidae.
| 36057709 | https://en.wikipedia.org/wiki?curid=36057709 |
Natural_sciences | UGC 5497
UGC 5497 is a dwarf galaxy, located about 12 million light years away in the constellation Ursa Major. It is a member of the M81 Group.
| 36106398 | https://en.wikipedia.org/wiki?curid=36106398 |
Natural_sciences | Edward Alexander Newell Arber
Edward Alexander Newell Arber (5 August 1870, London - 14 June 1918, Cambridge) was an English botanist and paleontologist.
He was a Professor at the University of Cambridge specialising in palaeobotany.
Partial list
| 36158900 | https://en.wikipedia.org/wiki?curid=36158900 |
Natural_sciences | Nikolai Cholodny
Nikolai Grigoryevich Cholodny (; 22 June 1882 – 4 May 1953) was an influential microbiologist who worked at the University of Kiev, Ukraine in the USSR during the 1930s.
He is known for the Cholodny–Went model, which he developed independently with Frits Warmolt Went of the California Institute of Technology.
Despite being associated with the same theory, the two men never actually met.
Cholodny worked in the A.V. Fomin Botanical Garden, attached to the University of Kiev.
He was one of the pioneers of the concept that microbes adhere to surfaces,
using the technique of first placing glass slides in earth for a measured time period,
then using a microscope to examine the slides.
The Prokaryote "Leptothrix cholodnii" is named after him.
In 1927 Cholodny proposed that the cells of the coleoptile are first polarized under the influence of uneven exposure to light, so growth hormone can diffuse more rapidly towards the side in the shade than in any other direction.
Went reached the same conclusion in 1928, and the two scientists' names have been attached to the controversial Cholodny–Went theory.
Selected works include:
In 1937 N. G. Cholodny and E. Ch. Sankewitsch published an article on "Influence of weak electric currents upon the growth of the coleoptile" in "Plant Physiology".
The same year he published an article on "Charles Darwin and the modern theory of tropisms" in "Science" magazine.
| 36172635 | https://en.wikipedia.org/wiki?curid=36172635 |
Natural_sciences | HARPS-N
HARPS-N, the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere is a high-precision radial-velocity spectrograph, installed at the Italian Telescopio Nazionale Galileo, a 3.58-metre telescope located at the Roque de los Muchachos Observatory on the island of La Palma, Canary Islands, Spain.
HARPS-N is the counterpart for the Northern Hemisphere of the similar HARPS instrument installed on the ESO 3.6 m Telescope at La Silla Observatory in Chile. It allows for planetary research in the northern sky which hosts the Cygnus and Lyra constellations. In particular it allows for detailed follow up research to Kepler mission planet candidates, which are located in the Cygnus constellation region.
The instrument's main scientific goals are the discovery and characterization of terrestrial super-Earths by combining the measurements using transit photometry and doppler spectroscopy which provide both, the size and mass of the exoplanet. Based on the resulting density, rocky (terrestrial) Super-Earths can be distinguished from gaseous exoplanets.
The HARPS-N Project is a collaboration between the Geneva Observatory (lead), the Center for Astrophysics in Cambridge (Massachusetts), the Universities of St. Andrews and Edinburgh, the Queen's University Belfast, the UK Astronomy Technology Centre and the Italian Istituto Nazionale di Astrofisica.
First light on sky was obtained by HARPS-N on March 27, 2012 and official operations started on August 1, 2012.
| 36174770 | https://en.wikipedia.org/wiki?curid=36174770 |
Natural_sciences | Dark radiation
Dark radiation (also dark electromagnetism) is a postulated type of radiation that mediates interactions of dark matter.
By analogy to the way photons mediate electromagnetic interactions between particles in the Standard Model (called "baryonic matter" in cosmology), dark radiation is proposed to mediate interactions between dark matter particles. Similar to dark matter particles, the hypothetical dark radiation does not interact with Standard Model particles.
There has been no notable evidence for the existence of such radiation, but since baryonic matter contains multiple interacting particle types, it is reasonable to suppose that dark matter does also. Moreover, it has been pointed out recently that the cosmic microwave background data seems to suggest that the number of effective neutrino degrees of freedom is more than 3.046, which is slightly more than the standard case for 3 types of neutrino. This extra degree of freedom could arise from having a non-trivial amount of dark radiation in the universe. One possible candidate for dark radiation is the sterile neutrino.
| 36177989 | https://en.wikipedia.org/wiki?curid=36177989 |
Natural_sciences | Thiosilanes
As a family thiosilanes refers to compounds of the form RSSiR'H2 with a S-Si bond between organic groups.
| 36190552 | https://en.wikipedia.org/wiki?curid=36190552 |
Natural_sciences | John Veevers
John James Veevers (13 October 1930 – 12 August 2018) was an Australian Professor of Geology and a fellow of the Australian Academy of Science.
Veevers is the son of George Stanley Veevers and Dulcie Annie (née James) and attended Newington College (1944–1947). In 1946 he won the Wigram Allen Scholarship, endowed by Sir George Wigram Allen, for General Proficiency. At the end of 1947 Veevers was named Dux of the College and received the Schofield Scholarship and Halse Rogers Prize. He went up to the University of Sydney and graduated as a Bachelor of Science in 1952 and a Master of Science in 1954.
Veevers was a cadet geologist at the Bureau of Mineral Resources, Geology and Geophysics, Canberra, (1948–1951), rising to geologist (1952–1960) and senior geologist 1961–1967. In 1968, he was appointed as a senior lecturer at Macquarie University and has since been an Associate Professor, Professor and Adjunct Professor of the Department of Earth and Planetary Sciences. He was awarded his PhD in 1956 from Imperial College London.
Veevers' multiple publications are held by the National Library of Australia.
| 36193445 | https://en.wikipedia.org/wiki?curid=36193445 |
Natural_sciences | Blanketing effect
The blanketing effect (also referred to as line blanketing or the line-blanketing effect) is the enhancement of the red or infrared regions of a stellar spectrum at the expense of the other regions, with an overall diminishing effect on the whole spectrum. The term originates in a 1928 article by astrophysicist Edward Arthur Milne, where it was used to describe the effects that the astronomical metals in a star's outer regions had on that star's spectrum. The name arose because the absorption lines act as a "blanket", causing the continuum temperature of the spectrum to rise over what it would have been if these lines were not present.
Astronomical metals, which produce most of a star's spectral absorption lines, absorb a fraction of the star's radiant energy (a phenomenon known as the "blocking effect") and then re-emit it at a lower frequency as part of the "backwarming" effect. The combination of both these effects results in the position of stars in a color-color diagram to shift towards redder areas as the proportion of "metals" in them increases. The blanketing effect is thus highly dependent on the metallicity index of a star, which indicates the fraction of elements other than hydrogen and helium that compose it.
| 36197961 | https://en.wikipedia.org/wiki?curid=36197961 |
Natural_sciences | Conversion electron Mössbauer spectroscopy
Conversion electron Mössbauer spectroscopy (CEMS) is a Mössbauer spectroscopy technique based on conversion electron.
The CEM spectrum can be obtained either by collecting essentially all the electrons leaving the surface (integral technique), or by selecting the ones in a given energy range by means of a beta ray spectrometer (differential or depth selective CEMS).
This method allows the use of simple and inexpensive detecting equipment, mainly flow-type proportional detectors in which large counting rates can be obtained. This last characteristic makes possible the study of samples with the natural abundance of the Mössbauer isotope. The information furnished by the integral measurements can be increased by using various angles of incidence or by depositing thin layers of inert material on the sample.
In the energy range used in CEMS, the incident radiation can interact with the absorber through two kinds of processes: (a) conventional interactions – photoelectric and Compton effects, and (b) nuclear resonant absorption – Mössbauer effect. Due to conventional interactions the beam is attenuated and electrons are emitted from the sample. The nuclear de-excitation following the resonant absorption takes place by emission of either a gamma ray or an internal conversion (IC) electron. In the latter case, the atom is left in an ‘excited’ state with a hole in an inner shell; the energy excess is given away with emission of Auger electrons and/or X-rays. Thus, the electrons emitted from the sample as a consequence of the Mössbauer absorptions are: (a) primary (IC or Auger) electrons originated in the de-excitations of the nuclei excited by the incident beam, and (b) secondary electrons originated by conventional interactions of photons (or resonant absorption of gamma rays) emitted after resonant absorptions.
| 36216090 | https://en.wikipedia.org/wiki?curid=36216090 |
Natural_sciences | Beni Abbes Museum
Beni Abbes Museum also known as (Béni Abbès Museum) () is an art museum located in oasis town of Beni Abbes, Béchar Province, Algeria. It is "a resource dedicated to desert fauna, fossils and Algerian arts and crafts."
Béni Abbès Museum is popular in Algeria. It is supported by the Saharan Research Center. The museum houses displays desert fauna, fossils and traditional arts and crafts, such as carpets, wall hangings, ceramic items, woodcarvings and jewelry. The museum, which is supported by the Saharan Research Center, displays an extensive range of different types of dates. Dates are one of the mainstay crops of oasis towns and villages in Algeria.
The oasis of Beni Abbes has its own myth. Local people claim that:
The town of Beni Abbès is a popular tourist destination and the museum provides insights into its history and culture.
| 36231456 | https://en.wikipedia.org/wiki?curid=36231456 |
Natural_sciences | Meta-operator
In theoretical physics, the word meta-operator is sometimes used to refer to a specific operation over a combination of operators, as in the example of path-ordering. A meta-operator is different from an operator in that it does not correspond to a linear transform in the Hilbert space.
| 36235324 | https://en.wikipedia.org/wiki?curid=36235324 |
Natural_sciences | Yao Tandong
Yao Tandong (; born July 1954 in Gansu) is a Chinese glaciologist, a member of the Chinese Academy of Sciences (CAS). He served as Director of the CAS Institute of Tibetan Plateau Research (ITP) in Beijing. He is the first Asian scientist to win the prestigious Vega Medal in 2017 in the fields of anthropology and geography for his contribution to research on glaciers and the environment on the Tibetan Plateau.
Yao received his B.S. in 1978 and M.S in 1982 both from the Department of Geography, Lanzhou University in Gansu, China. He received his Ph.D from the Institute of Geographic Sciences and Natural Resources Research (IGSNRR), Chinese Academy of Sciences (CAS) in 1986. He worked as post-doctor in France and the USA from 1987 to 1990.
He worked at Cold and Arid Regions Environmental and Engineering Research Institute (CAREERI), CAS, which was formerly known as Lanzhou Institute of Glaciology and Geocryology, from 1990 to 2003 and was deputy director of the institute from 1995 to 2000 and director from 2000 to 2003. He has been director of the Institute of Tibetan Plateau Research (ITP), CAS since its founding in 2003.
Yao received awards for his research including the Natural Science Award and the Ho Leung Ho Lee Prize. He was recognized by the Science Association of China with a "Distinguished Scientist of China" award in 2005. Yao was elected to the Chinese Academy of Sciences in 2007.
| 36236193 | https://en.wikipedia.org/wiki?curid=36236193 |
Natural_sciences | John Grattan
John Grattan (1800, Dublin -1871) was an Irish naturalist and anthropologist.
John Grattan was an apothecary in Belfast. He had wide interests in natural history and was a member of the Belfast Natural History Society but is best known for his work on ancient Irish skulls collected by his friend Edmund Getty. He devised a system of skull measurements using an ingenious craniometer. "Grattan's work was almost contemporaneous with that of Anders Retzius, and nearly all of it was done before the German and French Schools had elaborated their schemes of skull measurements"
| 36243239 | https://en.wikipedia.org/wiki?curid=36243239 |
Natural_sciences | William Bean (geologist)
William Bean (1787–1866) was an English geologist and conchologist. He was a pioneer of Yorkshire geology. In 1859 he sold his collection of over 15,000 fossils (mostly from localities around Scarborough). The majority of his collection was purchased by the British Museum and the Yorkshire Philosophical Society.
Bean described several new species of Mollusca, including the whelk "Beringius turtoni", named in honor of William Turton. Bean was associated with the "Magazine of Natural History", and was a friend of Joshua Alder and Albany Hancock.
| 36246497 | https://en.wikipedia.org/wiki?curid=36246497 |
Natural_sciences | Robert Damon
Robert Damon (1814 – 4 May 1889) was an English conchologist and geologist.
Damon was at first a hosier and glover but with his son Robert Ferris Damon (1845–1929) he established a dealership in natural history specimens in Weymouth. The company supplied museums throughout North and South America, Australia and Europe with much Dorset geological material from the late 1840s to 1914. In 1860 Damon wrote "Geology of Weymouth and the Isles of Portland; with Notes on the Natural History of the Coast and Neighbourhood" which includes a map of the district, geological sections, plates of fossils, and coast views, in 1884 a second edition with archaeological notes was published. He also wrote (and published himself in 1857) "A catalogue of the shells of Great Britain and Ireland with their synonyms and authorities".
Damon died aged 75 at his museum in Weymouth from heart disease.
The species "Amoria damonii" Gray, and "Paramelania damoni" were named in his honor.
| 36247158 | https://en.wikipedia.org/wiki?curid=36247158 |
Natural_sciences | Anton Moro
Anton Lazzaro Moro (1687 in San Vito al Tagliamento – 1764) was an Italian abbot, geologist and naturalist. He was one of the leading advocates of plutonism in the early debate that confronted plutonism to neptunism, making him described by some authors as an ultraplutonist. He was the first to discriminate sedimentary rocks from volcanic ones by studying the rocks of volcanic islands. In his study of the crustaceans, he discovered fossils petrified in mountains that led him to deduce those rocks were once buried in the sea.
| 36291124 | https://en.wikipedia.org/wiki?curid=36291124 |
Natural_sciences | Theory of the Earth
Theory of the Earth was a publication by James Hutton which laid the foundations for geology. In it he showed that the Earth is the product of natural forces. What could be seen happening today, over long periods of time, could produce what we see in the rocks. It also hypothesized that the age of the Earth was much older than what biblical literalists claim. This idea, uniformitarianism, was used by Charles Lyell in his work, and Lyell's textbook was an important influence on Charles Darwin. The work was first published in 1788 by the Royal Society of Edinburgh, and later in 1795 as two book volumes.
Hutton recognized that rocks record the evidence of the past action of processes which still operate today. He also anticipated natural selection, as follows: "Those which depart most from the best adapted constitution, will be the most liable to perish, while, on the other hand, those organised bodies, which most approach to the best constitution for the present circumstances, will be best adapted to continue, in preserving themselves and multiplying the individuals of their race".
Hutton's prose hindered his theories. They were not taken seriously until 1802, when Edinburgh University mathematics professor John Playfair restated Hutton's geological ideas in clearer English. However, he left out Hutton's thoughts on evolution. Charles Lyell in the 1830s popularised the idea of an infinitely repeating cycle (of the erosion of rocks and the building up of sediment). Lyell believed in gradual change, and thought even Hutton gave too much credit to catastrophic changes.
Hutton's work was published in different forms and stages:
| 36294056 | https://en.wikipedia.org/wiki?curid=36294056 |
Natural_sciences | ViroMed
ViroMed Co., Ltd. (VM BioPharma in the US) is a biotechnology company located in Seoul, Korea with US presence in Atlanta and the San Francisco Bay Area. The company works on DNA and protein-based therapeutics for various life-threatening diseases, along with herbal-based medicines, and nutraceuticals. ViroMed has five main products in its pipeline targeting cardiovascular disease, cancer, and immune-related disorder, with clinical trials in the US, Korea, and China. The company has established partnerships with global firms including Johnson & Johnson (Biologics Delivery Systems Group of Cordis Corp., USA), SBI Biotech (Japan), and Green Cross (Korea). The company also conducts preclinical developmental studies in the aspects of toxicology, efficacy and pharmacokinetics. Phase I and II clinical studies are also carried out.
ViroMed Co., Ltd. (ViroMed) was established in 1996 as ViroMedica Pacific, Inc., later changed to ViroMed in 1999. The company is headquartered in Seoul, Korea with US presence in Atlanta, GA. ViroMed has been listed on KOSDAQ (084990) since 2006. As of Jan. 6th, 2017, the total number of issued shares is 15,956,260 with market capitalization approximately at US$1.6 billion.
VM202 is a DNA-based medicine designed to express two isoforms of hepatocyte growth factor (HGF), a protein known to induce the formation of new blood vessels and the growth of damaged nerve cells. Currently, VM202 is being tested for 4 major cardiovascular or neurological diseases. In all cases, VM202 is delivered by simple intramuscular injection around the affected site. A phase III study for painful diabetic peripheral neuropathy (VM202-DPN) has been successfully initiated in the US in 2016. As of May 2017, over 160 have been randomized in the US among whom over 140 patients have completed their first injections at 21 clinical sites. A phase III study for chronic, non-healing foot ulcer associated with diabetes (VM202-PAD) has received approval from the US FDA and will have patient enrollment in 2017 in the US. After successful phase I trial for coronary artery disease (VM202-CAD), a phase II study is planned as IRB review in clinical sites is currently underway in Korea. VM202 has also successfully completed a phase I/II for amyotrophic lateral sclerosis (VM202-ALS), also known as Lou Gehrig's disease, which received orphan drug status and fast track designation from the US FDA. Its phase II IND has been approved by the US FDA in 2016.
In 2004, ViroMed transferred VM202 and associated technologies to Beijing Northland Biotech for commercialization purposes; in 2018, VM202 continued on to phase III clinical trials in China.
VM206 is a therapeutic cancer vaccine targeting HER2/neu positive breast or ovarian cancer. Her2/neu is over-expressed in about 30% of breast cancers and is strongly associated with poor prognosis. VM206 can elicit an immune response to HER2/neu, which is hoped to reduce the growth and recurrence rate of breast or ovarian cancer.
VM501 is a re-engineered form of interleukin 11 (IL-11) targeting chemotherapy-induced thrombocytopenia (CIT) that is said to be less toxic than the existing FDA-approved drugs.
According to its website, the company is involved in the following clinical trials:
| 36294209 | https://en.wikipedia.org/wiki?curid=36294209 |
Natural_sciences | Induced stem cells
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – iMSC, also called an induced multipotent progenitor cell – iMPC) or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.
Three techniques are widely recognized:
In 1895 Thomas Morgan removed one of a frog's two blastomeres and found that amphibians are able to form whole embryos from the remaining part. This meant that the cells can change their differentiation pathway. In 1924 Spemann and Mangold demonstrated the key importance of cell–cell inductions during animal development. The reversible transformation of cells of one differentiated cell type to another is called metaplasia. This transition can be a part of the normal maturation process, or caused by an inducement.
One example is the transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace cells not suitable to new conditions with more suitable new cells. In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation.
The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, "in vivo" or "in vitro", uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.
Some types of mature, specialized adult cells can naturally revert to stem cells. For example, "chief" cells express the stem cell marker Troy. While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent "reserve" stem cells. Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo.
After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand.
A variety of nontumorigenic stem cells display the ability to generate multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo.
Other well-documented examples of transdifferentiation and their significance in development and regeneration were described in detail.
Induced totipotent cells can be obtained by reprogramming somatic cells with somatic-cell nuclear transfer (SCNT). The process involves sucking out the nucleus of a somatic (body) cell and injecting it into an oocyte that has had its nucleus removed
Using an approach based on the protocol outlined by Tachibana et al., hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells. Such reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. Unfortunately, the cells generated by this technology, potentially are not completely protected from the immune system of the patient (donor of nuclei), because they have the same mitochondrial DNA, as a donor of oocytes, instead of the patients mitochondrial DNA. This reduces their value as a source for autologous stem cell transplantation therapy, as for the present, it is not clear whether it can induce an immune response of the patient upon treatment.
Induced androgenetic haploid embryonic stem cells can be used instead of sperm for cloning. These cells, synchronized in M phase and injected into the oocyte can produce viable offspring.
These developments, together with data on the possibility of unlimited oocytes from mitotically active reproductive stem cells, offer the possibility of industrial production of transgenic farm animals. Repeated recloning of viable mice through a SCNT method that includes a histone deacetylase inhibitor, trichostatin, added to the cell culture medium, show that it may be possible to reclone animals indefinitely with no visible accumulation of reprogramming or genomic errors However, research into technologies to develop sperm and egg cells from stem cells raises bioethical issues.
Such technologies may also have far-reaching clinical applications for overcoming cytoplasmic defects in human oocytes. For example, the technology could prevent inherited mitochondrial disease from passing to future generations. Mitochondrial genetic material is passed from mother to child. Mutations can cause diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and other neurological diseases. The nucleus from one human egg has been transferred to another, including its mitochondria, creating a cell that could be regarded as having two mothers. The eggs were then fertilised and the resulting embryonic stem cells carried the swapped mitochondrial DNA.
As evidence that the technique is safe author of this method points to the existence of the healthy monkeys that are now more than four years old – and are the product of mitochondrial transplants across different genetic backgrounds.
In late-generation telomerase-deficient (Terc−/−) mice, SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming.
Other cloning and totipotent transformation achievements have been described.
Recently some researchers succeeded to get the totipotent cells without the aid of SCNT. Totipotent cells were obtained using the epigenetic factors such as oocyte germinal isoform of histone.
Reprogramming in vivo, by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice, confers totipotency features. Intraperitoneal injection of such in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic (trophectodermal) markers.
The developmental potential of mouse pluripotent stem cells to yield both embryonic and extra-embryonic lineages also can be expanded by microRNA miR-34a deficiency leading to strong induction of endogenous retroviruses MuERV-L (MERVL).
iPSc were first obtained in the form of transplantable teratocarcinoma induced by grafts taken from mouse embryos. Teratocarcinoma formed from somatic cells. Genetically mosaic mice were obtained from malignant teratocarcinoma cells, confirming the cells' pluripotency. It turned out that teratocarcinoma cells are able to maintain a culture of pluripotent embryonic stem cell in an undifferentiated state, by supplying the culture medium with various factors. In the 1980s, it became clear that transplanting pluripotent/embryonic stem cells into the body of adult mammals, usually leads to the formation of teratomas, which can then turn into a malignant tumor teratocarcinoma. However, putting teratocarcinoma cells into the embryo at the blastocyst stage, caused them to become incorporated in the inner cell mass and often produced a normal chimeric (i.e. composed of cells from different organisms) animal. This indicated that the cause of the teratoma is a dissonance - mutual miscommunication between young donor cells and surrounding adult cells (the recipient's so-called "niche").
In August 2006, Japanese researchers circumvented the need for an oocyte, as in SCNT. By reprograming mouse embryonic fibroblasts into pluripotent stem cells via the ectopic expression of four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc, they proved that the overexpression of a small number of factors can push the cell to transition to a new stable state that is associated with changes in the activity of thousands of genes.
Reprogramming mechanisms are thus linked, rather than independent and are centered on a small number of genes.
IPSC properties are very similar to ESCs. iPSCs have been shown to support the development of all-iPSC mice using a tetraploid (4n) embryo, the most stringent assay for developmental potential. However, some genetically normal iPSCs failed to produce all-iPSC mice because of aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster. A team headed by Hans Schöler (who discovered the Oct4 gene back in 1989) showed that Oct4 overexpression drives massive off-target gene activation during reprogramming deteriorating the quality of iPSCs. Comparing to OSKM (Oct4, Sox2, Klf4 and c-Myc)that show abnormal imprinting and differentiation patterns, SKM (Sox2, Klf4 and c-Myc) reprogramming generates iPSCs with high developmental potential (nearly 20-fold higher than that of OSKM) equivalent to embryonic stem cell, as determined by their ability to generate all-iPSC mice through tetraploid embryo complementation
An important advantage of iPSC over ESC is that they can be derived from adult cells, rather than from embryos. Therefore, it became possible to obtain iPSC from adult and even elderly patients.
Reprogramming somatic cells to iPSC leads to rejuvenation. It was found that reprogramming leads to telomere lengthening and subsequent shortening after their differentiation back into fibroblast-like derivatives. Thus, reprogramming leads to the restoration of embryonic telomere length, and hence increases the potential number of cell divisions otherwise limited by the Hayflick limit.
However, because of the dissonance between rejuvenated cells and the surrounding niche of the recipient's older cells, the injection of his own iPSC usually leads to an immune response, which can be used for medical purposes, or the formation of tumors such as teratoma. The reason has been hypothesized to be that some cells differentiated from ESC and iPSC in vivo continue to synthesize embryonic protein isoforms. So, the immune system might detect and attack cells that are not cooperating properly.
A small molecule called MitoBloCK-6 can force the pluripotent stem cells to die by triggering apoptosis (via cytochrome c release across the mitochondrial outer membrane) in human pluripotent stem cells, but not in differentiated cells. Shortly after differentiation, daughter cells became resistant to death. When MitoBloCK-6 was introduced to differentiated cell lines, the cells remained healthy. The key to their survival, was hypothesized to be due to the changes undergone by pluripotent stem cell mitochondria in the process of cell differentiation. This ability of MitoBloCK-6 to separate the pluripotent and differentiated cell lines has the potential to reduce the risk of teratomas and other problems in regenerative medicine.
In 2012 other small molecules (selective cytotoxic inhibitors of human pluripotent stem cells – hPSCs) were identified that prevented human pluripotent stem cells from forming teratomas in mice. The most potent and selective compound of them (PluriSIn #1) inhibits stearoyl-coA desaturase (the key enzyme in oleic acid biosynthesis), which finally results in apoptosis. With the help of this molecule the undifferentiated cells can be selectively removed from culture. An efficient strategy to selectively eliminate pluripotent cells with teratoma potential is targeting pluripotent stem cell-specific antiapoptotic factor(s) (i.e., survivin or Bcl10). A single treatment with chemical survivin inhibitors (e.g., quercetin or YM155) can induce selective and complete cell death of undifferentiated hPSCs and is claimed to be sufficient to prevent teratoma formation after transplantation. However, it is unlikely that any kind of preliminary clearance, is able to secure the replanting iPSC or ESC. After the selective removal of pluripotent cells, they re-emerge quickly by reverting differentiated cells into stem cells, which leads to tumors. This may be due to the disorder of let-7 regulation of its target Nr6a1 (also known as Germ cell nuclear factor - GCNF), an embryonic transcriptional repressor of pluripotency genes that regulates gene expression in adult fibroblasts following micro-RNA miRNA loss.
Teratoma formation by pluripotent stem cells may be caused by low activity of PTEN enzyme, reported to promote the survival of a small population (0.1–5% of total population) of highly tumorigenic, aggressive, teratoma-initiating embryonic-like carcinoma cells during differentiation. The survival of these teratoma-initiating cells is associated with failed repression of Nanog as well as a propensity for increased glucose and cholesterol metabolism. These teratoma-initiating cells also expressed a lower ratio of p53/p21 when compared to non-tumorigenic cells.
In connection with the above safety problems, the use iPSC for cell therapy is still limited. However, they can be used for a variety of other purposes - including the modeling of disease, screening (selective selection) of drugs, toxicity testing of various drugs.
The tissue grown from iPSCs, placed in the "chimeric" embryos in the early stages of mouse development, practically do not cause an immune response (after the embryos have grown into adult mice) and are suitable for autologous transplantation
At the same time, full reprogramming of adult cells in vivo within tissues by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs. Furthermore, partial reprogramming of cells toward pluripotency in vivo in mice demonstrates that incomplete reprogramming entails epigenetic changes (failed repression of Polycomb targets and altered DNA methylation) in cells that drive cancer development.
By using solely small molecules, Deng Hongkui and colleagues demonstrated that endogenous "master genes" are enough for cell fate reprogramming. They induced a pluripotent state in adult cells from mice using seven small-molecule compounds.
The effectiveness of the method is quite high: it was able to convert 0.02% of the adult tissue cells into iPSCs, which is comparable to the gene insertion conversion rate.
The authors note that the mice generated from CiPSCs were "100% viable and apparently healthy for up to 6 months". So, this chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.
In 2015 a robust chemical reprogramming system was established with a yield up to 1,000-fold greater than that of the previously reported protocol. So, chemical reprogramming became a promising approach to manipulate cell fates.
The fact that human iPSCs capable of forming teratomas not only in humans but also in some animal body, in particular in mice or pigs, allowed to develop a method for differentiation of iPSCs in vivo. For this purpose, iPSCs with an agent for inducing differentiation into target cells are injected to genetically modified pig or mouse that has suppressed immune system activation on human cells.
The formed teratoma is cut out and used for the isolation of the necessary differentiated human cells by means of monoclonal antibody to tissue-specific markers on the surface of these cells. This method has been successfully used for the production of functional myeloid, erythroid and lymphoid human cells suitable for transplantation (yet only to mice).
Mice engrafted with human iPSC teratoma-derived hematopoietic cells produced human B and T cells capable of functional immune responses. These results offer hope that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation and drug screening applications.
Using MitoBloCK-6 and/or PluriSIn # 1 the differentiated progenitor cells can be further purified from teratoma forming pluripotent cells. The fact, that the differentiation takes place even in the teratoma niche, offers hope that the resulting cells are sufficiently stable to stimuli able to cause their transition back to the dedifferentiated (pluripotent) state and therefore safe. A similar in vivo differentiation system, yielding engraftable hematopoietic stem cells from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis, was described by Suzuki et al. They noted that neither leukemia nor tumors were observed in recipients after intravenous injection of iPSC-derived hematopoietic stem cells into irradiated recipients. Moreover, this injection resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Such system provides a useful tool for practical application of iPSCs in the treatment of hematologic and immunologic diseases.
For further development of this method animal in which is grown the human cell graft, for example mouse, must have so modified genome that all its cells express and have on its surface human SIRPα.
To prevent rejection after transplantation to the patient of the allogenic organ or tissue, grown from the pluripotent stem cells in vivo in the animal, these cells should express two molecules: CTLA4-Ig, which disrupts T cell costimulatory pathways and PD-L1, which activates T cell inhibitory pathway.
See also: .
In the near-future, clinical trials designed to demonstrate the safety of the use of iPSCs for cell therapy of the people with age-related macular degeneration, a disease causing blindness through retina damaging, will begin. There are several articles describing methods for producing retinal cells from iPSCs
and how to use them for cell therapy. Reports of iPSC-derived retinal pigmented epithelium transplantation showed enhanced
visual-guided behaviors of experimental animals for 6 weeks after transplantation. However, clinical trials have been successful: ten patients suffering from retinitis pigmentosa have had their eyesight restored – including a woman who had only 17 percent of her vision left.
Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. So there is an urgent need for effective cell therapy and lung tissue engineering.
Several protocols have been developed for generation of the most cell types of the respiratory system, which may be useful for deriving patient-specific therapeutic cells.
Some lines of iPSCs have the potentiality to differentiate into male germ cells and oocyte-like cells in an appropriate niche (by culturing in retinoic acid and porcine follicular fluid differentiation medium or seminiferous tubule transplantation). Moreover, iPSC transplantation make a contribution to repairing the testis of infertile mice, demonstrating the potentiality of gamete derivation from iPSCs in vivo and in vitro.
The risk of cancer and tumors creates the need to develop methods for safer cell lines suitable for clinical use. An alternative approach is so-called "direct reprogramming" – transdifferentiation of cells without passing through the pluripotent state. The basis for this approach was that 5-azacytidine – a DNA demethylation reagent – can cause the formation of myogenic, chondrogenic and adipogeni clones in the immortal cell line of mouse embryonic fibroblasts and that the activation of a single gene, later named MyoD1, is sufficient for such reprogramming. Compared with iPSC whose reprogramming requires at least two weeks, the formation of induced progenitor cells sometimes occurs within a few days and the efficiency of reprogramming is usually many times higher. This reprogramming does not always require cell division. The cells resulting from such reprogramming are more suitable for cell therapy because they do not form teratomas.
For example, Chandrakanthan et al., & Pimanda describe the generation of tissue-regenerative multipotent stem cells (iMS cells) by treating mature bone and fat cells transiently with a growth factor (platelet-derived growth factor–AB (PDGF-AB)) and 5-Azacytidine. These authors claim that: "Unlike primary mesenchymal stem cells, which are used with little objective evidence in clinical practice to promote tissue repair, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner without forming tumors" and so "has significant scope for application in tissue regeneration."
Originally only early embryonic cells could be coaxed into changing their identity. Mature cells are resistant to changing their identity once they've committed to a specific kind. However, brief expression of a single transcription factor, the ELT-7 GATA factor, can convert the identity of fully differentiated, specialized non-endodermal cells of the pharynx into fully differentiated intestinal cells in intact larvae and adult roundworm "Caenorhabditis elegans" with no requirement for a dedifferentiated intermediate.
The cell fate can be effectively manipulated by epigenome editing. In particular, by directly activating of specific endogenous gene expression with CRISPR-mediated activator. When dCas9 (that has been modified so that it no longer cuts DNA, but still can be guided to specific sequences and to bind to them) is combined with transcription activators, it can precisely manipulate endogenous gene expression. Using this method, Wei et al., enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus directly converted mouse embryonic stem cells into two extraembryonic lineages, i.e., typical trophoblast stem cells and extraembryonic endoderm cells. An analogous approach was used to induce activation of the endogenous Brn2, Ascl1, and Myt1l genes to convert mouse embryonic fibroblasts to induced neuronal cells. Thus, transcriptional activation and epigenetic remodeling of endogenous master transcription factors are sufficient for conversion between cell types. The rapid and sustained activation of endogenous genes in their native chromatin context by this approach may facilitate reprogramming with transient methods that avoid genomic integration and provides a new strategy for overcoming epigenetic barriers to cell fate specification.
Another way of reprogramming is the simulation of the processes that occur during amphibian limb regeneration. In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates into limb tissue. However, sequential small molecule treatment of the muscle fiber with myoseverin, reversine (the aurora B kinase inhibitor) and some other chemicals: BIO (glycogen synthase-3 kinase inhibitor), lysophosphatidic acid (pleiotropic activator of G-protein-coupled receptors), SB203580 (p38 MAP kinase inhibitor), or SQ22536 (adenylyl cyclase inhibitor) causes the formation of new muscle cell types as well as other cell types such as precursors to fat, bone and nervous system cells.
The researchers discovered that GCSF-mimicking antibody can activate a growth-stimulating receptor on marrow cells in a way that induces marrow stem cells that normally develop into white blood cells to become neural progenitor cells. The technique enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect.
The human gastrointestinal tract is colonized by a vast community of symbionts and commensals. The researchers demonstrate the phenomenon of somatic cell reprograming by bacteria and generation of multipotential cells from adult human dermal fibroblast cells by incorporating Lactic acid bacteria This cellular transdifferentiation is caused by ribosomes and "can occur via donor bacteria that are swallowed and digested by host cells, which may induce ribosomal stress and stimulate cellular developmental plasticity."
Schlegel and Liu demonstrated that the combination of feeder cells and a Rho kinase inhibitor (Y-27632) induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro. This process occurs without the need for transduction of exogenous viral or cellular genes. These cells have been termed "Conditionally Reprogrammed Cells (CRC)". The induction of CRCs is rapid and results from reprogramming of the entire cell population. CRCs do not express high levels of proteins characteristic of iPSCs or embryonic stem cells (ESCs) (e.g., Sox2, Oct4, Nanog, or Klf4). This induction of CRCs is reversible and removal of Y-27632 and feeders allows the cells to differentiate normally. CRC technology can generate 2 cells in 5 to 6 days from needle biopsies and can generate cultures from cryopreserved tissue and from fewer than four viable cells. CRCs retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors.
The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking. Using CRC technology, researchers were able to identify an effective therapy for a patient with a rare type of lung tumor. Engleman's group describes a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance using CRC system. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host. While initial studies revealed that co-culturing epithelial cells with Swiss 3T3 cells J2 was essential for CRC induction, with transwell culture plates, physical contact between feeders and epithelial cells is not required for inducing CRCs and more importantly that irradiation of the feeder cells is required for this induction. Consistent with the transwell experiments, conditioned medium induces and maintains CRCs, which is accompanied by a concomitant increase of cellular telomerase activity. The activity of the conditioned medium correlates directly with radiation-induced feeder cell apoptosis. Thus, conditional reprogramming of epithelial cells is mediated by a combination of Y-27632 and a soluble factor(s) released by apoptotic feeder cells.
Riegel et al. demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu–induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs). Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+ and ESA+ (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.
A different approach to CRC is to inhibit CD47 – a membrane protein that is the thrombospondin-1 receptor. Loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells in vitro and in vivo. Thrombospondin-1 is a key environmental signal that inhibits stem cell self-renewal via CD47. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors. In vivo blockade of CD47 using an antisense morpholino increases survival of mice exposed to lethal total body irradiation due to increased proliferative capacity of bone marrow-derived cells and radioprotection of radiosensitive gastrointestinal tissues.
Differentiated macrophages can self-renew in tissues and expand long-term in culture. Under certain conditions macrophages can divide without losing features they have acquired while specializing into immune cells – which is usually not possible with differentiated cells. The macrophages achieve this by activating a gene network similar to one found in embryonic stem cells. Single-cell analysis revealed that, "in vivo", proliferating macrophages can derepress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. This happened when concentrations of two transcription factors named MafB and c-Maf were naturally low or were inhibited for a short time. Genetic manipulations that turned off MafB and c-Maf in the macrophages caused the cells to start a self-renewal program. The similar network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers.
Hence macrophages isolated from MafB- and c-Maf-double deficient mice divide indefinitely; the self-renewal depends on c-Myc and Klf4.
Indirect lineage conversion is a reprogramming methodology in which somatic cells transition through a plastic intermediate state of partially reprogrammed cells (pre-iPSC), induced by brief exposure to reprogramming factors, followed by differentiation in a specially developed chemical environment (artificial niche).
This method could be both more efficient and safer, since it does not seem to produce tumors or other undesirable genetic changes and results in much greater yield than other methods. However, the safety of these cells remains questionable. Since lineage conversion from pre-iPSC relies on the use of iPSC reprogramming conditions, a fraction of the cells could acquire pluripotent properties if they do not stop the de-differentation process in vitro or due to further de-differentiation in vivo.
A common feature of pluripotent stem cells is the specific nature of protein glycosylation of their outer membrane. That distinguishes them from most nonpluripotent cells, although not white blood cells. The glycans on the stem cell surface respond rapidly to alterations in cellular state and signaling and are therefore ideal for identifying even minor changes in cell populations. Many stem cell markers are based on cell surface glycan epitopes including the widely used markers SSEA-3, SSEA-4, Tra 1-60 and Tra 1-81. Suila Heli et al. speculate that in human stem cells extracellular O-GlcNAc and extracellular O-LacNAc, play a crucial role in the fine tuning of Notch signaling pathway - a highly conserved cell signaling system, that regulates cell fate specification, differentiation, left–right asymmetry, apoptosis, somitogenesis, angiogenesis and plays a key role in stem cell proliferation (reviewed by Perdigoto and Bardin and Jafar-Nejad et al.)
Changes in outer membrane protein glycosylation are markers of cell states connected in some way with pluripotency and differentiation. The glycosylation change is apparently not just the result of the initialization of gene expression, but perform as an important gene regulator involved in the acquisition and maintenance of the undifferentiated state.
For example, activation of glycoprotein ACA, linking glycosylphosphatidylinositol on the surface of the progenitor cells in human peripheral blood, induces increased expression of genes Wnt, Notch-1, BMI1 and HOXB4 through a signaling cascade PI3K/Akt/mTor/PTEN and promotes the formation of a self-renewing population of hematopoietic stem cells.
Furthermore, dedifferentiation of progenitor cells induced by ACA-dependent signaling pathway leads to ACA-induced pluripotent stem cells, capable of differentiating in vitro into cells of all three germ layers.
The study of lectins' ability to maintain a culture of pluripotent human stem cells has led to the discovery of lectin Erythrina crista-galli (ECA), which can serve as a simple and highly effective matrix for the cultivation of human pluripotent stem cells.
Cell adhesion protein E-cadherin is indispensable for a robust pluripotent phenotype. During reprogramming for iPS cell generation, N-cadherin can replace function of E-cadherin. These functions of cadherins are not directly related to adhesion because sphere morphology helps maintaining the "stemness" of stem cells. Moreover, sphere formation, due to forced growth of cells on a low attachment surface, sometimes induces reprogramming. For example, neural progenitor cells can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.
Physical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells' epigenetic state. Specifically, "decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5) – a subunit of H3 methyltranferase – by microgrooved surfaces lead to increased histone H3 acetylation and methylation". Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state.
Substrate rigidity is an important biophysical cue influencing neural induction and subtype specification. For example, soft substrates promote neuroepithelial conversion while inhibiting neural crest differentiation of hESCs in a BMP4-dependent manner. Mechanistic studies revealed a multi-targeted mechanotransductive process involving mechanosensitive Smad phosphorylation and nucleocytoplasmic shuttling, regulated by rigidity-dependent Hippo/YAP activities and actomyosin cytoskeleton integrity and contractility.
Mouse embryonic stem cells (mESCs) undergo self-renewal in the presence of the cytokine leukemia inhibitory factor (LIF). Following LIF withdrawal, mESCs differentiate, accompanied by an increase in cell–substratum adhesion and cell spreading. Restricted cell spreading in the absence of LIF by either culturing mESCs on chemically defined, weakly adhesive biosubstrates, or by manipulating the cytoskeleton allowed the cells to remain in an undifferentiated and pluripotent state. The effect of restricted cell spreading on mESC self-renewal is not mediated by increased intercellular adhesion, as inhibition of mESC adhesion using a function blocking anti E-cadherin antibody or siRNA does not promote differentiation.
Possible mechanisms of stem cell fate predetermination by physical interactions with the extracellular matrix have been described.
A new method has been developed that turns cells into stem cells faster and more efficiently by 'squeezing' them using 3D microenvironment stiffness and density of the surrounding gel. The technique can be applied to a large number of cells to produce stem cells for medical purposes on an industrial scale.
Cells involved in the reprogramming process change morphologically as the process proceeds. This results in physical difference in adhesive forces among cells. Substantial differences in 'adhesive signature' between pluripotent stem cells, partially reprogrammed cells, differentiated progeny and somatic cells allowed to develop separation process for isolation of pluripotent stem cells in microfluidic devices, which is:
Stem cells possess mechanical memory (they remember past physical signals) – with the Hippo signaling pathway factors: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) acting as an intracellular mechanical rheostat—that stores information from past physical environments and influences the cells' fate.
Stroke and many neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis need cell replacement therapy. The successful use of converted neural cells (cNs) in transplantations open a new avenue to treat such diseases. Nevertheless, induced neurons (iNs), directly converted from fibroblasts are terminally committed and exhibit very limited proliferative ability that may not provide enough autologous donor cells for transplantation. Self-renewing induced neural stem cells (iNSCs) provide additional advantages over iNs for both basic research and clinical applications.
For example, under specific growth conditions, mouse fibroblasts can be reprogrammed with a single factor, Sox2, to form iNSCs that self-renew in culture and after transplantation can survive and integrate without forming tumors in mouse brains. INSCs can be derived from adult human fibroblasts by non-viral techniques, thus offering a safe method for autologous transplantation or for the development of cell-based disease models.
Neural chemically induced progenitor cells (ciNPCs) can be generated from mouse tail-tip fibroblasts and human urinary somatic cells without introducing exogenous factors, but - by a chemical cocktail, namely VCR (V, VPA, an inhibitor of HDACs; C, CHIR99021, an inhibitor of GSK-3 kinases and R, RepSox, an inhibitor of TGF beta signaling pathways), under a physiological hypoxic condition. Alternative cocktails with inhibitors of histone deacetylation, glycogen synthase kinase and TGF-β pathways (where: sodium butyrate (NaB) or Trichostatin A (TSA) could replace VPA, Lithium chloride (LiCl) or lithium carbonate (Li2CO3) could substitute CHIR99021, or Repsox may be replaced with SB-431542 or Tranilast) show similar efficacies for ciNPC induction.
Zhang, et al., also report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components.
Multiple methods of direct transformation of somatic cells into induced neural stem cells have been described.
Proof of principle experiments demonstrate that it is possible to convert transplanted human fibroblasts and human astrocytes directly in the brain that are engineered to express inducible forms of neural reprogramming genes, into neurons, when reprogramming genes (Ascl1, Brn2a and Myt1l) are activated after transplantation using a drug.
Astrocytes – the most common neuroglial brain cells, which contribute to scar formation in response to injury – can be directly reprogrammed in vivo to become functional neurons that formed networks in mice without the need of cell transplantation. The researchers followed the mice for nearly a year to look for signs of tumor formation and reported finding none. The same researchers have turned scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons in the injured adult spinal cord.
Without myelin to insulate neurons, nerve signals quickly lose power. Diseases that attack myelin, such as multiple sclerosis, result in nerve signals that cannot propagate to nerve endings and as a consequence lead to cognitive, motor and sensory problems. Transplantation of oligodendrocyte precursor cells (OPCs), which can successfully create myelin sheaths around nerve cells, is a promising potential therapeutic response. Direct lineage conversion of mouse and rat fibroblasts into oligodendroglial cells provides a potential source of OPCs. Conversion by forced expression of both eight or of the three transcription factors Sox10, Olig2 and Zfp536, may provide such cells.
Cell-based in vivo therapies may provide a transformative approach to augment vascular and muscle growth and to prevent non-contractile scar formation by delivering transcription factors or microRNAs to the heart. Cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of cardiac core transcription factors ( GATA4, MEF2C, TBX5 and for improved reprogramming plus ESRRG, MESP1, Myocardin and ZFPM2) after coronary ligation. These results implicated therapies that can directly remuscularize the heart without cell transplantation. However, the efficiency of such reprogramming turned out to be very low and the phenotype of received cardiomyocyte-like cells does not resemble those of a mature normal cardiomyocyte. Furthermore, transplantation of cardiac transcription factors into injured murine hearts resulted in poor cell survival and minimal expression of cardiac genes.
Meanwhile, advances in the methods of obtaining cardiac myocytes in vitro occurred. Efficient cardiac differentiation of human iPS cells gave rise to progenitors that were retained within infarcted rat hearts and reduced remodeling of the heart after ischemic damage.
The team of scientists, who were led by Sheng Ding, used a cocktail of nine chemicals (9C) for transdifferentiation of human skin cells into beating heart cells. With this method, more than 97% of the cells began beating, a characteristic of fully developed, healthy heart cells. The chemically induced cardiomyocyte-like cells (ciCMs) uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to ciCMs and developed into healthy-looking heart muscle cells within the organ. This chemical reprogramming approach, after further optimization, may offer an easy way to provide the cues that induce heart muscle to regenerate locally.
In another study, ischemic cardiomyopathy in the murine infarction model was targeted by iPS cell transplantation. It synchronized failing ventricles, offering a regenerative strategy to achieve resynchronization and protection from decompensation by dint of improved left ventricular conduction and contractility, reduced scarring and reversal of structural remodelling.
One protocol generated populations of up to 98% cardiomyocytes from hPSCs simply by modulating the canonical Wnt signaling pathway at defined time points in during differentiation, using readily accessible small molecule compounds.
Discovery of the mechanisms controlling the formation of cardiomyocytes led to the development of the drug ITD-1, which effectively clears the cell surface from TGF-β receptor type II and selectively inhibits intracellular TGF-β signaling. It thus selectively enhances the differentiation of uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and endothelial cells.
One project seeded decellularized mouse hearts with human iPSC-derived multipotential cardiovascular progenitor cells. The introduced cells migrated, proliferated and differentiated in situ into cardiomyocytes, smooth muscle cells and endothelial cells to reconstruct the hearts. In addition, the heart's extracellular matrix (the substrate of heart scaffold) signalled the human cells into becoming the specialised cells needed for proper heart function. After 20 days of perfusion with growth factors, the engineered heart tissues started to beat again and were responsive to drugs.
Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) "in situ" represents a promising strategy for cardiac regeneration. Mice exposed "in vivo", to three cardiac transcription factors GMT (Gata4, Mef2c, Tbx5) and the small-molecules: SB-431542 (the transforming growth factor (TGF)-β inhibitor), and XAV939 (the WNT inhibitor) for 2 weeks after myocardial infarction showed significantly improved reprogramming (reprogramming efficiency increased eight-fold) and cardiac function compared to those exposed to only GMT.
See also: review
The elderly often suffer from progressive muscle weakness and regenerative failure owing in part to elevated activity of the p38α and p38β mitogen-activated kinase pathway in senescent skeletal muscle stem cells. Subjecting such stem cells to transient inhibition of p38α and p38β in conjunction with culture on soft hydrogel substrates rapidly expands and rejuvenates them that result in the return of their strength.
In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a (also called Cdkn2a).
On injury, these cells fail to activate and expand, even in a youthful environment. p16INK4a silencing in geriatric satellite cells restores quiescence and muscle regenerative functions.
Myogenic progenitors for potential use in disease modeling or cell-based therapies targeting skeletal muscle could also be generated directly from induced pluripotent stem cells using free-floating spherical culture (EZ spheres) in a culture medium supplemented with high concentrations (100 ng/ml) of fibroblast growth factor-2 (FGF-2) and epidermal growth factor.
Unlike current protocols for deriving hepatocytes from human fibroblasts, Saiyong Zhu et al., (2014) did not generate iPSCs but, using small molecules, cut short reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) state from which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) were efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte function similar to those of human primary adult hepatocytes. iMPC-Heps did not form tumours, most probably because they never entered a pluripotent state.
These results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy.
Cocktail of small molecules, Y-27632, A-83-01 (a TGFβ kinase/activin receptor like kinase (ALK5) inhibitor), and CHIR99021 (potent inhibitor of GSK-3), can convert rat and mouse mature hepatocytes in vitro into proliferative bipotent cells – CLiPs (chemically induced liver progenitors). CLiPs can differentiate into both mature hepatocytes and biliary epithelial cells that can form functional ductal structures. In long-term culture CLiPs did not lose their proliferative capacity and their hepatic differentiation ability, and can repopulate chronically injured liver tissue.
Complications of Diabetes mellitus such as cardiovascular diseases, retinopathy, neuropathy, nephropathy and peripheral circulatory diseases depend on sugar dysregulation due to lack of insulin from pancreatic beta cells and can be lethal if they are not treated. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs).
Unfortunately, human PSC-derived insulin-expressing cells resemble human fetal β cells rather than adult β cells. In contrast to adult β cells, fetal β cells seem functionally immature, as indicated by increased basal glucose secretion and lack of glucose stimulation and confirmed by RNA-seq of whose transcripts.
An alternative strategy is the conversion of fibroblasts towards distinct endodermal progenitor cell populations and, using cocktails of signalling factors, successful differentiation of these endodermal progenitor cells into functional beta-like cells both in vitro and in vivo.
Overexpression of the three transcription factors, PDX1 (required for pancreatic bud outgrowth and beta-cell maturation), NGN3 (required for endocrine precursor cell formation) and MAFA (for beta-cell maturation) combination (called PNM) can lead to the transformation of some cell types into a beta cell-like state.
An accessible and abundant source of functional insulin-producing cells is intestine. PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into β-like cells possibly acceptable for transplantation.
Adult proximal tubule cells were directly transcriptionally reprogrammed to nephron progenitors of the embryonic kidney, using a pool of six genes of instructive transcription factors (SIX1, SIX2, OSR1, Eyes absent homolog 1(EYA1), Homeobox A11 (HOXA11) and Snail homolog 2 (SNAI2)) that activated genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule cell line.
The generation of such cells may lead to cellular therapies for adult renal disease. Embryonic kidney organoids placed into adult rat kidneys can undergo onward development and vascular development.
As blood vessels age, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including myocardial infarction, ischemic stroke and atherosclerosis of arteries supplying the heart, brain and lower extremities. So, an important goal is to stimulate vascular growth for the collateral circulation to prevent the exacerbation of these diseases. Induced Vascular Progenitor Cells (iVPCs) are useful for cell-based therapy designed to stimulate coronary collateral growth. They were generated by partially reprogramming endothelial cells. The vascular commitment of iVPCs is related to the epigenetic memory of endothelial cells, which engenders them as cellular components of growing blood vessels. That is why, when iVPCs were implanted into myocardium, they engrafted in blood vessels and increased coronary collateral flow better than iPSCs, mesenchymal stem cells, or native endothelial cells.
Ex vivo genetic modification can be an effective strategy to enhance stem cell function. For example, cellular therapy employing genetic modification with Pim-1 kinase (a downstream effector of Akt, which positively regulates neovasculogenesis) of bone marrow–derived cells or human cardiac progenitor cells, isolated from failing myocardium results in durability of repair, together with the improvement of functional parameters of myocardial hemodynamic performance.
Stem cells extracted from fat tissue after liposuction may be coaxed into becoming progenitor smooth muscle cells (iPVSMCs) found in arteries and veins.
The 2D culture system of human iPS cells<ref name="doi10.1038/nbt1287"></ref> in conjunction with triple marker selection (CD34 (a surface glycophosphoprotein expressed on developmentally early embryonic fibroblasts), NP1 (receptor – neuropilin 1) and KDR (kinase insert domain-containing receptor)) for the isolation of vasculogenic precursor cells from human iPSC, generated endothelial cells that, after transplantation, formed stable, functional mouse blood vessels in vivo, lasting for 280 days.<ref name="doi10.1073/pnas.1310675110"></ref>
To treat infarction, it is important to prevent the formation of fibrotic scar tissue. This can be achieved in vivo by transient application of paracrine factors that redirect native heart progenitor stem cell contributions from scar tissue to cardiovascular tissue. For example, in a mouse myocardial infarction model, a single intramyocardial injection of human vascular endothelial growth factor A mRNA (VEGF-A modRNA), modified to escape the body's normal defense system, results in long-term improvement of heart function due to mobilization and redirection of epicardial progenitor cells toward cardiovascular cell types.<ref name="doi10.1038/nbt.2682"></ref>
RBC transfusion is necessary for many patients. However, to date the supply of RBCs remains labile. In addition, transfusion risks infectious disease transmission. A large supply of safe RBCs generated in vitro would help to address this issue. Ex vivo erythroid cell generation may provide alternative transfusion products to meet present and future clinical requirements. Red blood cells (RBC)s generated in vitro from mobilized CD34 positive cells have normal survival when transfused into an autologous recipient. RBC produced in vitro contained exclusively fetal hemoglobin (HbF), which rescues the functionality of these RBCs. In vivo the switch of fetal to adult hemoglobin was observed after infusion of nucleated erythroid precursors derived from iPSCs. Although RBCs do not have nuclei and therefore can not form a tumor, their immediate erythroblasts precursors have nuclei. The terminal maturation of erythroblasts into functional RBCs requires a complex remodeling process that ends with extrusion of the nucleus and the formation of an enucleated RBC. Cell reprogramming often disrupts enucleation. Transfusion of in vitro-generated RBCs or erythroblasts does not sufficiently protect against tumor formation.
The aryl hydrocarbon receptor (AhR) pathway (which has been shown to be involved in the promotion of cancer cell development) plays an important role in normal blood cell development. AhR activation in human hematopoietic progenitor cells (HPs) drives an unprecedented expansion of HPs, megakaryocyte- and erythroid-lineage cells.
See also Concise Review:
The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation.
Platelets help prevent hemorrhage in thrombocytopenic patients and patients with thrombocythemia. A significant problem for multitransfused patients is refractoriness to platelet transfusions. Thus, the ability to generate platelet products ex vivo and platelet products lacking HLA antigens in serum-free media would have clinical value.
An RNA interference-based mechanism used a lentiviral vector to express short-hairpin RNAi targeting β2-microglobulin transcripts in CD34-positive cells. Generated platelets demonstrated an 85% reduction in class I HLA antigens. These platelets appeared to have normal function in vitro
One clinically-applicable strategy for the derivation of functional platelets from human iPSC involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) through doxycycline-dependent overexpression of BMI1 and BCL-XL. The resulting imMKCLs can be expanded in culture over extended periods (4–5 months), even after cryopreservation. Halting the overexpression (by the removal of doxycycline from the medium) of c-MYC, BMI1 and BCL-XL in growing imMKCLs led to the production of CD42b+ platelets with functionality comparable to that of native platelets on the basis of a range of assays in vitro and in vivo.
Thomas et al., describe a forward programming strategy relying on the concurrent exogenous expression of 3 transcription factors: GATA1, FLI1 and TAL1. The forward programmed megakaryocytes proliferate and differentiate in culture for several months with megakaryocyte purity over 90% reaching up to 2x10 mature megakaryocytes per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs.
See also overview
A specialised type of white blood cell, known as cytotoxic T lymphocytes (CTLs), are produced by the immune system and are able to recognise specific markers on the surface of various infectious or tumour cells, causing them to launch an attack to kill the harmful cells. Thence, immunotherapy with functional antigen-specific T cells has potential as a therapeutic strategy for combating many cancers and viral infections. However, cell sources are limited, because they are produced in small numbers naturally and have a short lifespan.
A potentially efficient approach for generating antigen-specific CTLs is to revert mature immune T cells into iPSCs, which possess indefinite proliferative capacity in vitro and after their multiplication to coax them to redifferentiate back into T cells.
Another method combines iPSC and chimeric antigen receptor (CAR)<ref name="doi10.1158/2159-8290.CD-12-0548"></ref> technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture.<ref name="doi10.1038/nbt.2678"></ref> This approach of generating therapeutic human T cells may be useful for cancer immunotherapy and other medical applications.
Invariant natural killer T (iNKT) cells have great clinical potential as adjuvants for cancer immunotherapy. iNKT cells act as innate T lymphocytes and serve as a bridge between the innate and acquired immune systems. They augment anti-tumor responses by producing interferon-gamma (IFN-γ).<ref name="doi10.1155/2012/720803"></ref> The approach of collection, reprogramming/dedifferentiation, re-differentiation and injection has been proposed for related tumor treatment.
Dendritic cells (DC) are specialized to control T-cell responses. DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and after that be completely eliminated. DC-like antigen-presenting cells obtained from human induced pluripotent stem cells can serve as a source for vaccination therapy.
CCAAT/enhancer binding protein-α (C/EBPα) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into iPS cells when co-expressed with transcription factors Oct4, Sox2, Klf4 and Myc. with a 100-fold increase in iPS cell reprogramming efficiency, involving 95% of the population.<ref name="doi10.1038/nature12885"></ref>
Furthermore, C/EBPa can convert selected human B cell lymphoma and leukemia cell lines into macrophage-like cells at high efficiencies, impairing the cells' tumor-forming capacity.<ref name="doi10.1016/j.celrep.2013.03.003"></ref>
The thymus is the first organ to deteriorate as people age. This shrinking is one of the main reasons the immune system becomes less effective with age. Diminished expression of the thymic epithelial cell transcription factor FOXN1 has been implicated as a component of the mechanism regulating age-related involution.
Clare Blackburn and colleagues show that established age-related thymic involution can be reversed by forced upregulation of just one transcription factor – FOXN1 in the thymic epithelial cells in order to promote rejuvenation, proliferation and differentiation of these cells into fully functional thymic epithelium.
This rejuvenation and increased proliferation was accompanied by upregulation of genes that promote cell cycle progression (cyclin D1, ΔNp63, FgfR2IIIb) and that are required in the thymic epithelial cells to promote specific aspects of T cell development (Dll4, Kitl, Ccl25, Cxcl12, Cd40, Cd80, Ctsl, Pax1).
mesenchymal stem/stromal cells (MSCs) are under investigation for applications in cardiac, renal, neural, joint and bone repair, as well as in inflammatory conditions and hemopoietic cotransplantation. This is because of their immunosuppressive properties and ability to differentiate into a wide range of mesenchymal-lineage tissues. MSCs are typically harvested from adult bone marrow or fat, but these require painful invasive procedures and are low-frequency sources, making up only 0.001–0.01% of bone marrow cells and 0.05% in liposuction aspirates. Of concern for autologous use, in particular in the elderly most in need of tissue repair, MSCs decline in quantity and quality with age.
IPSCs could be obtained by the cells rejuvenation of even centenarians. Because iPSCs can be harvested free of ethical constraints and culture can be expanded indefinitely, they are an advantageous source of MSCs. IPSC treatment with SB-431542 leads to rapid and uniform MSC generation from human iPSCs. (SB-431542 is an inhibitor of activin/TGF- pathways by blocking phosphorylation of ALK4, ALK5 and ALK7 receptors.) These iPS-MSCs may lack teratoma-forming ability, display a normal stable karyotype in culture and exhibit growth and differentiation characteristics that closely resemble those of primary MSCs. It has potential for in vitro scale-up, enabling MSC-based therapies. MSC derived from iPSC have the capacity to aid periodontal regeneration and are a promising source of readily accessible stem cells for use in the clinical treatment of periodontitis.
Lai et al., & Lu report the chemical method to generate MSC-like cells (iMSCs), from human primary dermal fibroblasts using six chemical inhibitors (SP600125, SB202190, Go6983, Y-27632, PD0325901, and CHIR99021) with or without 3 growth factors (transforming growth factor-β (TGF-β), basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF)). The chemical cocktail directly converts human fibroblasts to iMSCs with a monolayer culture in 6 days, and the conversion rate was approximately 38%.
Besides cell therapy in vivo, the culture of human mesenchymal stem cells can be used in vitro for mass-production of exosomes, which are ideal vehicles for drug delivery.
Adipose tissue, because of its abundance and relatively less invasive harvest methods, represents a source of mesenchymal stem cells (MSCs). Unfortunately, liposuction aspirates are only 0.05% MSCs. However, a large amount of mature adipocytes, which in general have lost their proliferative abilities and therefore are typically discarded, can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and express multipotent capacities. Compared with adult stem cells, DFAT cells show unique advantages in abundance, isolation and homogeneity. Under proper induction culture in vitro or proper environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. They could also exhibit perivascular characteristics and elicit neovascularization.
Cartilage is the connective tissue responsible for frictionless joint movement. Its degeneration ultimately results in complete loss of joint function in the late stages of osteoarthritis. As an avascular and hypocellular tissue, cartilage has a limited capacity for self-repair. Chondrocytes are the only cell type in cartilage, in which they are surrounded by the extracellular matrix that they secrete and assemble.
One method of producing cartilage is to induce it from iPS cells. Alternatively, it is possible to convert fibroblasts directly into induced chondrogenic cells (iChon) without an intermediate iPS cell stage, by inserting three reprogramming factors (c-MYC, KLF4 and SOX9). Human iChon cells expressed marker genes for chondrocytes (type II collagen) but not fibroblasts.
Implanted into defects created in the articular cartilage of rats, human iChon cells survived to form cartilaginous tissue for at least four weeks, with no tumors. The method makes use of c-MYC, which is thought to have a major role in tumorigenesis and employs a retrovirus to introduce the reprogramming factors, excluding it from unmodified use in human therapy.
The most frequently used sources for reprogramming are blood cells and fibroblasts, obtained by biopsy of the skin, but taking cells from urine is less invasive. The latter method does not require a biopsy or blood sampling. As of 2013, urine-derived stem cells had been differentiated into endothelial, osteogenic, chondrogenic, adipogenic, skeletal myogenic and neurogenic lineages, without forming teratomas. Therefore, their epigenetic memory is suited to reprogramming into iPS cells. However, few cells appear in urine, only low conversion efficiencies had been achieved and the risk of bacterial contamination is relatively high.
Another promising source of cells for reprogramming are mesenchymal stem cells derived from human hair follicles.
The origin of somatic cells used for reprogramming may influence the efficiency of reprogramming, the functional properties of the resulting induced stem cells and the ability to form tumors.
IPSCs retain an epigenetic memory of their tissue of origin, which impacts their differentiation potential.
This epigenetic memory does not necessarily manifest itself at the pluripotency stage – iPSCs derived from different tissues exhibit proper morphology, express pluripotency markers and are able to differentiate into the three embryonic layers in vitro and in vivo. However, this epigenetic memory may manifest during re-differentiation into specific cell types that require the specific loci bearing residual epigenetic marks.
| 36315057 | https://en.wikipedia.org/wiki?curid=36315057 |
Natural_sciences | Arachnoid (botany)
Arachnoid as a descriptive term in botany, refers to organs such as leaves or stems that have a cobwebby exterior appearance, from being covered with fine white hairs, usually tangled. Such material is one common cause of plants having a grey or white appearance. The usages of various authors in distinguishing between "arachnoid" and a few other terms referring to hairiness, such as floccose, pubescent, tomentum, cottony, or villous, tend to be arbitrary, but as a rule the term is best reserved for hairiness lighter than a felted layer, and inclined to rub off or to be easily damaged in other ways. The arachnoid appearance is common on the leaves and stems of various sclerophyllous members of the Asteraceae, such as some thistles.
Nonetheless, "cobwebbiness" is a subjective impression, and in the likes of "Hayworthia arachnoidea" the arachnoid impression arises from the thicket of spinescent leaf denticles that are not at all fine, tangled, or fragile. In the cactus "Cephalocereus senilis", the arachnoid effect arises from long-lasting hairy spines.
| 36318138 | https://en.wikipedia.org/wiki?curid=36318138 |
Natural_sciences | Mena (Mercurian crater)
Mena is a crater in the Beethoven quadrangle on Mercury. It has a diameter of 25 kilometers. Its name was adopted by the International Astronomical Union in 1976. Mena is named for the Spanish poet Juan de Mena, who lived from 1411 to 1456.
| 36322067 | https://en.wikipedia.org/wiki?curid=36322067 |
Natural_sciences | Caño Delgadito orthohantavirus
Caño Delgadito orthohantavirus (CADV) is a hantavirus present in Venezuela. Its natural reservoir is Alston's cotton rat. Transmission among cotton rats appears to be horizontal. While human disease caused by CADV has not yet been identified, it has been isolated from oropharyngeal swabs and urine of infected cotton rats, indicating that it may be infectious to humans in the same manner as other hantaviruses, via inhalation of aerosolized droplets of saliva, respiratory secretions, or urine. CADV was discovered in the 1990s from rodent species in Los Llanos in Venezuela.
| 36326574 | https://en.wikipedia.org/wiki?curid=36326574 |
Natural_sciences | Auguste Eugène Méquignon
Auguste Eugène Méquignon (21 February 1875, in Paris – 1958 in Paris), was a French entomologist. He specialised in Coleoptera, especially Staphyliniformia and Cucujoidea.
He was a member of the Société entomologique de France and was president in 1922.
partial list
| 36327396 | https://en.wikipedia.org/wiki?curid=36327396 |
Natural_sciences | Agence Nationale de Sécurité du Médicament et des Produits de Santé
Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) superseded the tasks and duties of Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS) on 1 May 2012. It is responsible for assessing the benefits and risks associated with the use of health products throughout their life-cycle. ANSM assesses the safety, efficacy and quality of these products and must balance patient safety with access to novel therapies.
The Agence française de sécurité sanitaire des produits de santé (French Agency for the Safety of Health Products), often abbreviated AFSSAPS or AFSSaPS, was a French government institution whose main mission was to assess health risks posed by health products intended for human consumption, particularly pharmaceutical drugs. It was responsible for issuing permits for marketing approval and became the single authority in the regulation of biomedical research.
The agency was latest headed by Dominique Maraninchi and had about 1,000 employees plus 2,000 experts. Its budget amounts to approximately 157 million euros, with the bulk of revenue came from taxes and charges levied on the activity of the pharmaceutical industry.
The Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM), superseded the tasks and duties of the AFSSAPS on 1 May 2012.
| 36332758 | https://en.wikipedia.org/wiki?curid=36332758 |
Natural_sciences | Mike Zuurman
Michael Wilhelmer "Mike" Zuurman (born September 8, 1974 in Veendam) is a Dutch biologist by education and programmer for the non-profit organization Xentax Foundation in Emmen. His professional career is in programming, science and pharmaceuticals. His 'handle' is Mr. Mouse.
| 36337249 | https://en.wikipedia.org/wiki?curid=36337249 |
Natural_sciences | George Meyer-Darcis
Georges Meyer-Darcis, full name Georg Gottlieb August Meyer-Darcis (or Meyer Darcis) (12 September 1860 in Wohlen – 3 January 1913 in Florence) was a Swiss botanist and entomologist.
Georges Meyer-Darcis was the son of a world-famous straw goods manufacturer (Sogin & Meyer). From 1875 to 1878 he was educated in the Technical Department of the cantonal school in Aarau. Encouraged by Professor Mühlberg, he collected rare plants and insects with his friend Samuel Döbeli. After a commercial apprenticeship in Geneva, he managed the straw goods factory. In Geneva, he collected insects in his spare time, encouraged by the curator of the Entomological collections of the University of Geneva Dr. Emil Frey-Gessner (1826–1917).
In addition to his own collections, he purchased world Coleoptera and plant collections, including one by Johann Luzi Krättli (1812–1903), which he then presented to the Botanical Museum of the University of Zurich. Some parts of his beetle collection were sold to the French entomologist René Oberthür and are now preserved in the Muséum national d'Histoire naturelle, Paris.
| 36341988 | https://en.wikipedia.org/wiki?curid=36341988 |
Natural_sciences | Max Bartel
Max Bartel (1879 – 2 July 1914, Nürnberg) was a German entomologist.
Max Bartel was an insect dealer (Insektenhändler) in Berlin. He specialised in Lepidoptera. He edited "Die palaearktischen Grossschmetterlinge und ihre Naturgeschichte". Band 1. Leipzig, (a monograph on butterflies) with Fritz Rühl and wrote pars Sesiidae in Adalbert Seitz Macrolepidoptera of the World - Bartel, M., 1912.– 24. Familie: Ageriidae (Sesiidae) pp. 375–416, pl. 51-52, In A. Seitz (Ed.), 1906-1913."Gross-Schmett.Erde", 2: 479 pp., 56 pls.
| 36342524 | https://en.wikipedia.org/wiki?curid=36342524 |
Natural_sciences | Split networks
For a given set of taxa like X, and a set of splits S on X, usually together with a non-negative weighting, which may represent character changes distance, or may also have a more abstract interpretation, if the set of splits S is compatible, then it can be represented by an unrooted phylogenetic tree and each edge in the tree corresponds to exactly one of the splits. More generally, S can always be represented by a split network, which is an unrooted phylogenetic network with the property that every split s in S is represented by an array of parallel edges in the network.
A split network N can be obtained from a number of different types of data:
| 36356112 | https://en.wikipedia.org/wiki?curid=36356112 |
Natural_sciences | Azagny virus
Azagny virus (AZGV) is an "Orthohantavirus" found in West African pygmy shrews. The virus was named after the Azagny National Park, where some sample collecting occurred.
| 36378177 | https://en.wikipedia.org/wiki?curid=36378177 |
Natural_sciences | RV Southern Surveyor
The RV "Southern Surveyor" was an Australian marine research vessel. It was owned and managed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), with its operations funded by the Australian Government to undertake oceanographic, geoscience, ecosystem and fisheries research. It was built in the UK in 1972 and acquired by CSIRO in 1988. It was replaced in 2014 by the RV "Investigator".
The ship has carried out 111 Marine National Facility research voyages in the course of which she has travelled 481,550 km. Achievements include the discovery of submarine volcanoes between Fiji and Samoa, the compilation of climate records from ancient corals, the production of a carbon chemistry map of the Great Barrier Reef, and the 2006 discovery of a 200 km diameter vortex in the waters above the Perth Canyon off the coast of Rottnest Island, Western Australia.
In 2012 the Southern Surveyor confirmed the 'undiscovery' of Sandy Island.
| 36400868 | https://en.wikipedia.org/wiki?curid=36400868 |
Natural_sciences | Whindust
Whindust is a local name used in Scotland and the North of England referring to fine-grained grit or dust resulting as a by-product from the grinding and breaking of Whinstone.
| 36415769 | https://en.wikipedia.org/wiki?curid=36415769 |
Natural_sciences | Lorenz Oldenberg
Lorenz Oldenberg (2 January 1863, Berlin – 24 May 1931, Berlin) was a German entomologist who specialised in Diptera.
Lorenz Oldenberg was an official at the Patent Office.
partial list
| 36424317 | https://en.wikipedia.org/wiki?curid=36424317 |
Natural_sciences | Johann Egger
Johann Nepomuk Georg Egger (15 May 1804, in Salzburg – 19 March 1866, in Vienna), was an Austrian entomologist who specialised in Diptera.
Egger was a court physician in Vienna.
Egger wrote only one scientific papers Egger, J. 1856. Neue Dipteren-Gattungen und Arten aus der Familie der Tachinarien und Dexiarien nebst einigen andern dipterologischen "Bemerkungen. Verh. Zool-Bot. Ges. Wien" 6: 383-92 but this is an important reference.
His collection is conserved in Naturhistorisches Museum in Vienna.
| 36425203 | https://en.wikipedia.org/wiki?curid=36425203 |
Natural_sciences | RV Investigator
RV "Investigator" is an Australian marine research vessel which was designed by RALion (joint venture between Robert Allan Ltd. and Alion Science and Technology). It was constructed in Singapore and is owned and managed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), through Australia's Marine National Facility, with its operations funded by the Australian Government to undertake oceanographic, geoscience, ecosystem and fisheries research. In May 2009 the Australian Government allocated A$120 million for a new ocean-going research vessel to replace the 1972 built RV "Southern Surveyor", which has served as the principal research ship for Australia's Marine National Facility since 1988. RV "Investigator" was transferred from Sembawang Shipyard to the delivery crew on 5 August 2014 for pre-departure testing and setup. The vessel arrived at its home port of Hobart on 9 September 2014 and was officially launched on 12 December 2014.
The RV "Investigator" is able to accommodate up to 40 scientists, go to sea for up to 60 days at a time and spend up to 300 days of the year at sea on research voyages. Operating costs are estimated to be $140,000 per day. Special features of the ship are a "gondola", similar to a winged keel, mounted 1.2 m below the hull, and two drop keels (which can be lowered to a maximum of 4m below the hull), to carry scientific instruments below the layer of microbubbles created by the movement of the ship’s hull through the water. Such instrumentation includes acoustic mappers, a pelagic sediment profiler to produce maps of the sea floor, and 2 Acoustic Doppler current profilers. The hull and the machinery of the ship have been designed to operate as quietly as possible to enhance its scientific capabilities.
| 36426182 | https://en.wikipedia.org/wiki?curid=36426182 |
Natural_sciences | Abell 222
Abell 222 is a galaxy cluster in the constellation of Cetus. It holds thousands of galaxies together. It is located at a distance of 2.4 billion light-years from Earth.
Astronomers noticed an invisible string of matter was warping spacetime between Abell 222 and Abell 223. Upon further examination by using images from the Japanese Subaru telescope, astronomers discovered that this "invisible matter" is in fact dark matter. The astronomers used gravitational lensing to detect the dark matter filaments. The cluster is connected by a filament of dark matter to Abell 223 that is permeated by hot X-ray emitting gas. Further research shows that this filament only contains about 20 percent of normal matter, the rest is assumed to be dark matter. This is seen to be in good agreement with the cosmological standard model.
5% of the universe is made up of baryonic or ordinary matter which contains protons and neutrons, also known as baryons, and electrons. Baryons and electrons are the foundation for atoms. Astronomers have not been able to locate the full 5% of baryonic matter within other galaxies, stars or gases. After observing gas that connects Abell 222 and Abell 223, scientists believe that the missing baryonic matter is within the gas that bridges the two galaxy clusters. This was difficult to locate due to the fact that the gas had a very low density, which made it hard to detect. This discovery was made possible because of Abell 222’s location. It is within Earth’s line of sight, so scientists were able to see a strong concentration of this gas within a section of the sky.
| 36426438 | https://en.wikipedia.org/wiki?curid=36426438 |
Natural_sciences | Abell 223
Abell 223 is a galaxy cluster. It is located at a distance of 2.4 billion light-years from Earth.
The cluster is connected to nearby cluster Abell 222 by a filament of matter. Research has shown that only 20% of that matter is normal. The rest is thought to be dark matter.
| 36426504 | https://en.wikipedia.org/wiki?curid=36426504 |
Natural_sciences | NGC 2146
NGC 2146 is a barred spiral galaxy type SB(s)ab pec in the constellation Camelopardalis. The galaxy was discovered in 1876 by Friedrich August Theodor Winnecke.
It has a diameter of 80,000 lyr. The galaxy's most conspicuous feature is the dusty lanes of a spiral arm lying across the core of the galaxy as seen from Earth, the arm having been bent 45 degrees by a close encounter with a smaller galaxy possibly NGC 2146a about 0.8 billion years ago. This close encounter is credited with the relatively high rates of star formation that qualify NGC 2146 as a starburst galaxy.
It was host to supernova "SN 2005V", a type Ib/c supernova discovered by LIRIS on 30 January 2005.
"SN 2018zd", a type II supernova (possibly type IIn), was discovered on 2 March 2018 by Koichi Itagaki.
| 36448794 | https://en.wikipedia.org/wiki?curid=36448794 |
Natural_sciences | Inktomi (crater)
Inktomi, also known as The Splat, is a prominent rayed impact crater in diameter located in the southern hemisphere of Saturn's moon Rhea. The crater is named for the Lakota spider-god Iktomi and is located at . Inktomi is thought to be the youngest surface feature on Rhea, with estimates ranging from 8 to 280 million years.
The rayed ejecta pattern indicates an oblique impact occurred from the west. The impact ejected pure water ice from beneath Rhea's surface creating a region contrastingly lighter than the surrounding regions. Recent analysis of "Cassini"s VIMS data revealed clean water ice without impurities at the crater and in its ejecta. Reassessment of the images from orbit, using additional images taken from Inktomi and its surroundings, confirms a continuous ejecta blanket almost devoid of small craters, thus likely a more geologically recent impact. A 3-dimensional anaglyph constructed from "Cassini" VIMS images shows a hilly crater floor with a prominent but topographically low central peak complex. While regular radial secondaries occur outside of the continuous ejecta blanket associated with the bright rays, clusters of numerous small craters could be identified in the eastern part of the crater floor and in the adjacent continuous ejecta. These small craters were most likely created by material ejected from the Inktomi impact at a steep angle.
| 36456363 | https://en.wikipedia.org/wiki?curid=36456363 |
Natural_sciences | Crackle breccia
Crackle breccia is a type of breccia where the clasts have been separated by planes of rupture, but have experienced little or no displacement. The individual clasts in crackle breccia must not have experienced more than 10° average rotation.
| 36458036 | https://en.wikipedia.org/wiki?curid=36458036 |
Natural_sciences | Karim Yassen
Karim Yassen is a Kurdish professor, who is known for finding the enzyme which causes gum disease. The research was done at Jagiellonian University in Poland.
He works in the department of biology of Irbil's Salahaddin University-Erbil as a lecturer.
| 36463855 | https://en.wikipedia.org/wiki?curid=36463855 |
Natural_sciences | C20H32N2O
The molecular formula CHNO may refer to:
| 36477688 | https://en.wikipedia.org/wiki?curid=36477688 |
Natural_sciences | LARMOR neutron microscope
The LARMOR neutron microscope is a microscope based on the principle of neutron scattering. It is named in honor of Joseph Larmor and the principle of larmor precession that will increase resolution and accuracy. It is located at ISIS Neutron and Muon Source in Oxfordshire.
LARMOR will be used to make high-precision, deep images of physical objects. Since neutrons bear no electrical charge, neutron beams can penetrate deeply into materials. By examining the few interactions that neutrons do have with atoms they encounter and enhancing the imaging using larmor precession, the microscope is predicted to create images with an atom-level resolution. The microscope will allow for observation of magnetic materials, complex liquids and living specimens. An example of application of this research is improved electronics and charge storage in lithium-ion batteries.
LARMOR is a joint project of the Delft University of Technology, the Eindhoven University of Technology, the University of Groningen and the Science and Technology Facilities Council's ISIS Neutron and Muon Source . It is funded jointly by the participating Dutch universities and ISIS Neutron and Muon Source, and the Dutch NWO will contribute 2.3 million Euros. One-third of the microscope's time will be reserved for research from the Netherlands.
| 36493464 | https://en.wikipedia.org/wiki?curid=36493464 |
Natural_sciences | Franz Josef Kupido
Franz Josef Kupido sometimes Cupido (6 August 1786, Brno- 17 December 1869) was a Czech entomologist principally interested in Lepidoptera.
Franz Josef Kupido was a "Beamter". His collection is in the Moravian Museum, Brno. In 1825 Kupido described the autumn emperor moth, "Perisomena caecigena".
| 36499196 | https://en.wikipedia.org/wiki?curid=36499196 |
Natural_sciences | Reaktor Serba Guna G.A. Siwabessy
Reaktor Serba Guna–Gerrit Augustinus Siwabessy (RSG-GAS) "(Multipurpose Reactor–Gerrit Augustinus Siwabessy)" is a research reactor located in the Serpong neighborhood of South Tangerang, Banten, Indonesia. The reactor plays an important role in the Centre for Nuclear Industry Development, at Puspiptek, Serpong to serve other supporting laboratories, namely, radioisotope production, nuclear material science, reactor fuel element development, reactor safety, waste treatment, radio-metallurgy and nuclear-mechano laboratories.
The reactor was constructed through a $50 million contract with Interatom Internationale Atomreaktorbau GmbH, a unit of the West German steelmaker Kraftwerke Union, which was awarded in 1981. The reactor's fuel rods have originated in the United States, France and the United Kingdom; the fuel was enriched in the United States and Russia. The International Atomic Energy Agency safeguards the reactor. It was inaugurated by the second President of Indonesia, Suharto on August 20, 1987. The reactor was named after G.A. Siwabessy, Minister of Health and Minister of Atomic Energy under both president Sukarno and Suharto.
RSG-GAS went to its first criticality on July 29, 1987. The nominal power of 30 MW thermal was achieved on March 23, 1992 at the sixth core containing 40 standard fuel elements and 8 control fuel elements.
| 36508850 | https://en.wikipedia.org/wiki?curid=36508850 |
Natural_sciences | Heinrich Ribbe
Heinrich Ribbe (1832-1898) was a German entomologist.
Heinrich Ribbe was an insect dealer in Dresden and Berlin. In 1876 he collected trade insects in the Crimea and in 1878 he collected for Otto Staudinger and Andreas Bang-Haas in Panama and Chiriqui. His private collection is in the State Museum of Zoology, Dresden.
| 36519826 | https://en.wikipedia.org/wiki?curid=36519826 |
Natural_sciences | August Friedrich Böttcher
August Friedrich Böttcher (5 October 1825 – 20 November 1900) was a German entomologist.
He was born in Berlin, where he became an insect dealer.
| 36520038 | https://en.wikipedia.org/wiki?curid=36520038 |
Natural_sciences | Robert Brendel
Robert Brendel (c. 1821–1898) and his son Reinhold Brendel (c. 1861–1927) were botanical modelmakers in first Breslau then Grunewald Berlin.
They produced accurate, large-scale models of plant structures. These were sold to technical universities teaching practical botany.
| 36520327 | https://en.wikipedia.org/wiki?curid=36520327 |
Natural_sciences | NGC 4700
NGC 4700 is a spiral galaxy located about 50 million light years away in the constellation of Virgo. NGC 4700 was discovered in March 1786 by the British astronomer William Herschel who noted it as a "very faint nebula".
NGC 4700 was imaged by Hubble in 2012, showing an abundance of star-forming regions similar to the Orion Nebula.
| 36522126 | https://en.wikipedia.org/wiki?curid=36522126 |
Natural_sciences | Achávalite
Achávalite is a selenide mineral that is a member of the nickeline group. It has only been found in a single Argentinian mine system, being first discovered in 1939 in a selenide deposit. The type locality is Cacheuta mine, Sierra de Cacheuta, Mendoza, Argentina.
| 36538030 | https://en.wikipedia.org/wiki?curid=36538030 |
Natural_sciences | Cattle creep
A cattle creep is a small, field-to-field access for farm animals, usually to allow passage beneath an obstacle such as a road, canal, or railway embankment.
As they are intended primarily for cattle or other livestock, cattle creeps usually have a low head height and are uncomfortable for humans to use.
On Dartmoor, in south west England, the term sheep creep is used to describe a purposely constructed gap in the base of a drystone wall, commonly topped with a granite lintel. The gap allows sheep to pass from field to field, but is deliberately too small for cattle or ponies.
| 36540089 | https://en.wikipedia.org/wiki?curid=36540089 |
Natural_sciences | Palomar Distant Solar System Survey
The Palomar Distant Solar System Survey (PDSSS) was a wide-field survey aimed at finding distant trans-Neptunian objects that used the robotic 1.2 m Samuel Oschin Telescope at Palomar Observatory and the QUEST large-area CCD camera.
The survey was specifically designed to identify putative members of a Sedna-like population with perihelia greater than 45 AU. The limiting magnitude of this study was 21.3 in the R-band, it was sensitive out to distances of 1000 AU, and 12,000 square degrees of sky were searched. This observing program was responsible for the discovery of 25 minor planets including trans-Neptunian objects and centaurs. and Gǃkúnǁʼhòmdímà () were among the objects discovered by this survey. It redetected Sedna but no other objects in Sedna-like orbits were identified.
| 36548291 | https://en.wikipedia.org/wiki?curid=36548291 |
Natural_sciences | Helmholtz flow
Helmholtz flow is a term used in fluid mechanics for flow with free streamlines or vortex sheets.
| 36549035 | https://en.wikipedia.org/wiki?curid=36549035 |
Natural_sciences | August Alphonse Derbès
August Alphonse Derbès (8 May 1818, Marseille – 27 January 1894, Marseille) was a French professor of naturalist, zoologist and botanist at the University of Marseille who studied reproduction of sea urchins and of algae. Derbès was the first scientist to observe the fertilization of an egg in an animal when he detailed the process of an envelope forming around the gamete during sea urchin reproduction, a process now known to be associated with Ca release.
| 36571110 | https://en.wikipedia.org/wiki?curid=36571110 |
Natural_sciences | Pierre-Aimé Millet
Pierre-Aimé Millet de la Turtaudière (1783 in Angers – 1873) was a French naturalist.
He was Secrétaire Général de la Société d'Agriculture d' Angers.
Partial list
See also WorldCat listings online here
| 36574871 | https://en.wikipedia.org/wiki?curid=36574871 |
Natural_sciences | Vasiliy Lindholm
Vasiliy Adolfovich Lindholm (; 1874 – 17 September 1935), also published as Wilhelm Adolf Lindholm, was a Russian malacologist and herpetologist.
Lindholm was a curator at the Zoological Museum of the Zoological Institute of the Russian Academy of Sciences in Leningrad. He published works on the molluscs of Lake Baikal, the Crimea, the Caucasus and other parts of the U.S.S.R., and on Palaearctic molluscs generally. He also studied amphibians and reptiles, and described three new species of reptiles. A frog "Afrixalus lindholmi" is named for him, sometimes known as Lindholm's banana frog.
| 36584185 | https://en.wikipedia.org/wiki?curid=36584185 |
Natural_sciences | Kálmán Lambrecht
Kálmán Lambrecht (1889–1936) was a Hungarian palaeontologist, best known for his work on fossil birds. He authored the “Handbuch der Palaeornithologie”, an exhaustive review of fossil birds published in 1933. Positions held include librarianship of the Geological Survey of Hungary. He died of heart failure in Budapest.
| 36590966 | https://en.wikipedia.org/wiki?curid=36590966 |
Natural_sciences | Society for the Preservation of Natural History Collections
The Society for the Preservation of Natural History Collections (abbreviated SPNHC, often pronounced "spinach") "is an international society whose mission is to improve the preservation, conservation and management of natural history collections to ensure their continuing value to society".
Founded in 1985, the society was created to cater to the needs of those involved in the care, management and development of natural history collections. Society activities include annual meetings, the publication of a newsletter, and an active list-serv in which members consult one another about natural history collections management issues. The mission of SPNHC continues to grow, broadly encompassing archival materials such as field notes, and new and growing efforts in digitization and mobilization of collections resources.
| 36591692 | https://en.wikipedia.org/wiki?curid=36591692 |
Natural_sciences | NGC 1187
NGC 1187 is a spiral galaxy located about 60 million light-years away in the constellation of Eridanus. NGC 1187 has hosted two supernova explosions since the 1980s. In October 1982, the first supernova seen in NGC 1187 — SN 1982R was discovered at La Silla Observatory and, in 2007, the amateur astronomer Berto Monard in South Africa spotted another supernova in this galaxy — SN 2007Y.
| 36605602 | https://en.wikipedia.org/wiki?curid=36605602 |
Natural_sciences | Earle Hesse Kennard
Earle Hesse Kennard (August 2, 1885 – January 31, 1968) was a theoretical physicist and professor at Cornell University.
Kennard was born in Columbus, Ohio and studied at Pomona College and Oxford University as part of a Rhodes Scholarship. He went on to earn his Ph.D. from Cornell in 1913, where he would continue most of his scientific career. During a 1926 sabbatical spent at the University of Göttingen, he learned the newly developing quantum mechanics of Werner Heisenberg and Pascual Jordan. With this knowledge, he derived the first rigorous form of the uncertainty principle and fully solved several simple quantum mechanics problems for the first time. In 1926, he was appointed professor of physics at Cornell, which he remained until 1946.
In 1941, still at Cornell, he became a part-time consultant at the David Taylor Model Basin (DTMB), the United States Navy modelling facility. In the period 1946–49 he was the head of the hydromechanics laboratory, and from 1950 until 1957 he was head of the structural mechanics laboratory. From 1957 until his retirement in 1960 he was a general scientific consultant to the commanding officer of the DTMB. Also after his retirement he continued to work for the DTMB under contract. Much of his research for the Navy focussed on hydrodynamics and elasticity, in particular on the theory of potential flow, the physics of underwater explosions and structural vibrations.
| 36613133 | https://en.wikipedia.org/wiki?curid=36613133 |
Natural_sciences | Sagittarius Stream
In astronomy, the Sagittarius Stream is a long, complex, structure made of stars that wrap around the Milky Way galaxy in an almost polar orbit. It consists of tidally stripped stars from the Sagittarius Dwarf Elliptical Galaxy resulting from the process of merging with the Milky Way over a period of billions of years.
This stellar stream was originally proposed in 1995 by Donald Lynden-Bell after analyzing the distribution of globular clusters in the Milky Way. The actual structure was identified by Newberg et al. (2002) and Majewski et al. (2003) using data from the 2MASS and SDSS surveys. In 2006, Belokurov and his collaborators found that the Sagittarius Stream has two branches.
The shredding apart of a large intruding collection of stars in the indefinite past appears to have sent oscillations analogous to sound waves through the Milky Way spiral arm structure. The effects of the oscillations are observed today as vertically stacked layers of alternately denser and sparser star distributions above and below the Solar System. Presently, the Sagittarius Stream is positioned relative to the observed layers such that its progenitor, the Sagittarius Dwarf Elliptical Galaxy, is the strongest candidate intruder whose wake left behind the disturbance in the spiral arms.
| 36613701 | https://en.wikipedia.org/wiki?curid=36613701 |
Natural_sciences | Tony Swain (chemist)
Tony Swain (1922–1987) was a chemist known for his definition of a plant polyphenol with Bate-Smith, Haslam and White, which includes specific structural characteristics common to all phenolics having a tanning property. It is referred to as the White–Bate-Smith–Swain–Haslam (WBSSH) definition.
The discovery in 1943 by Martin and Synge of paper chromatography provided for the first time the means of surveying the phenolic constituents of plants and for their separation and identification. There was an explosion of activity in this field after 1945, none more so than that of Bate-Smith and Tony Swain. He worked with Edgar C. Bate-Smith at Cambridge University.
Tony Swain was one of the first editors of "Phytochemistry" with Jeffrey Harborne. He started the sister journal "Biochemical Systematics" in 1973, renamed "Biochemical Systematics and Ecology" in the next year.
| 36665511 | https://en.wikipedia.org/wiki?curid=36665511 |
Natural_sciences | Flick (physics)
In optical engineering and telecommunications engineering, the flick is a unit of spectral radiance. One flick corresponds to a spectral radiance of 1 watt per steradian per square centimeter of surface per micrometer of span in wavelength (W·sr·cm·μm). This is equivalent to 10 watts per steradian per cubic meter (W·sr·m). In practice, spectral radiance is typically measured in microflicks (10 flicks). One microflick is equivalent to 10 kilowatts per steradian per cubic meter (kW·sr·m).
In radio astronomy, the unit flik was coined by a group at Lockheed in Palo Alto, California as a substitute for the SI derived unit W cm sr µm, or watts divided by centimeters squared, steradians, and micrometers. While it started out used only in Lockheed, many in the radio astronomy field adopted its use.
| 36687166 | https://en.wikipedia.org/wiki?curid=36687166 |
Natural_sciences | Moisture expansion
Moisture expansion is the tendency of matter to change in volume in response to a change in moisture content. The macroscopic effect is similar to that of thermal expansion but the microscopic causes are very different. Moisture expansion is caused by hygroscopy.
| 36688650 | https://en.wikipedia.org/wiki?curid=36688650 |
Natural_sciences | NGC 2119
NGC 2119 (also identified as UGC 3380 or PGC 18136) is an elliptical galaxy in the constellation Orion. It was discovered by Édouard Stephan on January 9, 1880.
| 36694720 | https://en.wikipedia.org/wiki?curid=36694720 |
Natural_sciences | Lagrangian particle tracking
In experimental fluid mechanics, Lagrangian Particle Tracking refers to the process of determining long 3-Dimensional trajectories of small neutrally buoyant particles (flow tracers) that are freely suspended within a turbulent flow field. These are usually obtained by 3-D Particle Tracking Velocimetry. A collection of such particle trajectories can be used for analyzing the Lagrangian dynamics of the fluid motion, for performing Lagrangian statistics of various flow quantities etc.
In computational fluid dynamics, the Lagrangian particle tracking (or in short LPT method) is a numerical technique for simulated tracking of particle paths Lagrangian within an Eulerian phase. It is also commonly referred to as Discrete Particle Simulation (DPS). Some simulation cases for which this method is applicable are: sprays, small bubbles, dust particles, and is especially optimal for dilute multiphase flows with large Stokes number.
| 36714938 | https://en.wikipedia.org/wiki?curid=36714938 |
Natural_sciences | Longest linear sequence
In synthetic chemistry, the longest linear sequence, commonly abbreviated as LLS, is the largest number of reactions required to go from the starting materials to the products in a multistep sequence.
This concept is very important when trying to optimize a synthetic plan. Since every reaction step can decrease the yield of the product, reducing the value of the LLS is a good way to increase the quantity of chemicals formed at the end: this can be done by devising quicker methods to couple the fragments or by introducing convergence. However, improving sequences which are not the longest linear one will generally not produce an overall enhancement to the yield of the reaction since the benefits incur in intermediates that were already present in excess, assuming that the yields for each of the steps are roughly equal.
| 36715119 | https://en.wikipedia.org/wiki?curid=36715119 |
Natural_sciences | NGC 5970
NGC 5970 is a large barred-spiral galaxy located about 90 million light years away in the constellation Serpens Caput. It appears to have two satellite or companion galaxies.
NGC 5970 can be seen 1° southwest of the star Chi Serpentis. A faint halo of dust can be seen around the galaxy's outer spiral arms.
| 36741953 | https://en.wikipedia.org/wiki?curid=36741953 |
Natural_sciences | Bennett's laws
Bennett's laws of quantum information are:
where formula_1 indicates "can do the job of".
These principles were formulated around 1993 by Charles H. Bennett.
| 36750998 | https://en.wikipedia.org/wiki?curid=36750998 |
Natural_sciences | Llewellyn separator
The Llewellyn separator is a membrane molecular separator, a device for interfacing the effluence from a gas chromatograph to the ion source input of a mass spectrometer by changing a rather large (e.g. 10^4 TorrLitre) dilute (e.g. 1 part of vapour in 10^5 parts of carrier gas) gas flow into a small(e.g. <10^-3 TorrLitre) concentrated flow that can be admitted to the vacuum of the mass spectrometer. It is typically based on the substance passing through a few silicone rubber membranes in series. In order for the molecules of interest to be enriched in relation to the small and light carrier gas molecules the former must be captured by (dissolved in) the membrane polymer. The selection properties may be augmented by a liquid stationary phase on the membrane.
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| 36754975 | https://en.wikipedia.org/wiki?curid=36754975 |
Natural_sciences | Hypogene
In ore deposit geology, hypogene processes occur deep below the earth's surface, and tend to form deposits of primary minerals, as opposed to supergene processes that occur at or near the surface, and tend to form secondary minerals.
At great depth the pressure is high, and water can remain liquid at temperatures well above 100 °C. Hot aqueous solutions originating in the magma contain metal and other ions derived from the magma itself, and also from leaching of surrounding rocks. Hypogene deposition processes include crystallization from the hot aqueous solutions rising through the earth's crust, driven by heat provided by the magma.
Major dissolved components are chlorine, sodium, calcium, magnesium and potassium, and other important components include iron, manganese, copper, zinc, lead, sulfur (as SO or S or both) carbon (as HCO and CO) and nitrogen (as NH). Most ore fluids contain chloride as the dominant anion.
As the solutions rise the temperature and pressure fall. Eventually a point is reached where the minerals start to crystallise out. Minerals formed in this way are called primary, or hypogene, minerals. Sulfur is a common component of the fluids, and most of the common ore metals, lead, zinc, copper, silver, molybdenum and mercury, occur chiefly as sulfide and sulfosalt minerals.
Examples of primary minerals formed in this way include the sulfide minerals pyrite (FeS), galena (PbS), sphalerite (ZnS), and chalcopyrite (CuFeS).
The word hypogene is derived from the Greek "hypo-" meaning "under" and "-gene" meaning "born" or "produced". The terms "hypogene" and "supergene" refer to the depth at which they occur.
| 36757278 | https://en.wikipedia.org/wiki?curid=36757278 |
Natural_sciences | British Bryological Society
The British Bryological Society is an academic society dedicated to bryology, which encourages the study of bryophytes – mosses and liverworts. It publishes the peer-reviewed "Journal of Bryology".
| 36758008 | https://en.wikipedia.org/wiki?curid=36758008 |
Natural_sciences | Boron aluminum titanium hydride
Boron Aluminum Titanium Hydride (BATH) was developed as a radiation shielding material in the NERVA project for space nuclear thermal propulsion applications.
| 36763436 | https://en.wikipedia.org/wiki?curid=36763436 |
Natural_sciences | Tengion
Tengion, Inc. is an American development-stage regenerative medicine company founded in 2003 with financing from J&J Development Corporation, HealthCap and Oak Investment Partners, which is headquartered in Winston-Salem, North Carolina. Its goals are discovering, developing, manufacturing and commercializing a range of replacement organs and tissues, or neo-organs and neo-tissues, to address unmet medical needs in urologic, renal, gastrointestinal, and vascular diseases and disorders. The company creates these human neo-organs from a patients own cells or autologous cells, in conjunction with its Organ Regeneration Platform. The company declared Chapter 7 bankruptcy in December 2014, and it, along with its assets and tissue engineering samples, have been bought back by its creditors and former executives as of March 2015. The purchase was expedited, so that time-sensitive research can continue.
Founded in 2003 and formerly headquartered in East Norriton, Pennsylvania before moving to Winston-Salem, North Carolina in 2012, Tengion went public in 2010, after its stock has been approved for listing on the NASDAQ, through a $26 million IPO to help advance its research and development activities. Some of the groundbreaking regenerative medicine technologies of Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, were the core from where those research and development activities developed. On September 4, 2012, Tengion received a notice from NASDAQ stating that the company had not regained compliance with NASDAQ Listing Rule 5550(b)(1) and that its common stock would cease trading on the NASDAQ Capital Market effective on September 6, 2012, and would begin trading on the OTCQB tier of the OTC Marketplace. The company was bought by former executives and creditors after declaring bankruptcy in 2014.
All current Tengion's regenerative medicine product candidates are investigational and will not be commercially available until the completion of clinical trials and the review and approval of associated marketing applications by the Food and Drug Administration.
Its most advanced candidate is the Neo-Urinary Conduit. A Phase I clinical trial of the Tengion Neo-Urinary Conduit was completed in several health care institutions, in patients with bladder cancer who require a total cystectomy. The trial ended in December 2014, however information on the results has not yet been made publicly available.
The company also develops the Neo-Bladder Augment, a Phase II clinical trial product for the treatment of neurogenic bladder resulting from spina bifida in pediatric patients, as well as neurogenic bladder resulting from spinal cord injury in adult patients; the Neo-Bladder Replacement to serve as a functioning bladder, eliminating the need for an ostomy bag, for patients who have their bladders removed due to cancer; and the Neo-Kidney Augment to prevent or delay dialysis by increasing renal function in patients with advanced chronic kidney disease.
In addition, it is involved in developing the Neo-GI Augment, a gastrointestinal development program; and Neo-Vessel Replacement, which targets various blood vessel applications consisting of vascular access grafts, arterio-venous, and shunts for patients with ESRD (end stage renal disease) undergoing hemodialysis treatment, as well as for vessel replacement for patients undergoing coronary or peripheral artery bypass procedures.
| 36772719 | https://en.wikipedia.org/wiki?curid=36772719 |
Natural_sciences | Mitja Brodar
Mitja (Demetrij) Brodar (1921 – 16 February 2012) was a Slovenian paleontologist. He was a son of Srečko Brodar, a pioneer of the study of the Paleolithic period in Slovenia. In the sixties and seventies of the 20th century Brodar, together with France Osole, was leading the Paleolithic research in Slovenia.
He was born in 1921 in Celje where his father was at the time teaching science at the Grammar school in Celje.
During Italian occupation of Ljubljana in WW2 he joined the anti-Nazi resistance movement, was captured in 1942 and sent to the Italian concentration camps in Rab, Reka [Fiume] and in Visco.
Brodar studied civil engineering at the University of Ljubljana, at the wish of his father (graduated in 1949). Later he also studied geology and paleontology with graduation in 1953. Since 1952 he was a member of Ljubljana Cave Exploration Society (DZRJL). Between 1954 and 1956 and in 1960 he was excavating the cave Mokriška jama. He received PhD in 1959 with a thesis on those excavations. Betal Rock Shelter () is another site he was excavating.
He helped establish and was during the 1970s president of the Slovene archaeological association. Together with his father he wrote a book on Potok Cave () excavations.
According to Brodar, the Divje Babe flute is a product of Cro-Magnon, modern human, and not Neanderthal.
| 36774535 | https://en.wikipedia.org/wiki?curid=36774535 |
Natural_sciences | Philipp Maximilian Opiz
Philipp (Filip) Maximilian Opiz (5 June 1787 in Čáslav – 20 May 1858 in Prague) was a Czech-German forester and botanist.
Beginning in 1805 he served as a cameral-beamter in his hometown of Čáslav, later working in Pardubice (from 1808) and Prague (from 1814). In 1831 he became a "Forstamtsconcipist" (forestry official).
He was the taxonomic authority of numerous plant species, and the creator of many sets of exsiccatae. In 1830 Carl Borivoj Presl named the genus "Opizia" in his honor.
| 36774855 | https://en.wikipedia.org/wiki?curid=36774855 |
Natural_sciences | Autochthon (geology)
An autochthon in structural geology is a large block or mass of rock which is in the place of its original formation relative to its basement or foundation rock. It can be described as rooted to its basement rock as opposed to an allochthonous block or nappe which has been relocated from its site of formation.
While an autochthon may have experienced some minor shifting, an allochthonous block will have moved at least a few kilometres. If an overlying allochthon has an opening or hole which exposes the underlying autochthonous material, the hole is called a window (or Fenster).
Authochthous sediment is sediment found at or very close to its site of deposition.
The etymology of the term is from Greek: 'autos' means self, and 'chthon' means earth.
| 36795154 | https://en.wikipedia.org/wiki?curid=36795154 |
Natural_sciences | Stanisław Baranowski
Stanisław Baranowski (25 March 1935 – 27 August 1978) was a Polish glaciologist and leader or member of a number of scientific expeditions to Spitsbergen and Antarctica. He died as a result of an accident near the Henryk Arctowski Polish Antarctic Station while on expedition. At the time of his death, he was head of the Department of Metereology and Climatology at the University of Wrocław.
Stanisław Baranowski Spitsbergen Polar Station and Baranowski Glacier are named after him.
Stanisław Baranowski was born in Gdynia, Poland on 25 March 1935 and graduated from the University of Wrocław in 1955. He carried out studies in glaciology and climatology and participated in many polar expeditions, beginning with the expedition to Spitsbergen during the International Geophysical Year (1957–1958). Subsequently, he organized and led a number of Polish expeditions to that region, as well as to Canada, Iceland and the Sudety Mountains in Poland. He wrote over fifty scientific articles and papers. In 1971, he became a docent and the head of the Department of Metereology and Climatology at the University of Wrocław. He received his habilitation in 1976.
In January 1978, while sleeping near the Henryk Arctowski Polish Antarctic Station on King George Island in the South Shetland Islands, he was poisoned by gas escaping from a leaking cylinder. Despite receiving medical treatment, he never regained consciousness and died in a hospital in Bytom, Poland on 27 August 1978.
His obituary, published in the "Journal of Glaciology", stated the following: "Stanisław Baranowski was widely known and universally liked, and it is especially tragic that he died so young and while at the height of his creative powers."
The polar station he had founded in Spitsbergen was named the Stanisław Baranowski Spitsbergen Polar Station in his memory. A commemorative plaque has been put up at the Henryk Arctowski Polish Antarctic Station where he suffered his accident. The Baranowski Glacier is also named after him.
| 36795236 | https://en.wikipedia.org/wiki?curid=36795236 |
Natural_sciences | Lars Skattebøl
Lars Skattebøl FRSC (born 16 July 1927 in Bærum) is a Norwegian scientist and professor emeritus at the University of Oslo. The Skattebøl rearrangement, a chemical reaction, was named after his discovery.
Skattebøl received his degree in engineering from Norwegian Institute of Technology in 1951 and a doctorate in chemistry from the University of Manchester in 1956. He has worked as a researcher for Union Carbide in Brussels, at SINTEF in Trondheim as well as Norsk Hydro.
As a scholar, Skattebøl has been employed as professor in chemistry at the Oslo University and the University of Tromsø. He has received a number of awards and is a fellow of several scientific academies in his native country, including the Norwegian Academy of Science and Letters, the Royal Norwegian Society of Sciences and Letters, The Royal Society of Chemistry and the American Chemical Society. He chaired the Norwegian Chemical Society for six years, is now an honorary member there, and was an editorial board member of "Acta Chemica Scandinavica".
| 36799714 | https://en.wikipedia.org/wiki?curid=36799714 |
Natural_sciences | Alberto Cambrosio
Alberto Cambrosio is a sociologist of biomedicine at McGill University. He earned his PhD in History and Sociology of Science from the Université de Montréal. He holds a bachelor's degree in Biology from the University of Basel, Switzerland, and a master's degree in Environmental Science from the Université de Sherbrooke, Canada.
He is widely published, and has written three books. In 2005, he received the Ludwik Fleck Prize from the Society for Social Studies of Science for his book "Biomedical Platforms" with historian Peter Keating.
He is Professor and former Chair of the Department of Social Studies of Medicine at McGill University. Since 2011 he has been a guest professor at the Center for the Sociology of Organizations in Paris, France.
| 36799789 | https://en.wikipedia.org/wiki?curid=36799789 |
Natural_sciences | Bringelly Shale
Bringelly Shale is a component of the Wianamatta group of sedimentary rocks in the Sydney Basin of eastern Australia. It was formed in the Triassic Period. It is most often seen in the western parts of the city. The shale has its greatest geographical extent at Bringelly, near the suburb of Liverpool. It is similar to Ashfield Shale, though differing in having a greater amount of sandstone and lacking sideritic mudstone bands. The average thickness is around 60 metres. The Bringelly Shale was deposited in a swampy alluvial plain with meandering streams flowing from the west forming discontinuous beds of sandstone.
Sydney Basin, Hawkesbury sandstone, Ashfield Shale, Wianamatta shale, Mittagong formation and Narrabeen Group.
| 36804196 | https://en.wikipedia.org/wiki?curid=36804196 |
Natural_sciences | Vaupés Arch
The Vaupés Arch is a hydrographic feature in the geology of Colombia. The Vaupés Arch forms the major drainage divide in the southern extent of the "llanos" region of eastern Colombia and the western slopes of the Guiana Shield in Venezuela. The Vaupés Arch is the result of an episode of tectonic uplift that occurred approximately 8 to 10 Ma. The rise of the Vaupés Arch divided the basin of the Amazon from the headwaters of the Orinoco for the first time. Much of the Arch is now buried under thick sediments washed from the Andes. Shifting meanders of the area's numerous waterways have spread these sediments evenly over the flat alluvial plain, which has very little relief. In modern times the Casiquiare canal, to the south of the Arch, reconnects the two headwater basins, the Upper Orinoco and the Upper Rio Negro, a major Amazon tributary.
| 36817758 | https://en.wikipedia.org/wiki?curid=36817758 |
Natural_sciences | Franklin Sibly
Thomas Franklin Sibly K.B.E. (25 October 1883 – 13 April 1948) was a British geologist who had a distinguished career in University administration, being first Principal of University College, Swansea (1920), and later Vice-Chancellor of the University of Wales, Principal of the University of London and from 1929 to 1946 Vice-Chancellor of the University of Reading.
| 36827569 | https://en.wikipedia.org/wiki?curid=36827569 |
Natural_sciences | Moaning sandbar
Moaning sandbars are harbor shoals that are known for tidal noises. Water flowing over a sandbar, typically around low tide, can coincide with both low, sustained noises and turbulence dangerous for smaller boats. In English-speaking culture, phrases such as "moaning of the bar" connect these sounds with mortal danger.
In the mid-19th-century, the phrase "the harbor bar be moaning" in the poem and lyric "Three Fishers" connected working-class suffering to the noises.
Later in that century, Alfred Lord Tennyson wrote "Crossing the Bar", coupling "May there be no moaning of the bar" with images of life's end, and then designated it as essentially his own requiem. This came soon after his making a trying sea journey. It is speculated that on the same trip, he may have heard such sounds at Salcombe, which has had a long history of wrecks. That idea is enhanced by the capsizing, three decades later, of Salcombe's town lifeboat "The William and Emma" on the Salcombe bar, with a fatality rate of 87%.
| 36828359 | https://en.wikipedia.org/wiki?curid=36828359 |
Natural_sciences | Jean-Christophe Balouet
Jean-Christophe Balouet (born 12 November 1956) is a French palaeontologist. He has collaborated extensively with Storrs Olson of the Smithsonian Institution on palaeornithological research on the extinct birds of New Caledonia in the south-west Pacific region.
| 36829250 | https://en.wikipedia.org/wiki?curid=36829250 |
Natural_sciences | 3D cell culturing by magnetic levitation
3D cell culture by the magnetic levitation method (MLM) is the application of growing 3D tissue by inducing cells treated with magnetic nanoparticle assemblies in spatially varying magnetic fields using neodymium magnetic drivers and promoting cell to cell interactions by levitating the cells up to the air/liquid interface of a standard petri dish. The magnetic nanoparticle assemblies consist of magnetic iron oxide nanoparticles, gold nanoparticles, and the polymer polylysine. 3D cell culturing is scalable, with the capability for culturing 500 cells to millions of cells or from single dish to high-throughput low volume systems. Once magnetized cultures are generated, they can also be used as the building block material, or the "ink", for the magnetic 3D bioprinting process.
Standard monolayer cell culturing on tissue culture plastic has notably improved our understanding of basic cell biology, but it does not replicate the complex 3D architecture of in vivo tissue, and it can significantly modify cell properties. This often compromises experiments in basic life science, leads to misleading drug-screening results on efficacy and toxicity, and produces cells that may lack the characteristics needed for developing tissue regeneration therapies.
The future of cell culturing for fundamental studies and biomedical applications lies in the creation of multicellular structure and organization in three-dimensions. Many schemes for 3D culturing are being developed or marketed, such as bio-reactors or protein-based gel environments.
A 3D cell culturing system known as the Bio-Assembler™ uses biocompatible polymer-based reagents to deliver magnetic nanoparticles to individual cells so that an applied magnetic driver can levitate cells off the bottom of the cell culture dish and rapidly bring cells together near the air-liquid interface. This initiates cell-cell interactions in the absence of any artificial surface or matrix. Magnetic fields are designed to rapidly form 3D multicellular structures in as little as a few hours, including expression of extracellular matrix proteins. The morphology, protein expression, and response to exogenous agents of resulting tissue show great similarity to in vivo results.
3D cell culturing by magnetic levitation method (MLM) was developed from collaboration between scientists at Rice University and University of Texas MD Anderson Cancer Center in 2008. Since then, this technology has been licensed and commercialized by Nano3D Biosciences.
Above is a picture showing 3D cell culturing through magnetic levitation with the Bio-Assembler cell culturing system. (A) A magnetic iron oxide nanoparticle assembly known as Nanoshuttle is added and dispersed over cells and the mixture is incubated. (B) After incubation with Nanoshuttle, cells are detached and transferred to a petri dish. (C) A magnetic drive is then placed on top of a petri dish top. (D) The magnetic field causes cells to rise to the air–medium interface. (E) Human umbilical vein endothelial cells (HUVEC) levitated for 60 minutes (left images) and 4 hours (right images) (Scale bar, 50 μm). The onset of cell-cell interaction takes place as soon as cells levitate, and 3D structures start to form. At 1 hour, the cells are still relatively dispersed, but they are already showing some signs of stretching. Formation of 3D structures is visible after 4 hours of levitation (arrows).
Protein expression in levitated cultures shows striking similarity to in vivo patterns. N-cadherin expression in levitated human glioblastoma cells was identical to the expression seen in human tumor xenografts grown in immunodeficient mice, while standard 2D culture showed much weaker expression that did not match xenograft distribution as shown in the picture below. The transmembrane protein N-cadherin is often used as an indicator of in-vivo-like tissue assembly in 3D culturing.
In the picture above, distribution of N-cadherin (red) and nuclei (blue) in human brain cancer mouse xenograft (left, human brain cancer cells grown in a mouse brain), brain cancer cells cultured by 3D magnetic levitation for 48 h. (middle), and cells cultured on a glass slide cover slip (2D, right). The 2D system shows N-cadherin in the cytoplasm and nucleus and notably absent from the membrane, while in the levitated culture and mouse, N-cadherin is clearly concentrated in the membrane, and also present in cytoplasm and cell junctions.
One of the challenges in generating in vivo like cultures or tissue in vitro is the difficulty in co-culturing different cell types. Because of the ability of 3D cell culturing by magnetic levitation to bring cells together, co-culturing different cell types is possible. Co-culturing of different cell types can be achieved at the onset of levitation, by mixing different cell types in before levitation or by magnetically guiding 3D cultures in an invasion assay format.
The unique ability to manipulate cells and shape tissue magnetically offers new possibilities for controlled co-culturing and invasion assays. Co-culturing in a realistic tissue architecture is critical for accurately modeling in vivo conditions, such as for increasing the accuracy of cellular assays as shown in the figure below.
Shown in the picture above is an invasion assay of magnetically levitated multicellular spheroids. Fluorescence images of human glioblastoma (GBM) cells (green; GFP-expressing cells) and normal human astrocytes (NHA) (red; mCherry-labelled) cultured separately and then magnetically guided together (left, time 0). Invasion of GBM into NHA in 3D culture provides a powerful new assay for basic cancer biology and drug screening (right, 12h to 252h).
By facilitating assembly of different populations of cells using the MLM, consistent generation of organoids termed adipospheres capable of simulating the complex intercellular interactions of endogenous white adipose tissue (WAT) can be achieved.
Co-culturing 3T3-L1 pre-adipocytes in 3D with murine endothelial bEND.3 cells creates a vascular-like network assembly with concomitant lipogenesis in perivascular cells. See figure below.
In addition to cell lines, WAT organogenesis can be simulated from primary cells.
Adipocyte-depleted stromal vascular fraction (SVF) containing adipose stromal cells (ASC), endothelial cells, and infiltrating leukocyte derived from mouse white adipose tissue (WAT) were cultured in 3D. This revealed organoids striking in hierarchical organization with distinct capsule and internal large vessel-like structures lined with endothelial cells, as well as perivascular localization of ASC.
Upon adipogenesis induction of either 3T3-L1 adipospheres or adipospheres derived from SVF, the cells efficiently formed large lipid droplets typical of white adipocytes in vivo, whereas only smaller lipid droplet formation is achievable in 2D. This indicates intercellular signaling that better recapitulates WAT organogenesis.
This MLM for 3D co-culturing creates adipospheres appropriate for WAT modeling ex vivo and provides a new platform for functional screens to identify molecules bioactive toward individual adipose cell populations. It can also be adopted for WAT transplantation applications and aid other approaches to WAT-based cell therapy.
Using the MagPen™ (a Nano3D Biosciences, Inc. product), organized 3D co-cultures similar to native tissue architecture can be rapidly created. Endothelial cells (PEC), smooth muscle cells (SMC), fibroblasts (PF), and epithelial cells (EpiC) cultured with the Bio-Assembler™ can be sequentially layered in a drag-and-drop manner to create bronchioles that maintain phenotype and induce extracellular matrix formation.
Listed below are the cell types (primary and cell lines) that have been successfully cultured by the magnetic levitation method. The second table is the same but with images included. More images are available at Nano3D Biosciences, Inc.
Same table as above, but with images.
| 36845407 | https://en.wikipedia.org/wiki?curid=36845407 |
Natural_sciences | Gu Yidong
Gu Yidong (; also known as Yih-Tong Ku, 1903–1996) was a Chinese chemist, considered a founder of inorganic chemistry in China. He was an academician and founding member of the Chinese Academy of Sciences. Gu received his Ph.D in organic chemistry from University of Chicago in 1935.
| 36877348 | https://en.wikipedia.org/wiki?curid=36877348 |
Natural_sciences | Malcolm Steinberg
Malcolm Steinberg (June 1, 1930 - February 7, 2012) was an American biologist who proposed the differential adhesion hypothesis as a mechanism explaining cell sorting during embryogenesis and cancer.
Steinberg proposed that when cells form distinct tissues, specific cell-cell adhesion between cells from the same tissue can drive the separation. He further proposed that a difference in level of cell adhesion molecules expression between two cell types was sufficient to drive the separation.
Steinberg pioneered work in characterizing the physical properties of cells and tissues. He proposed that cell-cell adhesion drives tissue rounding up and, comparing tissues to liquids, he proposed that tissues have a surface tension. To measure tissue surface tension, he participated in building a compression device for rounded tissues.
Steinberg completed his BS at Amherst College in 1952, his PhD in zoology at the University of Minnesota in 1956, was a professor of biology at Johns Hopkins University from 1958 to 1966, and transferred to Princeton University in 1966, becoming professor emeritus in 2005.
| 36899008 | https://en.wikipedia.org/wiki?curid=36899008 |
Natural_sciences | Willow water
Willow water is a biological method to extract the rooting hormones indolebutyric acid (IBA) and salicylic acid (SA), that are present in sufficient quantities in the willow ("Salix") trees to extract as a liquid that stimulates root growth.
| 36907131 | https://en.wikipedia.org/wiki?curid=36907131 |
Natural_sciences | Flux (biology)
In general, flux in biology relates to movement of a substance between compartments. There are several cases where the concept of flux is important.
Flux is the net movement of particles across a specified area in a specified period of time. The particles may be ions or molecules, or they may be larger, like insects, muskrats or cars. The units of time can be anything from milliseconds to millennia. Flux is not the same as velocity or speed nor is it the same as density or concentration. Movement itself is not enough.
| 36911458 | https://en.wikipedia.org/wiki?curid=36911458 |
Natural_sciences | August Wilhelm Malm
August Wilhelm Malm (23 July 1821 in Gothenburg – 5 March 1882) was a Swedish zoologist.
August Wilhelm Malm was the first Director of Göteborgs Naturhistoriska Museum.
Partial list
| 36948649 | https://en.wikipedia.org/wiki?curid=36948649 |
Natural_sciences | Kaigas
The Kaigas glaciation was a hypothesized snowball earth event in the Neoproterozoic Era, preceding the Sturtian glaciation. Its occurrence was inferred based on the interpretation of Kaigas Formation conglomerates in the stratigraphy overlying the Kalahari Craton as correlative with pre-Sturtian Numees formation glacial diamictites. However, the Kaigas formation was later determined to be non-glacial, and a Sturtian age was assigned to the Numees diamictites. Thus, there is no longer any evidence for a Neoproterozoic glaciation prior to the Sturtian snowball earth event.
| 36951734 | https://en.wikipedia.org/wiki?curid=36951734 |
Natural_sciences | Hiroshige Koyama
Hiroshige Koyama (1937–2016) was a Japanese botanist specialist of Asteraceae.
| 36953004 | https://en.wikipedia.org/wiki?curid=36953004 |
Natural_sciences | MinutePhysics
Minute Physics is an educational YouTube channel created by Henry Reich in 2011. The channel's videos use whiteboard animation to explain physics-related topics in approximately one minute. , the channel has more than 4 million subscribers.
Videos from Minute Physics have been featured on "PBS NewsHour", "Huffington Post", "NBC", and "Gizmodo". Minute Physics is also a channel that is able to be viewed through "YouTube EDU".
The most popular Minute Physics video, with more than 11 million views, explores the irresistible force paradox. Reich also has uploaded a series of three videos explaining the Higgs Boson. In March 2020 Reich produced a video that explained exponential projection of statistics as data is being collected, using the evolving record related to COVID-19 data.
Minute Physics has collaborated with Vsauce, as well as the director of the Perimeter Institute for Theoretical Physics, Neil Turok, and Destin Sandlin of Smarter Every Day. Minute Physics also has made two videos that were narrated by Neil deGrasse Tyson and one video narrated by Tom Scott. The channel also collaborated with physicist Sean M. Carroll in a five-part video series on time and entropy and with Grant Sanderson on a video about a lost lecture of physicist Richard Feynman, as well as a video about Bell's Theorem.
Minute Physics also is available to download as a podcast on iTunes.
In October 2011, Reich started a second channel, Minute Earth. The channel features a similar style to his Minute Physics videos, with a focus on the physical properties and phenomena that make up and occur on Earth.
| 36970075 | https://en.wikipedia.org/wiki?curid=36970075 |