Anne-Claude Gingras

Anne-Claude Gingras is a senior investigator at Lunenfeld-Tanenbaum Research Institute, and a professor in the department of molecular genetics at the University of Toronto. She is an expert in mass spectrometry based proteomics technology that allows identification and quantification of protein from various biological samples.
Biography.
Gingras was born on Île d'Orléans, Quebec. She earned her undergraduate degree at Université Laval in Quebec. She completed her PhD in biochemistry at McGill University in Montreal, studying how 4E-BP1 regulated translation initiation, under the mentorship of Nahum Sonenberg. After graduating in 2001, she began postdoctoral research in Seattle at the Institute for Systems Biology in the lab of Ruedi Aebersold, where she studied proteomics for three years.
In 2005, Gingras moved to Toronto and joined the Lunenfeld-Tanenbaum Research Institute, and in 2006 began teaching at the University of Toronto in the department of molecular genetics.
Career.
Gingras research focuses on the development of experimental and bioinformatics approaches for functional proteomics, with a focus on protein-protein and proximity interactions. She applies these tools to the study of signaling pathways in health and disease and in mapping the physical organization of the dynamic proteome. Some of her work focuses on the consequence of disease-associated mutations on the interactions established by proteins.
In addition to proteomics, Gingras laboratory has interest in studying human protein phosphatase and their systematic interactions and has now expanded into the field of systems biology.
Achievements and awards.
Gingras has published > 200 articles that have been cited > 35,000 times (Google Scholar; Feb 2020). In 2011, Gingras was named one of Canada's Top 100 Most Powerful Women. In 2015, Gingras was elected a fellow of the Royal Society of Canada. Her work on interaction proteomics, was awarded, alongside John Yates, the Discovery Award in Proteomics from the Human Proteome Organization (2019). She also received the Jeanne Manery Fisher Memorial Lecture award at the 2019 meeting of the Canadian Society for Molecular Biosciences.


Marcel Kuntz

Marcel Kuntz is a French plant biotechnologist who is a Research Director in the Laboratoire de Physiologie Cellulaire Végétale (Laboratory of Plant and Cell Physiology) at the Centre National de la Recherche Scientifique (National Centre for Scientific Research) in Grenoble, France. He is known for his criticisms of the ways that the French government and popular media have exaggerated the risks associated with genetically modified foods. He has documented how public perception of the risks of such foods has diverged significantly from the conclusions that scientists have reached on the topic. He was a recipient of the Médaille d'Or (Gold Medal) from the Académie d'Agriculture (French Academy of Agriculture) in 2017.


Deltorphin

Deltorphin, also known as deltorphin A and dermenkephalin, is a naturally occurring, exogenous opioid heptapeptide and thus, exorphin, with the amino acid sequence Tyr--Met-Phe-His-Leu-Met-Asp-NH2. Along with the other deltorphins (such as deltorphin I and deltorphin II) and the dermorphins, deltorphin is endogenous to frogs of the genus "Phyllomedusa" such as "P. bicolor" and "P. sauvagei" where it is produced in their skin, and is not known to occur naturally in any other species. Deltorphin is one of the highest affinity and most selective naturally occurring opioid peptides known, acting as a very potent and highly specific agonist of the δ-opioid receptor.
Deltorphins have an unusually high blood–brain barrier penetration rate. The nonselective opiate antagonist naloxone inhibits deltorphin uptake by brain microvessels, but neither the selective δ-opioid antagonist naltrindole nor a number of opioid peptides with different affinities for δ- or μ-opioid receptors compete with deltorphins for the transport.


Don Chaffin

Don Chaffin (born 1939) is an American engineer currently the R. G. Snyder Distinguished University Professor Emeritus at University of Michigan and an Elected Fellow to the American Institute for Medical and Biological Engineering, American Industrial Hygiene Association, Society of Automotive Engineers, National Academy of Engineering, American Association for the Advancement of Science, Ergonomics Society, Human Factors and Ergonomics Society.


Nathaniel Meserve

Nathaniel Meserve (1704–1758) was an American shipbuilder.
Meserve was born in Portsmouth, New Hampshire, to Clement Maserve and his wife Elizabeth Jones.
On December 16, 1725, aged 21, he married Jane Libby and together they had ten children. Nathaniel Meserve would become a shipwright in his native Portsmouth, a hub of early American shipbuilding.
During King George's War Nathaniel was a lieutenant colonel in the New Hampshire Militia regiment at the 1745 capture of Fortress Louisbourg on Cape Breton Island. His shipbuilding experience allowed him to build sleds to transport the cannon over the marshy ground. In 1749 he was hired by the Royal Navy to build a 50 gun warship HMS "America" at his shipyard. During the French and Indian War Colonel Meserve led the New Hampshire Provincial Regiment in 1756 to Fort Edward New York and in 1757 to garrison Halifax, Nova Scotia.
In 1758 Col. Nathaniel Meserve was with General Amherst in another attack on Fortress Louisbourg because of his service in the 1745 capture of the fort. Here he contracted smallpox and died along with his eldest son.


Methylbutyltryptamine

MBT, or "N"-methyl-"N"-butyltryptamine, is a lesser-known psychedelic drug. MBT was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), the minimum dosage is listed as 250-400 mg, and the duration listed as 4–6 hours. MBT produces a heavy body load with dehydration, and causes visuals similar to those of DMT. Very little data exists about the pharmacological properties, metabolism, and toxicity of MBT.
MSBT.
TiHKAL mentions that a structural isomer of MBT exists, with the butyl group attached at the nitrogen atom. It is known as "N-s"-butyl-"N"-methyltryptamine, or MSBT. However, little is known about its psychoactivity.


Ibrahim Shekarau

Ibrahim Shekarau (born November 5, 1955) was a former Nigerian minister of education and two-term Governor of Kano State in Nigeria. He was elected in April 2003 and reelected in April 2007. He is a member of the All Progressive Congress (APC). He was one of the candidates who aspired to become president in the Nigerian general elections of 2011.
Early life and education.
Shekarau was born in the Kurmawa quarters of Kano, the son of a police officer. He was educated at Gidan Makama Primary School (1961–1967), then at Kano Commercial College (1967–1973) and finally at Ahmadu Bello University, Zaria (1973–1977) where he received a Degree in Mathematics/Education.
After finishing his Degree, he went into the civil service. Later on, he started his career as a Mathematics teacher at Government Technical College, Wudil in 1978. Two years later he became Principal at Government Day Junior Secondary School, Wudil. In 1980, he was transferred to Government Secondary School, Hadejia, then to Government College Birnin Kudu in 1986, then to Government Secondary School, Gwammaja and then to Rumfa College in March 1988, all as the school's principal.
Career.
Shekarau became Deputy Director of Education in charge of Bichi Zonal Education Area in 1992. One year later, he was promoted to Director Planning, Research and Statistics in Ministry of Education. Two years later, he became Director General (Permanent Secretary), Ministry of Education and Youth Development.
In January 1995, Shekarau was transferred to Ministry of Water Resources, Rural and Community Development, then back to Ministry of Education in January – May 1997 before he was asked to moved to General Service Directorate of the Cabinet Office, all as Permanent Secretary. By February 2000, he was on the move again to Civil Service Commission, where he stayed for only four months before the civil service commission under Ado Gwaram Government sent him to the State College of Arts, Science and Remedial Studies (CASRS) as Chief lecturer (Mathematics) at the Department of Physical Sciences, in May 2000. Shekarau remained in this post for 17 months before he voluntarily retired from the services of Kano State Civil Service on 2 October 2001. Some time after quitting his post as Chief Lecturer, he decided to work as a secretary to businessman Aminu Dantata. He was employed under Dantata until he became a contender in Kano State's 2003 gubernatorial elections.
Governorship.
As Governor, Shekarau opposed polio vaccination campaigns on the grounds that they are actually attempts to make Muslim women infertile. The World Health Organization denied this.
He was the driving force behind the creation of the local religious police, the "Hisbah Guard", which enforces Sharia law.
Shekarau initiated some large scale development projects in Kano State. He also hosted some world leaders like the former German Chancellor Schroeder, Prince Charles, among others. The Emir of Kano, Alhaji Ado Bayero conferred on him, the title of Sardauna of Kano, now of the leading emirate councillors.
Presidential bid.
Governor Ibrahim Shekarau was one of the candidates for the Nigerian presidential elections of 2011.


Melanocyte-inhibiting factor

Melanocyte-inhibiting factor (also known as Pro-Leu-Gly-NH2, Melanostatin, MSH release–inhibiting hormone or MIF-1) is an endogenous peptide fragment derived from cleavage of the hormone oxytocin, but having generally different actions in the body. MIF-1 produces multiple effects, both blocking the effects of opioid receptor activation, while at the same time acting as a positive allosteric modulator of the D2 and D4 dopamine receptor subtypes, as well as inhibiting release of other neuropeptides such as alpha-MSH, and potentiating melatonin activity.
This complex mix of actions produces a profile of antidepressant, nootropic, and anti-Parkinsonian effects when MIF-1 is administered, and it has been investigated for various medical uses. MIF-1 is unusually resistant to metabolism in the bloodstream, and crosses the blood–brain barrier easily, though it is poorly active orally and is usually injected. Several other closely related peptides with important actions in the body include Tyr-MIF-1 and endomorphin-1 and -2.


Heat shock protein 70 (Hsp70) internal ribosome entry site (IRES)

The heat shock protein 70 (Hsp70) internal ribosome entry site (IRES) is an RNA element that allows cap independent translation during conditions such as heat shock and stress. It has been shown that the 216 nucleotide long 5' UTR contains internal ribosome entry site activity.


Contagious (novel)

Contagious is a science fiction thriller novel by Scott Sigler. It is the sequel to Sigler's "Infected", and like its predecessor was released in both podcast and print versions.
Plot summary.
Perry Dawsey and Margaret Montoya attempt to stop an alien infestation of "hatchlings". Dawsey, former Michigan linebacker, has survived the events in "Infected", but remains telepathically linked to the aliens. His insight into the aliens' behavior helps the government hunt them down. Dawsey is forced to participate.
Reception.
Critical reception for "Contagious" was mostly positive, with author J. C. Hutchins writing that the book "stayed on target, accelerated, and exceeded my expectations". TOR.com also praised the book, stating that it was "gripping, horrifying, and manages to tie several separate plot threads together effortlessly" while criticizing the portrayal of some of the characters. Bookreporter and Monsters and Critics both positively reviewed the book, with Bookreporter calling it a "don't miss."


Diethyltryptamine

DET, also known under its chemical name "N","N"-diethyltryptamine and as T-9, is a psychedelic drug closely related to DMT and 4-HO-DET. However, despite its structural similarity to DMT, its activity is induced by an oral dose of around 50–100 mg, without the aid of MAO inhibitors, and the effects last for about 2–4 hours.
Chemistry.
DET is an analogue of the common tryptamine hallucinogen N,N-Dimethyltryptamine or DMT.
Pharmacology.
The mechanism of action is thought to be serotonin receptor agonism, much like other classic psychedelics.
DET is sometimes preferred over DMT because it can be taken orally, whereas DMT cannot. This is because the enzyme monoamine oxidase degrades DMT into an inactive compound before it is absorbed. To overcome this, it must be administered in a different manner, i.e. intravenously, intramuscularly, by inhalation, by insufflation, rectally, or ingested along with an inhibitor of monoamine oxidase. Because DET has ethyl groups attached to its nitrogen atom, monoamine oxidase is unable to degrade it. This is also true for many other tryptamines with larger nitrogen substituents.
Biochemistry.
Although DET is a synthetic compound with no known natural sources, it has been used in conjunction with the mycelium of "Psilocybe cubensis" to produce the synthetic chemicals 4-PO-DET (Ethocybin) and 4-HO-DET (Ethocin), as opposed to the naturally occurring 4-PO-DMT (Psilocybin) and 4-HO-DMT (Psilocin). Isolation of the alkaloids resulted in 3.3% 4-HO-DET and 0.01-0.8% 4-PO-DET.
Psychosis model.
Early studies of DET as well as other psychedelics were mainly focused on their presumed psychotomimetic properties. Researchers theorized that abnormal metabolites of endogenous chemicals such as tryptamine, serotonin, and tryptophan could be the explanation for mental disorders such as schizophrenia, or psychosis. With the progression of science and pharmacological understanding, this belief has been dismissed by most researchers.
Legal status.
Internationally DET is a Schedule I drug under the Convention on Psychotropic Substances.
Australia.
DET is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.


Chromatium

Chromatium is a genus of photoautotrophic Gram-negative bacteria which are found in water. The cells are straight rod-shaped or slightly curved. They belong to the purple sulfur bacteria and oxidize sulfide to produce sulfur which is deposited in intracellular granules of the cytoplasm.


Didemnin

Didemnins are cyclic depsipeptide compounds isolated from a tunicate (ascidian, or sea-squirt) of the genus "Trididemnum" (family of Didemnidæ) that were collected in the Caribbean Sea. They were first isolated in 1978 at the University of Illinois.
Although more than nine didemnins (didemnins A-E, G, X and Y) have been isolated from the extract of "Trididemnum solidum", didemnin B is the one that possesses the most potent biological activities. It is a strong antiviral agent against both DNA and RNA viruses such as herpes simplex virus type 1, a strong immunosuppressant that shows some potential in skin graft and is also very cytotoxic. It shows strong activity against murine leukemia cells. Large amounts of didemnin B were chemically synthesized and it was advanced to clinical trials by the National Cancer Institute. It has completed phase II human clinical trials against adenocarcinoma of the kidney, advanced epithelial ovarian cancer, and metastatic breast cancer. Unfortunately, the compound exhibited high toxicity through a high incidence of anaphylactic reactions in patients and trials were terminated.
The didemnin analog plitidepsin was in phase II clinical trials as of 2003.


CK Life Sciences

CK Life Sciences International (Holdings) Inc. (), or CK Life Sciences, is a subsidiary of CK Hutchison Holdings. It is engaged in research and development, commercialization, marketing and sale of biotechnology products. The chairman is Mr. Victor Li, the elder son of Mr. Li Ka-shing, the chairman of Cheung Kong Holdings.
It was established in 2000 and listed on the Hong Kong Stock Exchange via Growth Enterprise Market in 2002 (Former stock code: ). It was transferred to Main Board of the Hong Kong Stock Exchange in 2008.
CK Life Sciences has operations in Australia, and in 2012 acquired an Australian salt company (Cheetham Salt) as part of its expansion into the agricultural sector.


Native chemical ligation

Native chemical ligation or NCL is an important extension of the chemical ligation field, a concept for constructing a large polypeptide formed by the assembling of two or more unprotected peptides segments. Especially, NCL is the most powerful ligation method for synthesizing native backbone proteins or modified proteins of moderate size ("i.e.", small proteins< 200 AA).
Reaction.
In native chemical ligation, the thiol group of an N-terminal cysteine residue of an unprotected peptide 2 attacks the C-terminal thioester of a second unprotected peptide 1 in an aqueous buffer at pH 7.0, 20 °C<T<37 °C. This reversible transthioesterification step is chemoselective and regioselective and leads to form a thioester intermediate 3. This intermediate rearranges by an intramolecular "S,N-acyl shift" that results in the formation of a native amide ('peptide') bond 4 at the ligation site (scheme 1).
Remarks :
NCL reaction is catalyzed by in situ transthioesterification with thiol additives. The most common thiol catalysts to date have been either a mixture of thiophenyl, 4-mercaptophenylacetic acid (MPAA), or 2-mercaptoethanesulfonate (MESNa). (ref)
The main property of the NCL method is the reversibility of the first step, the thiol(ate)–thioester exchange reaction. Native chemical ligation is exquisitely regioselective because that thiol(ate)–thioester exchange step is freely reversible in the presence of an exogenous thiol added as catalyst. The high yields of final ligation product obtained, even in the presence of internal Cys residues in either/both segments, is the result of the irreversibility, under the reaction conditions used, of the second (S-to-N acyl shift) amide-forming step.
No side-products are formed from reaction with the other functional groups present in either peptide segment (acids or basics amino groups, phenolic hydroxyls, etc.).
Historical context.
In 1953, Theodor Wieland and coworkers discovered the chemical foundation for this reaction, when the reaction of valine-thioester and cysteine amino acid in aqueous buffer was shown to yield the dipeptide valine-cysteine. The reaction proceeded through the intermediacy of a thioester containing the sulfur of the cysteine residue. Wieland's work led to the 'active ester' method for making protected peptide segments in conventional solution synthesis in organic solvents.
In the 1990s, Stephen Kent and coworkers at The Scripps Research Institute independently developed "Native Chemical Ligation", the first practical method to ligate large unprotected peptide fragments.
Properties.
Native chemical ligation is carried out in aqueous solution and frequently gives near-quantitative yields of the desired ligation product. The challenge lies in the preparation of the necessary unprotected peptide-thioester building block. Peptide-thioesters are usually prepared by Boc chemistry SPPS; a thioester-containing peptide cannot be synthesized using a nucleophilic base, thus disfavoring Fmoc chemistry. Fmoc chemistry solid phase peptide synthesis techniques for generating peptide-thioesters are known; they make use of modifications of the Kenner 'safety catch' linker. In making peptide segments for use in native chemical ligation, protecting groups that release aldehydes or ketones should be avoided since these may cap the N-terminal cysteine. For the same reason, the use of acetone should be avoided, particularly prior to lyophilization and in washing glassware.
A feature of the native chemical ligation technique is that the product polypeptide chain contains cysteine at the site of ligation. For some proteins, homocysteine can be used and methylated after ligation to form methionine, although side reactions can occur in this alkylation step. The cysteine at the ligation site can also be desulfurized to alanine; more recently, other beta-thiol containing aminoacids have been used for native chemical ligation, followed by desulfurization. Alternatively, thiol-containing ligation auxiliaries can be used that mimic an N-terminal cysteine for the ligation reaction, but which can be removed after synthesis. The use of thiol-containing auxiliaries is not as effective as ligation at a Cys residue. Native chemical ligation can also be performed with an N-terminal selenocysteine residue.
The payoff in the native chemical ligation method is that coupling long peptides by this technique is in many cases nearly quantitative and provides synthetic access to large peptides and proteins otherwise impossible to make, due to length or decoration by post-translational modification. Native chemical ligation forms the basis of modern chemical protein synthesis, and has been used to prepare numerous proteins and enzymes by total chemical synthesis.
Polypeptide C-terminal thioesters produced by recombinant DNA techniques can be reacted with an N-terminal Cys containing polypeptide by the same native ligation chemistry to provide very large semi-synthetic proteins. Native chemical ligation of this kind using a recombinant polypeptide segment is known as Expressed Protein Ligation. Similarly, a recombinant protein containing an N-terminal Cys can be reacted with a synthetic polypeptide thioester. Thus, native chemical ligation can be used to introduce chemically synthesized segments into recombinant proteins, regardless of size.
Polypeptide C-terminal thioesters can also be produced "in situ", using so-called "N,S"-acyl shift systems. "Bis"(2-sulfanylethyl)amido group, also called SEA group, belongs to this family. Polypeptide C-terminal "bis"(2-sulfanylethyl)amides (SEA peptide segments) react with Cys peptide to give a native peptide bond as in NCL. This reaction, which is called SEA Native Peptide Ligation, is a useful extension of Native Chemical Ligation.
Size limitation.
NCL has been proven to be a convenient method for the chemical synthesis of proteins well over 100 amino acids in length, as demonstrated on the 166-amino-acid polypeptide chain of the synthetic variant of erythropoietin and the 203 amino acid HIV-1 protease.


Sulfhydrogenase

In enzymology, a sulfhydrogenase (), also known as sulfur reductase, is an enzyme that catalyzes the reduction of elemental sulfur or polysulfide to hydrogen sulfide using hydrogen as electron donor.
This enzyme belongs to the family of oxidoreductases. The systematic name of this enzyme class is H2:polysulfide oxidoreductase.


June Lindsey

June M. Lindsey (née Broomhead) (born June 7, 1922) is a British-Canadian physicist. Whilst working on X-ray crystallography at the University of Cambridge, Lindsey was influential in the elucidation of the structure DNA. She solved the structures of the purines, adenine and guanine. Her depiction of intramolecular hydrogen bonds in adenine crystals was central to Watson and Crick's elucidation of the double helical structure of DNA.
Education and early career.
Lindsey joined the University of Cambridge in 1941. She completed her degree in 1944, but World War II forced her to leave her research career. She was encouraged to become a teacher, and spent two years teaching science in a school. She returned to Cambridge in 1946. She completed undergraduate courses at Newnham College, but Cambridge did not give women undergraduate degrees until 1948. She was awarded her doctorate in 1948. She solved the crystal structure of a complex of adenine and guanine. She delineated the shape and dimensions of the two nitrogenous subunits of DNA. She proposed that complementary nucleobases are bound together by hydrogen bonds, work that was expanded by Bill Cochran. Her research, particularly the prediction of hydrogen bonds, was used by Watson and Crick to determine the structure of DNA. They created cardboard models based on the dimensions from Lindsey's crystal structures. Francis Crick worked opposite Lindsey at the University of Cambridge. They did not recognise the contributions of Lindsey in their discovery of the .
Career.
After graduating, Lindsey moved to the University of Oxford, where she worked as a postdoctoral scholar with Dorothy Hodgkin on Vitamin B12. Lindsey moved to Canada in 1951. Before she left, Lawrence Bragg wrote to her requesting that she join him working on experimental and theoretical crystallography. In a letter, he wrote: “We badly need your hands to tackle knotty crystallographic problems, both experimental and theoretical. I wish all these things had come up while you were still with us; they would have been just in your line.” She worked at the National Research Council on the structure of codeine and morphine. Her husband, George Lindsey, was stationed in Montreal.
Lindsey left her career in crystallography to look after her two children, Jane and Robin. They moved to Italy on a NATO mission in 1961. Today, Robin is a Professor of Business Management at the University of British Columbia and Jane is a biostatistician at the Harvard T.H. Chan School of Public Health. Lindsey collected her bachelor's degree in 1998, 50 years after completing it.
Discovery.
Alex MacKenzie, a pediatrician at the Children's Hospital of Eastern Ontario in Ottawa, who knew Lindsey as friend of his mother in law inquired of her work at his mother in law's 90th birthday party. She told him about her 1940s work on crystallography, which inspired him to research her scientific contributions. MacKenzie was amazed by what he found and did not want her work to go unnoticed; it is "something we should shout from the mountaintops".


AH-494

AH-494 is a potent and selective, water-soluble full agonist at the 5HT7 serotonin receptor. It is a close derivative of the known chemical probe 5-Carboxamidotryptamine, as well as of the more lipophilic indole-imidazoles: AGH-107 and AGH-192. It has been shown to exhibit favorable ADMET profile in in vitro assays.


List of Inhumans

The following is a list of known fictional characters who are Inhumans, a race of superhumans appearing in Marvel Comics and media inspired by them.
Known Inhumans.
Inhuman Royal Family.
The Inhuman Royal Family are the ruling class of the Inhumans. Among the members of the Inhuman Royal Family are:
Inhuman Royal Guards.
The Inhuman Royal Guards are a group of Inhumans that are responsible for protecting the Inhuman Royal Family. Among its members are:
Genetic Council.
The Genetic Council is a group of Inhumans who are charged with making decisions concerning the use of the Terrigen Mists and the fate of the Inhumans. Among the known members are:
Inhuman allies of Maximus.
The following Inhumans are allies of Maximus the Mad:
Crimson Cadre.
The Crimson Cadre are the Inhumans' personal strike force led by General Ator. Among its members are:
Dark Riders.
The Dark Riders are a group of Mutants and Inhumans drafted by Apocalypse. Among its Inhuman members are:
Universal Inhumans.
The Inhumans and the Kree have experimented on some Centaurians, Dire Wraiths, Kymellians, and Badoon so that when Black Bolt is found, he can lead them into a new era. Besides the Inhuman Royal Family, among the members of the Universal Inhumans are:
Light Brigade.
A special team of Universal Inhumans who rescued Human Torch from Annihilus. Among the members of the Light Brigade are:
Other Inhumans.
Unless stated otherwise, it can be assumed that the listed Inhumans are residing in Attilan. Among the Inhumans listed here are:
Inhuman Hybrids (NuHumans).
In the wake of "Infinity", it is revealed that tribes of Inhumans have existed in secret around Earth and that they had mated with humans, many eventually finding their way into modern society, without knowing their past, producing Inhuman/human hybrids. "Inhumanity" deals with the aftermath of this revelation.
Super-Inhumans.
In the wake of "Death of the Inhumans", it is revealed that the Kree had created a new race of Inhumans which was dubbed as Super-Inhumans. This new race was engineered from birth to possess almost all of their Inhuman abilities and none of their humanity, something the Kree thought to be problematic.
Vox – The first and currently the only member of this race, he is described as the "voice and the wrath of the gods and the full-throated scream of the Kree Empire". Besides his great powers, he also wields a scythe consisting of a handle and blade made of an unknown kind of red energy and a small sharp dagger. His costume also possess a similar resemblance to that of Ahura Boltagon from the "Earth X" reality. Vox is later revealed to be actually a program designed by the Kree which is forcefully imprinted on some selected Inhumans. When the program was activated those who were selected would loose all of their identities and free will and are genetically transformed into Vox, obedient deadly hunters. Black Bolt ended up wiping out the entire Vox army, but not without some Kree escaping the slaughter. The program was apparently used in the Supreme Intelligence as Vox reappeared now wearing an emerald costume instead of the black one with crimson highlights, and calling himself as Vox Supreme. He fights Carol Danvers and forces her to kill the Avengers.
Other version of Inhumans.
Inhumans of Earth-691.
In an alternate future of the Marvel Universe inhabited by the Guardians of the Galaxy, some new Inhumans are present. Among these Inhumans are:
Marvel Cinematic Universe.
Appearing in Marvel's Inhumans.
Marvel Television has confirmed the Inhuman Royal Family and other notable Inhumans from the comics will appear in "Marvel's Inhumans". They consist of:
Appearing in Agents of S.H.I.E.L.D..
The TV series Marvel's Agents of S.H.I.E.L.D. has introduced Inhumans most of which were created specifically for the show.


Muscle-type nicotinic receptor

The muscle-type nicotinic receptor is a type of nicotinic acetylcholine receptor consisting of the subunit combination (α1)2β1δε (adult receptor) or (α1)2β1δγ (fetal receptor). These receptors are found in neuromuscular junctions, where activation leads to an excitatory postsynaptic potential (EPSP), mainly by increased Na+ and K+ permeability.
Activation.
Tetraethylammonium (TEA) is a molecule found to be a weak agonist of the muscle‐type nicotinic receptor. Since receptor activation occurs as isolated bursts, it has been proposed that the receptors have a very low channel‐opening rate constant when bound to TEA.
Inhibition.
Lidocaine, a local anesthetic, has multiple inhibitory actions on the receptor and analysis of the structure of lidocaine has identified the presence of a hydrophobic aromatic ring and a hydrophilic terminal amine. Diethylamine (DEA), a molecule that mimics the hydrophilic moiety of lidocaine by way of a positively charged amine, has been found to block the channel when the receptor is open restricting the flow of Na+ and K+ ions. 2,6-Dimethylaniline (DMA), a molecule that mimics the hydrophobic moiety of lidocaine, has been found to bind the receptor at inter-subunit crevices of the trans-membrane spanning domain thereby causing non-competitive inhibition and restricting the channel from opening.
Benzocaine and tetracaine are also local anesthetics that have an inhibitory effect on the muscle‐type nicotinic receptor. Benzocaine is a permanently uncharged species that inhibits the receptor by plugging the pore of the opened channel. Tetracaine is a permanently positively charged species. It can bind to the receptor at different sites in both the open and closed conformations. Both of these local anesthetics enhance nAChR desensitization.


MicA RNA

The MicA RNA (also known as SraD) is a small non-coding RNA that was discovered in "E. coli" during a large scale screen. Expression of SraD is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well.
Function.
This RNA binds the Hfq protein and regulates levels of gene expression by an antisense mechanism. It is known to target the OmpA gene in "E. coli" and occludes the ribosome binding site. Under conditions of envelope stress, micA transcription is induced. MicA, RybB RNA and MicL RNA transcription is under the control of the sigma factor sigma(E). In "E.coli", SraD also interacts in "cis" and "trans" with the mRNA species, "luxS", "ompA a"nd "phoP", respectively. This observation describes MicA to be the first known sRNA to carry out antisense regulation in both structural configurations. MicA is known to interact with the mRNA encoding the quorum sensing synthase homolog, LuxS in E.coli and both RNAs are processed by the double stranded RNA endonuclease, RNase III. Based on its conservation, this is presumably the case in close relatives and may serve as a long elusive link between envelope stress and quorum sensing.
The PhoPQ two-component system is repressed by MicA.
The RNA presumably pairs with the ribosomal binding site of phoP mRNA, thereby inhibiting translation.
This links micA to cellular processes such as Mg(2+) transport, virulence, LPS modifications and resistance to antimicrobial peptides.
In "S. typhimurium" MicA has been shown to be involved in biofilm formation. It is observed that the "luxS" mutant biofilm formation process is found to be dependent on MicA in cases where the gene's coding region is deleted, however, it is still not known to what extent MicA is involved in this mechanism.
Site directed mutagensis has been used to construct mutated forms of MicA forms in order to investigate the RNA determinants important to its stability and function. Each 'domain' investigated ( 5′linear domain, the structured region with two stem-loops, the A/U-rich sequence and the 3′ poly(U) tail) was altered without affecting the overall secondary structure of MicA however, each 'domain' was found to have a different impact on stability and the ability of MicA to regulate its multiple targets.


Ketogenesis

Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others. (In rare metabolic diseases, insufficient gluconeogenesis can cause excessive ketogenesis and hypoglycemia, which may lead to the life-threatening condition known as non-diabetic ketoacidosis.)
Ketone bodies are not obligately produced from fatty acids; rather a meaningful amount of them is synthesized only in a situation of carbohydrate and protein insufficiency, where only fatty acids are readily available as fuel for their production.
Production.
Ketone bodies are produced mainly in the mitochondria of liver cells, and synthesis can occur in response to an unavailability of blood glucose, such as during fasting. Other cells, e.g. human astrocytes, are capable of carrying out ketogenesis, but they are not as effective at doing so. Ketogenesis occurs constantly in a healthy individual. Ketogenesis in healthy individuals is ultimately under the control of the master regulatory protein AMPK, which is activated during times of metabolic stress, such as carbohydrate insufficiency. Activation in the liver inhibits lipogenesis, promotes fatty acid oxidation, switches off acetyl-CoA carboxylase, turns on malonyl-CoA decarboxylase, and consequently induces ketogenesis. Ethanol is a potent AMPK inhibitor and therefore can cause significant disruptions in the metabolic state of the liver, including halting of ketogenesis, even in the context of hypoglycemia.
Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen. It can also take place when there is insufficient insulin (e.g. in type 1 (and less commonly type 2) diabetes), particularly during periods of "ketogenic stress" such as intercurrent illness.
The production of ketone bodies is then initiated to make available energy that is stored as fatty acids. Fatty acids are enzymatically broken down in β-oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is further oxidized by the citric acid cycle (TCA/Krebs cycle) and then by the mitochondrial electron transport chain to release energy. However, if the amounts of acetyl-CoA generated in fatty-acid β-oxidation challenge the processing capacity of the TCA cycle; i.e. if activity in TCA cycle is low due to low amounts of intermediates such as oxaloacetate, acetyl-CoA is then used instead in biosynthesis of ketone bodies via acetoacetyl-CoA and β-hydroxy-β-methylglutaryl-CoA (HMG-CoA). Furthermore, since there is only a limited amount of coenzyme A in the liver, the production of ketogenesis allows some of the coenzyme to be freed to continue fatty-acid β-oxidation. Depletion of glucose and oxaloacetate can be triggered by fasting, vigorous exercise, high-fat diets or other medical conditions, all of which enhance ketone production. Deaminated amino acids that are ketogenic, such as leucine, also feed TCA cycle, forming acetoacetate & ACoA and thereby produce ketones. Besides its role in the synthesis of ketone bodies, HMG-CoA is also an intermediate in the synthesis of cholesterol, but the steps are compartmentalised. Ketogenesis occurs in the mitochondria, whereas cholesterol synthesis occurs in the cytosol, hence both processes are independently regulated.
Ketone bodies.
The three ketone bodies, each synthesized from acetyl-CoA molecules, are:
β-Hydroxybutyrate and acetoacetate can pass through membranes easily, and are therefore a source of energy for the brain, which cannot directly metabolize fatty acids. The brain receives 60-70% of its required energy from ketone bodies when blood glucose levels are low. These bodies are transported into the brain by monocarboxylate transporters 1 and 2. Therefore, ketone bodies are a way to move energy from the liver to other cells. The liver does not have the critical enzyme, succinyl CoA transferase, to process ketone bodies, and therefore cannot undergo ketolysis. The result is that the liver only produces ketone bodies, but does not use a significant amount of them.
Regulation.
Ketogenesis may or may not occur, depending on levels of available carbohydrates in the cell or body. This is closely related to the paths of acetyl-CoA:
Insulin and glucagon are key regulating hormones of ketogenesis, with insulin being the primary regulator. Both hormones regulate hormone-sensitive lipase and acetyl-CoA carboxylase. Hormone-sensitive lipase produces diglycerides from triglycerides, freeing a fatty acid molecule for oxidation. Acetyl-CoA carboxylase catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA reduces the activity of carnitine palmitoyltransferase I, an enzyme that brings fatty acids into the mitochondria for β-oxidation. Insulin inhibits hormone-sensitive lipase and activates acetyl-CoA carboxylase, thereby reducing the amount of starting materials for fatty acid oxidation and inhibiting their capacity to enter the mitochondria. Glucagon activates hormone-sensitive lipase and inhibits acetyl-CoA carboxylase, thereby stimulating ketone body production, and making passage into the mitochondria for β-oxidation easier. Insulin also inhibits HMG-CoA lyase, further inhibiting ketone body production. Similarly, cortisol, catecholamines, epinephrine, norepinephrine, and thyroid hormones can increase the amount of ketone bodies produced, by activating lipolysis (the mobilization of fatty acids out of fat tissue) and thereby increasing the concentration of fatty acids available for β-oxidation. Unlike glucagon, catecholamines are capable of inducing lipolysis even in the presence of insulin for use by peripheral tissues during acute stress.
Peroxisome Proliferator Activated Receptor alpha (PPARα) also has the ability to regulate ketogenesis, as it has some control over a number of genes involved in ketogenesis. For example, monocarboxylate transporter 1, which is involved in transporting ketone bodies over membranes (including the blood-brain barrier), is regulated by PPARα, thus affecting ketone body transportation into the brain. Carnitine palmitoyltransferase is also regulated by PPARα, which can affect fatty acid transportation into the mitochondria.
Pathology.
Both acetoacetate and beta-hydroxybutyrate are acidic, and, if levels of these ketone bodies are too high, the pH of the blood drops, resulting in ketoacidosis. Ketoacidosis is known to occur in untreated type I diabetes (see diabetic ketoacidosis) and in alcoholics after prolonged binge-drinking without intake of sufficient carbohydrates (see alcoholic ketoacidosis).
Ketogenesis can be ineffective in people with beta oxidation defects.
Individuals with diabetes mellitus can experience overproduction of ketone bodies due to a lack of insulin. Without insulin to help extract glucose from the blood, tissues the levels of malonyl-CoA are reduced, and it becomes easier for fatty acids to be transported into mitochondria, causing the accumulation of excess acetyl-CoA. The accumulation of acetyl-CoA in turn produces excess ketone bodies through ketogenesis. The result is a rate of ketone production higher than the rate of ketone disposal, and a decrease in blood pH.
There are some health benefits to ketone bodies and ketogenesis as well. It has been suggested that a low-carb, high fat ketogenic diet can be used to help treat epilepsy in children. Additionally, ketone bodies can be anti-inflammatory. Some kinds of cancer cells are unable to use ketone bodies, as they do not have the necessary enzymes to engage in ketolysis. It has been proposed that actively engaging in behaviors that promote ketogenesis could help manage the effects of some cancers.


Human umbilical artery endothelial cells

Human umbilical artery endothelial cells (HUAECs) are cells derived from the endothelium of arteries from the umbilical cord. They are used as a laboratory model system for the study of the function and pathology of endothelial cells (e.g., atherosclerosis). HUAECs have “cobblestone” morphology.


Spt-Ada-Gcn5 acetyltransferase

Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a multicomponent regulator of acetylation. It has been found that this complex is highly conserved between different organisms, such as humans, "Drosophila", and yeast. This 15 subunit complex has been best characterized for its histone acetyltransferase activity (HAT). The acetylating activity has been found to occur in the lysine residues of the N-terminal tails of H3 and H2 histones. It has been found recently that this activity is actually a deubiquitination of a monoubiquitin that occurs in residue Lys 123 of the H2b histone and the acetylation of the H3 histone. The histone acetylation is mediated by the GCN5 histone acetyl transferase, while the deubiquitinating activity is mediated by a deubiquitinating module (DUBm), which is composed of 4 proteins, Ubp8 ubiquitin hydrolase, Sgf11, Sus1, and Sgf73. This DUB module is an independently folding subcomplex that is connected to the C-terminal tail of Sgf 73, Sgf73, as well as Sus1, also have a role in facilitating SAGA complex's role in nuclear export by binding to components of the nuclear pore complex. Even though Ubp8 has ubiquitin specific hydrolase (USP) domain, the protein remains inactive unless it is in complex with the other 3 DUBm proteins.


RNA polymerase II

RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription.
Discovery.
Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, science experimentalists Robert Roeder and William Rutter definitively discovered an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. The finding was obtained by the use of ion-exchange chromatography via DEAE coated Sephadex beads. The technique separated the enzymes by the order of the corresponding elutions, Ι,ΙΙ,ΙΙΙ, by increasing the concentration of ammonium sulfate. The enzymes were named according to the order of the elutions, RNAP I, RNAP II, RNAP IΙI. This discovery demonstrated that there was an additional enzyme present in the nucleoplasm, which allowed for the differentiation between RNAP II and RNAP III.
Subunits.
The eukaryotic core RNA polymerase II was first purified using transcription assays. The purified enzyme has typically 10–12 subunits (12 in humans and yeast) and is incapable of specific promoter recognition. Many subunit-subunit interactions are known.
Assembly.
RPB3 is involved in RNA polymerase II assembly. A subcomplex of RPB2 and RPB3 appears soon after subunit synthesis. This complex subsequently interacts with RPB1. RPB3, RPB5, and RPB7 interact with themselves to form homodimers, and RPB3 and RPB5 together are able to contact all of the other RPB subunits, except RPB9. Only RPB1 strongly binds to RPB5. The RPB1 subunit also contacts RPB7, RPB10, and more weakly but most efficiently with RPB8. Once RPB1 enters the complex, other subunits such as RPB5 and RPB7 can enter, where RPB5 binds to RPB6 and RPB8 and RPB3 brings in RPB10, RPB 11, and RPB12. RPB4 and RPB9 may enter once most of the complex is assembled. RPB4 forms a complex with RPB7.
Kinetics.
Enzymes can catalyze up to several million reactions per second. Enzyme rates depend on solution conditions and substrate concentration. Like other enzymes POLR2 has a saturation curve and a maximum velocity ("V"max). It has a "K"m (substrate concentration required for one-half "V"max) and a "k"cat (the number of substrate molecules handled by one active site per second). The specificity constant is given by "k"cat/"K"m. The theoretical maximum for the specificity constant is the diffusion limit of about 108 to 109 ("M"−1"s"−1), where every collision of the enzyme with its substrate results in catalysis. In yeast, mutation in the Trigger-Loop domain of the largest subunit can change the kinetics of the enzyme.
Bacterial RNA polymerase, a relative of RNA Polymerase II, switches between inactivated and activated states by translocating back and forth along the DNA. Concentrations of [NTP]eq = 10 μM GTP, 10 μM UTP, 5 μM ATP and 2.5 μM CTP, produce a mean elongation rate, turnover number, of ~1 bp (NTP)−1 for bacterial RNAP, a relative of RNA polymerase II.
RNA polymerase II undergoes extensive co-transcriptional pausing during transcription elongation. This pausing is especially pronounced at nucleosomes, and arises in part through the polymerase entering a transcriptionally incompetent backtracked state. The duration of these pauses ranges from seconds to minutes or longer, and exit from long-lived pauses can be promoted by elongation factors such as TFIIS. In turn, the transcription rate influences whether the histones of transcribed nucleosomes are evicted from chromatin, or reinserted behind the transcribing polymerase.
Alpha-Amanitin.
RNA polymerase II is inhibited by α-Amanitin and other amatoxins. α-Amanitin is a highly poisonous substance found in many mushrooms. The mushroom poison has different effects on the each of the RNA Polymerases: I, II, III. RNAP I is completely unresponsive to the substance and will function normally while RNAP III has a moderate sensitivity. RNAP II, however, is completely inhibited by the toxin. Alpha-Amanitin inhibits RNAP II by strong interactions in the enzyme's "funnel", "cleft", and the key "bridge α-helix" regions of the RPB-1 subunit.
Holoenzyme.
RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins.
Part of the assembly of the holoenzyme is referred to as the preinitiation complex, because its assembly takes place on the gene promoter before the initiation of transcription. The mediator complex acts as a bridge between RNA polymerase II and the transcription factors.
Control by chromatin structure.
This is an outline of an example mechanism of yeast cells by which chromatin structure and histone posttranslational modification help regulate and record the transcription of genes by RNA polymerase II.
This pathway gives examples of regulation at these points of transcription:
This refers to various stages of the process as regulatory steps. It has not been proven that they are used for regulation, but is very likely they are.
RNA Pol II elongation promoters can be summarised in 3 classes.
Transcription mechanisms.
CTD of RNA polymerase.
The C-terminus of RPB1 is appended to form the C-terminal domain (CTD). The carboxy-terminal domain of RNA polymerase II typically consists of up to 52 repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. The domain stretches from the core of the RNAPII enzyme to the exit channel, this placement is effective due to its inductions of "RNA processing reactions, through direct or indirect interactions with components of the RNA processing machinery". The CTD domain does not exist in RNA Polymerase I or RNA Polymerase III. The RNA Polymerase CTD was discovered first in the laboratory of C.J.Ingles at the University of Toronto and also in the laboratory of J Corden at Johns Hopkins University during the processes of sequencing the DNA encoding the RPB1 subunit of RNA polymerase from Yeast and Mice respectively. Other proteins often bind the C-terminal domain of RNA polymerase in order to activate polymerase activity. It is the protein domain that is involved in the initiation of transcription, the capping of the RNA transcript, and attachment to the spliceosome for RNA splicing.
Phosphorylation of the CTD domain.
RNA Polymerase II exists in two forms unphosphorylated and phosphorylated, IIA and IIO respectively. The transition between the two forms facilitates different functions for transcription. The phosphorylation of CTD is catalyzed by one of the six general transcription factors, TFIIH. TFIIH serves two purposes: one is to unwind the DNA at the transcription start site and the other is to phosphorylate. The form polymerase IIA joins the preinitiation complex, this is suggested because IIA binds with higher affinity to the TBP (TATA-box binding protein), the subunit of the general transcription factor TFIID, than polymerase IIO form. The form polymerase IIO facilitates the elongation of the RNA chain. The method for the elongation initiation is done by the phosphorylation of Serine at position 5 (Ser5), via TFIIH. The newly phosphorylated Ser5 recruits enzymes to cap the 5' end of the newly synthesized RNA and the "3' processing factors to poly(A) sites". Once the second Serine is phosphorylated, Ser2, elongation is activated. In order to terminate elongation dephosphorylation must occur. Once the domain is completely dephosphorylated the RNAP II enzyme is "recycled" and catalyzes the same process with another initiation site.
Transcription coupled recombinational repair.
Oxidative DNA damage may block RNA polymerase II transcription and cause strand breaks. An RNA templated transcription-associated recombination process has been described that can protect against DNA damage. During the G1/G0 stages of the cell cycle, cells exhibit assembly of homologous recombination factors at double-strand breaks within actively transcribed regions. It appears that transcription is coupled to repair of DNA double-strand breaks by RNA templated homologous recombination. This repair process efficiently and accurately rejoins double-strand breaks in genes being actively transcribed by RNA polymerase II.


Reticuline oxidase

In enzymology, a reticuline oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are (S)-reticuline and O2, whereas its two products are (S)-scoulerine and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on X-H and Y-H to form an X-Y bond with oxygen as acceptor. The systematic name of this enzyme class is (S)-reticuline:oxygen oxidoreductase (methylene-bridge-forming). Other names in common use include BBE, berberine bridge enzyme, berberine-bridge-forming enzyme, and tetrahydroprotoberberine synthase. This enzyme participates in alkaloid biosynthesis i.


Glycerol-3-phosphate cytidylyltransferase

In enzymology, a glycerol-3-phosphate cytidylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are CTP and sn-glycerol 3-phosphate, whereas its two products are diphosphate and CDP-glycerol.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is CTP:sn-glycerol-3-phosphate cytidylyltransferase. Other names in common use include CDP-glycerol pyrophosphorylase, cytidine diphosphoglycerol pyrophosphorylase, cytidine diphosphate glycerol pyrophosphorylase, CTP:glycerol 3-phosphate cytidylyltransferase, and Gro-PCT. This enzyme participates in glycerophospholipid metabolism.
Structural studies.
As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes , , and .


Cetamolol

Cetamolol is a beta adrenergic antagonist, more specifically a β1-adrenergic blocker.


Motilin receptor

Motilin receptor is a G protein-coupled receptor that binds motilin. Motilin in turn is an intestinal peptide that stimulates contraction of gut smooth muscle.


Ida Kraus Ragins

Ida Kraus Ragins, née Kraus (10 October 1894 – September 1985), was a Russian-born American biochemist.
Life and work.
Ida Kraus Ragins was born in the Russian Empire and moved to the United States before 1915. That year she started work as an assistant in quantitative analysis in the Department of Chemistry of the University of Chicago, possibly as a student job, as she received her B.A. in 1918 and her M.S. from the university the following year. Kraus Ragins taught for a year at the Oklahoma College for Women, before returning to Chicago to work on her Ph.D. which she received in 1924. She then worked as an instructor in biochemistry at the university until she became a senior chemist at Cook County Hospital in 1937. Kraus Ragins married Oscar B. Ragins, a physician, the same year that she received her Ph.D. and had her daughter in 1926 and a son in 1929.
Kraus Ragins specialized in protein specificity reactions and amino acids before she moved to Northwestern Medical School in 1946 where she became a senior chemist in experimental medicine. She remained there for only three years before accepting a position at the Chicago College of Osteopathic Medicine as head of the department of biochemistry in 1949. No further information on her life is available.


Charles Boarman (pioneer)

Dr. Charles Boarman (October 28, 1828 – November 22, 1880) was an American pioneer and frontier physician. He was among the original pioneers to settle in present-day Amador County, California, serving as its first county physician from 1863 until 1880, and was one of the founding members of the Society of California Pioneers. He was also the son of Rear Admiral Charles Boarman and uncle of fellow pioneer doctor Charles B. Harris.
Biography.
Charles Boarman was born in Martinsburg, Virginia on October 28, 1828. He was one of ten children born to Mary Ann "Nancy" Abell and Rear Admiral Charles Boarman (1795–1879), then a lieutenant in the United States Navy. The young Boarman earned a medical degree at Georgetown University and, shortly after graduating from St. Mary's School, he headed for California at age 23. Boarman settled in Sacramento County in 1851 and eventually married Mary Anna Hills. His wife was a member of an old New England family; her mother, Mary Morse Hills, was a descendant of Anthony Morse who arrived from Wiltshire, England, in 1635 to help found Newbury, Massachusetts. Mary Anna's cousin was Samuel Morse, the inventor of the telegraph. Charles Boarman and Mary Ann Hills had seven children together, one of whom died.
In early 1859, Boarman and his family moved to Lancha Plana, a booming mining town on the Mokelumne River, and were among the first to permanently settle in Amador County, California. In the summer of that year, he and another doctor treated at least one Native American, using squaws as nurses, after fighting broke out between settlers and Jackson Valley Indians. His wife was also commended for her actions during the emergency, when it was believed that a 300-man Tuolumne war party was about to raid Lancha Plana, being a voice of reason to calm the worried residents.
He was a charter member of the Amador Society of California Pioneers and presided over the Amador County chapter's first session in Jackson, California on September 9, 1877. Boarman spent seventeen years as the county physician until his death on November 22, 1880, while fighting a smallpox epidemic. His wife Mary Ann died in San Francisco in December 1897, and was buried in Jackson alongside her late husband and mother. Their daughter Emma, with her husband James J. Wright, occupied the family home and, as of 1928, was the last of the family still living in the region.


Beta adrenergic receptor kinase carboxyl-terminus

Beta adrenergic receptor kinase carboxyl-terminus (also βARKct) is a peptide composed of the last 194 amino acid residues of the carboxyl-terminus of beta adrenergic receptor kinase 1 (βARK1). It binds the βγ subunits of G proteins located in the plasma membrane of cells. It is currently an experimental gene therapy for the treatment of heart failure.
Heart Failure.
During heart failure, the heart is not able to pump enough blood to the rest of the body and will begin to undergo processes in order to compensate for its decreased function. These processes will attempt to increase the heart’s output; however, the heart may become overstressed and eventually dysfunctional as a result. The sympathetic nervous system increases norepinephrine release to stimulate β-adrenergic receptors (βARs) located on heart cell (cardiomyocyte) membranes to increase the heart’s rate and force of contraction. If the heart is already stressed or damaged, this will cause the heart to work above its capacity. Continuous stimulation of the βARs leads to the activation of βARK1 which phosphorylates βARs to decrease their response to norepinephrine and other catecholamines. βARs are downregulated as a result, decreasing the control over the heart’s rate and force of contraction. A cycle begins as more norepinephrine is produced in an attempt to stimulate the heart to contract.
Functions.
The βARKct peptide acts by binding to Gβγ proteins, competing with βARK1 for the same binding site. βARK1 requires binding to Gβγ protein-coupled receptors to be activated. By inhibiting βARK1, βARs will be upregulated back to a normal range. With βAR function restored in a failing heart, the force of contraction increases and the levels of catecholamines and growth factors return to normal.
Additionally, when βARs are activated, βARKct will bind Gβγ proteins to prevent their interaction with and inhibition of the L-type calcium channels (LCC) present on cardiomyocyte plasma membranes. This increases the flow of calcium ions through the LCCs during depolarization of the cardiomyocyte, increasing calcium levels for contraction to occur. This mechanism has been demonstrated under "in vitro" conditions and may work with the inhibition of βARK1 to restore βAR function.
Gene Therapy.
The main approach to treatment using βARKct is to insert the gene coding for it into a virus and then infecting cardiomyocytes with it. The virus, containing the βARKct gene, may be injected directly into the left coronary artery or the left ventricular walls following surgical opening of the thorax. A less invasive method for transfer is by using a catheter to inject the virus directly into the left coronary artery without opening the chest cavity.
Experimental Animal Models.
The use of βARKct gene therapy in humans is still under investigation with no trials currently being carried out. The effectiveness of this therapy has been shown in small animal models including mice, rats, and rabbits. Larger animal models, such as pig hearts, more resemble the human heart and have also demonstrated the benefits of this therapy and its potential use in humans.


Dyadobacter crusticola

Dyadobacter crusticola is a Gram-negative, psychrotolerant, aerobic and non-motile bacterium from the genus of Dyadobacter which has been isolated from biological soil crusts from the Colorado Plateau in the United States.


Metiapine

Metiapine is a typical antipsychotic medication of the dibenzothiazepine group. There is scarce research on the safety and efficacy of metiapine in humans, though limited human trials exist.
Medical uses.
Metiapine has been investigated for the treatment of schizophrenia.
Side effects.
Like other typical antipsychotics, it has a high rate of extrapyramidal side effects.
Pharmacology.
Metiapine has strong antidopaminergic effects and is classified as a typical (i.e., first-generation) antipsychotic.
Chemistry.
Metiapine is a dibenzothiazepine derivative. Like clothiapine, metiapine has a sulfur atom replacing the nitrogen atom found in dibenzapine derivative antipsychotics like clozapine.
Synthesis.
Metiapine can be synthesized through the following mechanism:
History.
Metiapine was first discovered in the 1970s by Marion Merrell Dow (now a part of Sanofi).
Research.
A 2017 Cochrane Review provided guidance for a double-blind, randomized controlled trial of metiapine versus chlorpromazine for the treatment of schizophrenia, though the authors acknowledged that it is unlikely that any future trials will investigate the use of metiapine in humans. The available evidence for the use of metiapine is very limited.


Desulfofaba gelida

Desulfofaba gelida is a Gram-negative, sulfate-reducing and psychrophilic bacterium from the genus of Desulfofaba which has been isolated from marine mud from Hornsund in Norway.


Claude Klee

Claude Klee (1932 – 4 April 2017) was a French biochemist.
Biography.
Claude B. Klee attended the University of Marseille until she graduated with her medical degree in 1959. She moved to the United States to work at the National Institute of Mental Health and also spent some time in Basel. In 1961 Klee began to work at the National Institutes of Health with Herbert Tabor, Louis Sokoloff and Maxine Singer. By 1966 Klee had a laboratory at the National Institute of Arthritis and Metabolic Diseases. In 1974 she started what was to become her iconic work at the National Cancer Institute's Biochemistry Laboratory which led to the 1991 Presidential Rank Awards. Klee was elected to the National Academy of Medicine in 1992. She also won the FASEB Excellence in Science Award. From 1995 Klee was a member of the American Academy of Arts and Sciences. Klee was also awarded the Women in Science and Engineering (WISE) Lifetime Achievement Award. She died in 2017 in Maryland, US.
Klee met her husband, Werner Klee, while working at Basel. The couple had two children.


Beta-2 adrenergic antagonist

A Beta-2 adrenergic antagonist (β2-adrenoceptor antagonist) is an adrenergic antagonist which blocks the beta-2 adrenergic receptors of cells, with either high specificity (an antagonist which is selective for β2 adrenoceptors) like Butaxamine and ICI-118,551, or non-specifically (an antagonist for β2 and for β1 or β3 adrenoceptors) like the non-selective betablocker Propranolol.


Recombinase

Recombinases are genetic recombination enzymes.
Site specific recombinases.
DNA recombinases are widely used in multicellular organisms to manipulate the structure of genomes, and to control gene expression. These enzymes, derived from bacteria (bacteriophages) and fungi, catalyze directionally sensitive DNA exchange reactions between short (30–40 nucleotides) target site sequences that are specific to each recombinase. These reactions enable four basic functional modules: excision/insertion, inversion, translocation and cassette exchange, which have been used individually or combined in a wide range of configurations to control gene expression.
Types include:
Homologous recombination.
Recombinases have a central role in homologous recombination in a wide range of organisms. Such recombinases have been described in archaea, bacteria, eukaryotes and viruses.
Archaea.
The archaeon "Sulfolobus solfataricus" RadA recombinase catalyzes DNA pairing and strand exchange, central steps in recombinational repair. The RadA recombinase has greater similarity to the eukaryotic Rad51 recombinase than to the bacterial RecA recombinase.
Bacteria.
RecA recombinase appears to be universally present in bacteria. RecA has multiple functions, all related to DNA repair. RecA has a central role in the repair of replication forks stalled by DNA damage and in the bacterial sexual process of natural genetic transformation.
Eukaryotes.
Eukaryotic Rad51 and its related family members are homologous to the archaeal RadA and bacterial RecA recombinases. Rad51 is highly conserved from yeast to humans. It has a key function in the recombinational repair of DNA damages, particularly double-strand damages such as double-strand breaks. In humans, over- or under-expression of Rad51 occurs in a wide variety of cancers.
During meiosis Rad51 interacts with another recombinase, Dmc1, to form a presynaptic filament that is an intermediate in homologous recombination. Dmc1 function appears to be limited to meiotic recombination. Like Rad51, Dmc1 is homologous to bacterial RecA.
Viruses.
Some DNA viruses encode a recombinase that facilitates homologous recombination. A well-studied example is the UvsX recombinase encoded by bacteriophage T4. UvsX is homologous to bacterial RecA. UvsX, like RecA, can facilitate the assimilation of linear single-stranded DNA into an homologous DNA duplex to produce a D-loop.


Mycena stylobates

Mycena stylobates, commonly known as the bulbous bonnet, is a species of inedible mushroom in the family Mycenaceae. Found in North America and Europe, it produces small whitish to gray fruit bodies with bell-shaped caps that are up to in diameter. The distinguishing characteristic of the mushroom is the fragile stipe, which is seated on a flat disk marked with distinct grooves, and fringed with a row of bristles. The mushrooms grow in small troops on leaves and other debris of deciduous and coniferous trees. The mushroom's spores are white in deposit, smooth, and ellipsoid-shaped with dimensions of 6–10 by 3.5–4.5 μm. In the development of the fruit body, the preliminary stipe and cap structures appear at the same time within the primordium, and hyphae originating from the stipe form a cover over the developing structures. The mycelia of the mushroom is believed to have bioluminescent properties.
Taxonomy.
The species was first named "Agaricus stylobates" by Christian Hendrik Persoon in 1801, and sanctioned under this name by Elias Magnus Fries. It was later transferred to the genus "Mycena" in 1871 by Paul Kummer when he raised many of Fries' "tribes" to the rank of genus. The species has also been placed in the genera "Basidopus" by Franklin Sumner Earle in 1909, and "Pseudomycena" by Karel Cejp in 1930; both of those genera have since been subsumed into "Mycena".
The Greek word "stylobates" means "column foundation or base". The mushroom is commonly known as the "bulbous bonnet". British mycologist Mordecai Cubitt Cooke called it the "discoid Mycena" in his 1871 "Handbook of British Fungi".
Description.
The cap of "M. stylobates" is in diameter, and depending on its age may range in shape from obtusely conic to convex to bell-shaped to flattened. The structure of the cap margin also depends on the age of the mushroom, progressing from straight or curved inward slightly, to margin flaring or curved backward. The cap surface is smooth, although if viewed with a magnifying glass, minute spines can be seen. As it ages, the surface becomes smooth, moist and somewhat glistening, and it shows grooves corresponding to the position of the gills underneath the cap. The cap color is evenly pale watery gray. The flesh is thin, pallid, and has no distinguishable odor or taste.
The gills appear closely spaced in unexpanded caps, but usually more distant in old individuals. Between 8 and 16 gills extend from the margin to the stipe; there are additionally one or two tiers of small gills ("lamellulae") that do not reach fully from the margin to the stipe. The gills are narrow but become ventricose (swelling in the middle) and sometimes very broad in age, and are attached by a line or are very narrowly adnate. Sometimes the gills split away from the stipe while remaining attached to each other; in this way they form a collar around the stipe. Gills are pale gray but soon become whitish, with even edges. The stipe is long, 0.5–1 mm thick, and, above the level of the flat circular disc at the base, is equal in width throughout. The stipe is covered with fine white scattered fibrils, or is delicately pruinose (as if covered with a fine white powder), but it later becomes smooth. Its color is bluish-gray when fresh but soon it fades to gray. The basal disc is grooved (from gill impressions) and pruinose or covered with fine minute hairs, but soon becomes smooth. The insubstantial fruit bodies are considered inedible.
Microscopic characteristics.
The spores are 6–10 by 3.5–4.5 μm, narrowly ellipsoid, and faintly amyloid. The basidia (spore-bearing cells) are four-spored, rarely two-spored. The pleurocystidia (cystidia on the gill face) are not differentiated. The cheilocystidium (cystidia on the gill edge) are abundant and variable in structure, usually club-shaped with between two and five thick obtuse projections that arise from near the apex, sometimes more or less covered with numerous protuberances over the enlarged portion and the neck more or less contorted. They measure 26–38 by 8–13 μm, and are hyaline. The gill flesh is made of greatly enlarged cells, and stains pale vinaceous (red wine color) in iodine. The flesh of the cap has a pellicle which usually gelatinizes in potassium hydroxide or water mounts prepared for microscopy. The surface hyphae are covered with short rodlike projections. Sometimes some of the hyphae become aggregated into peglike structures that project from the surface, and cause the appearance of scattered coarse spines on the cap when viewed under a 10X magnifying lens. The tissue beneath the pellicle is made entirely of greatly enlarged cells, which appear pale vinaceous in iodine stain.
The mycelia of "M. stylobates", when grown in pure culture, is bioluminescent, a phenomenon first reported in 1931. The fruit bodies are not known to be bioluminescent.
Similar species.
There are several species of "Mycena" that have a basal disc similar to "M. stylobates". "Mycena mucor" is usually smaller than "M. stylobates", and grows on fallen, decaying leaves of oak. It has different cheilocystidia, with very slender excrescences. Also, the margin of the basal disc is not ciliate like "M. stylobates". "M. bulbosa", a species that grows on woody stalks in wet habitats, has nonamyloid spores, and gill edges that contain a tough-elastic, gelatinous thread. "M. pseudoseta", described as a new species from Thailand in 2003 forms smaller fruit bodies with differently shaped cheilocystidia and cap hyphae.
Fruit body development.
The ontogeny, or development, of "Mycena stylobates" fruit bodies has been investigated in detail using light microscopy and scanning electron microscopy. According to Volker Walther and colleagues, the development can be divided into two phases: in the first, the primordium is established that contains all the structures of the mature fruit body; in the second stage, the primordial stipe elongates rapidly, and the newly exposed hymenium immediately begins spore production. The first detected stage of fruit body formation was an irregularly arranged hyphal structure within the colonized substrate. After rupturing the surface of the substrate and establishing itself there, the structure develops a layer of wrapping hyphae that covers the entire primordium. The structures of the stipe and the cap develop simultaneously. The developing stipe, cap, and basal disc together form a secondary ring-like cavity, in which the gills develop. Gill development initiates with a number of small alveolae on the lower side of the cap, which are covered with a hymenophoral palisade (a group of tightly packed, roughly parallel cells). The margins of these alveolae form the primary gills. The hymenophoral palisade spreads from the developing alveolae to the gill edge; the edge of the primary gills is forked in the early stages of its development. The secondary gills (lamellulae) are formed by the ridges folding down from the lower side of the cap. In contrast to the primary gills, they are covered with hymenophoral palisade from the beginning. Spore production begins immediately after the stipe elongates.
Habitat and distribution.
The fruit bodies of "Mycena stylobates" grow scattered or in groups on oak leaves or coniferous needles, in the spring and summer or early autumn. It is common during warm, wet seasons. "Mycena" specialist Alexander H. Smith has collected it in Tennessee, Michigan, Idaho, and Washington in the United States, and in Nova Scotia and Ontario in Canada. It is also found in Europe, including Britain, Denmark, Germany, Norway, Poland, Romania, Scotland, Serbia, Sweden, and Turkey. Although it has been reported several times from Australia, mycologist Cheryl Grgurinovic concluded in a 2003 publication that the records "are best regarded as erroneous".


Molecular and Cellular Biochemistry

Molecular and Cellular Biochemistry is a peer-reviewed scientific journal covering research in cellular biology and biochemistry. It was a successor to the journal "Enzymologia" and was established in 1973 to make "it possible to extend the potentialities of the periodical".
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2011 impact factor of 2.057.


Grylloblattidae

Grylloblattidae, the icebugs, or ice crawlers, is a family of extremophile (psychrophile) and wingless insects that live in the cold on top of mountains and the edges of glaciers. They belong, along with Mantophasmatidae (rock crawlers), to the order Notoptera. Grylloblattids are tiny, most being less than 3 cm long, wingless insects with a head resembling that of a cockroach, with long antennae and having elongated cerci arising from the tip of their abdomen. They cannot tolerate warmth (most species will die at 10 °C) and many species have small distribution ranges.
Overview.
Grylloblattids, ice crawlers or icebugs puzzled the scientists who discovered them in 1914, E.M. Walker and T.B. Kurata; the first species named was "Grylloblatta campodeiformis", which means "cricket-cockroach shaped like a "Campodea"" (a kind of two-pronged bristletail). Most are nocturnal and appear to feed on detritus. They have long antennae (23–45 segments) and long cerci (5–8 segments), but no wings. Their eyes are either missing or reduced and they have no ocelli (simple eyes). Their closest living relatives are the recently discovered Mantophasmatodea. Most species are less than 3 cm long, the largest being "Namkungia magnus".
The family has its own suborder, Grylloblattodea (formerly its own order). It contains 5 genera and about 34 extant species.
Most species have restricted distributions and small populations and with increased warming their habitats are threatened, making them endangered. In North America some species like "Grylloblatta barberi" and "G. oregonensis" are known from single sites.
Habitat and distribution.
Grylloblattodea are nocturnal extremophiles typically found in leaf litter and under stones in extremely cold environments, usually at higher elevations. They are known to inhabit cold temperate forests to glaciers and the edges of ice sheets. Their optimal living temperature is between 1-4 °C (33.8-39.2 °F). They can be killed at colder temperatures due to ice formation in the body, so when the temperature drops below their optimal range they survive by living under snow pack near the soil. They have a very narrow range of temperatures that they prefer and cannot withstand high temperatures; many species are killed when the temperature rises about 5°C above their optimal. They move in response to the seasons so as to maintain an optimal temperature in their foraging habitat.
Grylloblattidae are patchily distributed on glaciers in North America, China, Siberia, Korea and Japan. They are predicted to occur in several other mountain chains in Asia including parts of the Himalayas.
Diet.
They are omnivorous, but feed primarily on dead arthropods and carrion. When arthropod carcasses are scarce, their diet relies heavily on plant material. The fossil species "Plesioblattogryllus magnificus" from the Middle Jurassic had strong mandibles and is thought to have been a predator.


Nicotine dehydrogenase

In enzymology, a nicotine dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are (S)-nicotine, acceptor, and H2O, whereas its two products are (S)-6-hydroxynicotine and reduced acceptor.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with other acceptors. The systematic name of this enzyme class is nicotine:acceptor 6-oxidoreductase (hydroxylating). Other names in common use include nicotine oxidase, D-nicotine oxidase, nicotine:(acceptor) 6-oxidoreductase (hydroxylating), and L-nicotine oxidase. It has 2 cofactors: metal, and FMN.


Beta-peptide

β-peptides are peptides derived from β-amino acids. The parent β-amino acids is H2NCH2CH2CO2H but most examples feature substituents in place of one or more C-H bonds. The only common naturally occurring β amino acid is β-alanine. β-peptides in general do not appear in nature. β-peptide-based antibiotics are being explored as ways of evading antibiotic resistance. Early studies in this field were published in 1996 by the group of Dieter Seebach and that of Samuel Gellman.
Synthesis.
Two main types of β-peptides exist: those with the organic residue (R) next to the amine are called β3-peptides and those with position next to the carbonyl group are called β2-peptides.
β-Amino acids have been prepared by many routes. notably those based on the Arndt-Eistert synthesis.
Secondary structure.
Because their backbones are longer than those of normal peptides, β-peptides form disparate secondary structures. The alkyl substituents at both the α and β positions in a β amino acid favor a gauche conformation about the bond between the α-carbon and β-carbon. This also affects the thermodynamic stability of the structure.
Many types of helix structures consisting of β-peptides have been reported. These conformation types are distinguished by the number of atoms in the hydrogen-bonded ring that is formed in solution; 8-helix, 10-helix, 12-helix, 14-helix, and 10/12-helix have been reported. Generally speaking, β-peptides form a more stable helix than α-peptides.
Clinical potential.
β-peptides are stable against proteolytic degradation in vitro and in vivo, an potential advantage over natural peptides. β-Peptides have been used to mimic natural peptide-based antibiotics such as magainins, which are highly potent but difficult to use as drugs because they are degraded by proteolytic enzymes.
List.
8 beta forms exist: alanine, leucine, lysine, arginine, glutamate, glutamine, phenylalanine, tyrosine forms. Aspartic acid is regarded as both beta and alpha forms, although the beta form is found in microcystins.


Ryan Bethencourt

Ryan Bethencourt (March 18, 1979) is an American scientist, entrepreneur, and biohacker best known for his work as co-founder and CEO of Wild Earth, Partner at Babel Ventures and cofounder and former Program Director at IndieBio, a biology accelerator and early stage seed fund. Bethencourt was head of life sciences at the XPRIZE foundation, a co-founder and CEO of Berkeley Biolabs, a biotech accelerator, and Halpin Neurosciences, an ALS therapeutics-focused biotech company. Bethencourt co-founded Counter Culture Labs, a citizen science nonprofit, and Sudo Room, a hacker space based in downtown Oakland, California.
Bethencourt is a vegan and has worked on the development of several sustainable and cruelty-free products.
Early life.
Bethencourt has worked over the last decade in the biopharmaceutical industry to partner on and develop novel drugs from first IND submission to FDA approval with many major biopharmas including Pfizer, AZ, J&J, Sanofi, Takeda, Amgen, Genentech, and other companies in the U.S., E.U., and Japan. He has also served as COO at Genescient Pharmaceuticals, a longevity focused biotech startup and CEO of Halpin Neurosciences, an ALS focused startup. Bethencourt’s work has been featured in Wired, TechCrunch, Forbes, the San Francisco Business Times, and other publications. He regularly speaks on biotech innovation and writes for Biocoder, an O’Reilly Media publication. He's also an author of Forbes, Techonomy and Huffington Post.
Since Bethencourt co-founded IndieBio in 2014, he and his team have funded 68 biotech startups, including companies building the post-animal bioeconomy: Clara Foods, Memphis Meats, Gelzen, New Wave, and Pembient. He's also an advisor of The Good Food Institute.
Education.
Bethencourt has a BSc degree in Biological Sciences (Molecular Genetics) from Warwick University in the United Kingdom. He also has a Masters in Bioscience Enterprise (MBE) from Cambridge University (2002 – 2003). This masters course was the first of its kind in the UK (launched in 2002) and it was a fusion of the MBA/Biotech courses and launched in partnership with Harvard and MIT. He has also been a Doctor of Philosophy (PhD) Candidate at the Center for Regenerative Medicine at the University of Edinburgh in 2003 working on stem cell differentiation. .
Companies Invested/Co-Founded.
• NERD Skincare
• Gelzen
• V-Sense Medical
• Memphis Meats
• Vali Nanomedical
• INDEE
• Truust
• Koniku
• Girihlet
• MYi
• Circularis
• New Wave Foods
• Amino BioLabs
• Gene and Cell Technologies
Advised:
• Berkeley ultrasound
Co Founded:
• Sudo Room
• Counter Culture Labs
• Berkeley Biolabs
• LAbLaunch
• IndieBIo
• Wild Earth
Global Forum 2015.
Bethencourt joined the Global Forum 2015 as one of the speakers. The Global Forum on Research and Innovation for Health 2015, aimed to identify solutions to the world’s unmet health needs through research and innovation. The said forum was held on August 24–27, 2015 at Philippines International Convention Center(PICC), Metro Manila, Philippines. Bethencourt spoke about the topic of "Increasing public expenditure on research and innovation in emerging economies" and "Increasing investments for innovative andpractical solutions to priority healthcare".
Pioneers Asia 2016.
Bethencourt was a part of Pioneers Asia 2016 on Mar 23, 2016 at Tokyo, Japan . Pioneers facilitates profound business relationships between tech innovators. The event was for tech entrepreneurs, investors, top executives, thought-leaders, and international media from Europe to Asia, Middle East, and beyond. Bethencourt spoke about BIOTECH FOR THE WORLD OF THE FUTURE. He also moderated the life sciences and agriculture topic on the said event.


Phenylacetyl-CoA dehydrogenase

In enzymology, a phenylacetyl-CoA dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are phenylacetyl-CoA, H2O, and quinone, whereas its two products are phenylglyoxylyl-CoA and quinol.
This enzyme belongs to the family of oxidoreductases, specifically those acting on CH or CH2 groups with a quinone or similar compound as acceptor. The systematic name of this enzyme class is phenylacetyl-CoA:quinone oxidoreductase. This enzyme is also called phenylacetyl-CoA:acceptor oxidoreductase.


Genetics Institute

Genetics Institute, Inc. was a biotechnology research and development company founded by Thomas Maniatis and Mark Ptashne, two Harvard molecular biologists, in 1980 in Massachusetts. Originally operating out of Ptashne's house in Boston, the company found more spacious quarters first in Boston and then Cambridge before expanding further. Gabriel Schmergel joined soon afterwards as CEO.
Many leading scientists joined G.I. from academia and it proved to be a fertile source of patents for some time.
Historical background.
One of the two largest national clusters of biotechnology in the U.S. (the other being the San Francisco Bay area), the greater Boston area has been the birthplace of many innovative corporations and non-profit research centers.
Beginning in the late 1970s and 1980s, this biotech trend saw three early large for-profit corporations: Biogen (now Biogen Idec), Genzyme, and Genetics Institute. MIT's Whitehead Institute was one of the seminal non-profit research centers in this field locally, among many others. Aside from MIT, Harvard, Boston University and several teaching hospitals including Massachusetts General Hospital and Brigham and Women's were important contributors to the local field's development.
Products.
G.I.'s Products (or potential candidates for products) included forms of M-CSF, interleukin-3, interleukin-11 (Neumega), bone morphogenetic protein 2,recombinant human Factor IX, and recombinant human Factor VIII (Recombinate); as well as tissue plasminogen activator and erythropoetin that both involved costly, complex lawsuits over patent infringement with competitors.
Toward the end of its independent existence, G.I. created a program to share "a library of several thousand genes and their related proteins that could be scanned for potential new drugs."
This program was based on a G.I. technology that allowed it to identify proteins secreted by cells and therefore more likely to be therapeutic in the body.
Dissolution.
Wyeth (American Home Products at the time) acquired a majority interest in GI in 1992 and the remaining interest at the end of 1996. The company became part of Wyeth's Research division.


GenScript Biotech

GenScript Biotech Corporation (Stock Code: 1548.HK) is a global biotechnology group. Built upon leading gene synthesis technology, GenScript consists of four major groups:
GenScript was founded in New Jersey, United States in 2002, by Dr. Fangliang (Frank) Zhang, and listed on the Hong Kong Stock Exchange in 2015. Currently, GenScript is under the leadership of rotating CEO, Dr. Zhenyu Liu., GenScript's business operations span over 100 countries and regions worldwide with legal entities located in the US, China, Hong Kong, Japan, Singapore, the Netherlands, and Ireland. GenScript provides products and services to over 100,000 customers.,
As of June 30, 2020, GenScript had more than 3,900 employees globally, over 36% of whom hold master's and/or Ph.D. degrees. In addition, GenScript owns a number of intellectual property rights and trade secrets, including over 140 patents and over 450 pending patent applications.
GenScript is driven by the corporate mission of “making people and nature healthier through biotechnology”. As of June 30, 2020, GenScript's products or services have been cited by 51,000 peer-reviewed journal articles worldwide.
In September 2020 it was reported Chairman and founder of Genscript Fangliang Zhang was arrested and put under “residential surveillance,” due to alleged breaches of China's tight rules on the exports of human genetic resources. Anti-smuggling officials also raided their offices in Nanjing and Shenjiang, with Genscript stating they would assist authorities with the investigation.
GenScript Biotech’s business segments.
GenScript Life Science Group.
GenScript Life Science Group is GenScript's original business unit. Based on its independent and leading gene synthesis technology, the GenScript Life Science business has grown to become the world's largest gene synthesis provider with a market share of approximately 30%. The Group now has nearly 2,000 employees worldwide, covering China, North America, Europe, and Asia Pacific.
For over 20 years, GenScript Life Science Group has supported global scientists achieve research results and promoted the rapid advancement of life sciences over the past 20 years. In 2011, GenScript was selected as the sole business entity to participate in the Synthetic Yeast Genome Sc2.0 Project. As of December 31, 2019, GenScript Life Science Group has delivered more than 2 million genes at a 99.95% success rate and over 98.5% on-time delivery rate, as well as 100% sequence accuracy rate. The delivered products have been cited in more than 42,200 scientific papers. Throughout the past decade, GenScript was awarded the CRO Leadership Award by Life Science Leader Magazine several times in the categories of quality, productivity, innovation, and reliability.
Supported by next-generation DNA Synthesis and HD Protein Expression technologies, GenScript's Life Science CRO platform continues to expand its business strategy in five application areas - retail reagents, industrial solutions, therapeutic materials, supportive diagnostic materials and research instruments and consumables - providing global scientists with simple, fast and precise scientific research solutions and harnessing the power of synthetic biology to speed up pharmaceutical R&D., ,
GenScript ProBio – Bio-pharmaceutical CDMO.
GenScript ProBio is the bio-pharmaceutical CDMO segment, providing end-to-end service from drug discovery to commercialization with proactive strategies, professional solutions and efficient processes to accelerate drug development.
GenScript ProBio provides solutions for antibody drug development including antibody drug discovery (hybridoma, antibody library, fully human transgenic mice, bispecific antibodies technologies, single B cell screening technology), antibody engineering (antibody humanization, affinity maturation, Fc Engineering), and antibody characterization (analytics and bioassays). For biologics development service, GenScript ProBio has built a regulatory-compliant platform, from stable cell line development to clinical manufacturing services, providing high quality materials for IND and clinical trials to accelerate the drug development process. GenScript ProBio's total gene and cell therapy solution covers CMC of plasmid and virus for IND filing as well as clinical manufacturing and commercial manufacturing.
GenScript ProBio follows the corporate mission of “Innovation through Collaboration”, to shorten the timeline for the development of biological drugs from discovery to commercialization, significantly lowering R&D costs.
Legend Biotech – Cell Therapy.
A a subsidiary of GenScript Biotech Corporation, Legend Biotech (NASDAQ: LEGN) is a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncological and other indications. Legend Biotech's team includes over 650 employees across the United States, China and Europe. Along with differentiated technology, development, and manufacturing strategies and expertise, Legend Biotech is engaged in the discovery, development, and manufacturing of cell therapies for patients in need.
Legend Biotech has established a strategic collaboration with Janssen Biotech to develop and commercialize the lead product candidate, LCAR-B38M/JNJ-4528, an investigational BCMA-targeted CAR-T cell therapy for patients living with relapsed or refractory multiple myeloma. This candidate is currently being studied in registrational clinical trials.
Bestzyme – Industrial Synthesis Product.
Nanjing Bestzyme Bioengineering Co., Ltd. (Bestzyme), is one of GenScript's subsidiaries integrating the development of enzyme preparations and the development, production, and sales of enzyme catalysis technology for active product ingredients (APIs). Dedicated to biosynthesis technology, Nanjing Bestzyme has established a fully integrated end-to-end system incorporating development, production and marketing - from enzyme screening, genetic engineering, protein engineering transformation, fermentation process optimization, application research to technical support and follow-up services.
Established in 2013, Nanjing Bestzyme drives innovation through "independent R&D, core technology advancement, and complete ownership of intellectual property rights." Nanjing Bestzyme has independently developed multiple industrial, food and medical enzyme products such as pullulanase, phytase and glucose oxidase, in addition to a number of product lines with industry-leading performance.
History and Achievements.
2002, GenScript was founded in New Jersey, USA.
2004, GenScript established research and production center in Nanjing, China.
2011, GenScript opened a new Nanjing research and production facility and established a subsidiary in Japan.
2013, GenScript launched Bestzyme (biotech industrial synthetic biology) product segment.
2014, GenScript launched Legend Biotech cell therapy segment.
2015, GenScript Biotech Corporation was listed in HKEK (Stock code:1548).
2017, the China Food and Drug Administration (CFDA) accepted the IND application by Legend. Collaboration on BCMA program was established between Legend and Janssen.
2018, Legend's BCMA program received IND clearance in the United States and China. GenScript's Biologics CDMO segment was established.
2019, GenScript launched its new Biologics GMP CDMO R&D center and established its European and Asia-Pacific division. Legend's BCMA program received Orphan drug designation (FDA) & PRIME designation (EMA), US phase 1b data at ASH 2019: ORR 100%.
2020, GenScript Life Science CRO achieved consecutive growth. GenScript and Duke-NUS Medical School co-developed cPass sVNT kit, first in the world SARS-CoV-2 serology test to detect neutralizing antibodies., , Legend Biotech was listed on NASDAQ (stock code: LEGN), the biggest IPO for a biotech company 2020.,


Procinolol

Procinolol is a beta adrenergic receptor antagonist, a group of pharmaceutical drugs that lower heart rhythm and blood pressure.
It is not known to be marketed anywhere in the world in 2021.