Mary Foster (biochemist)

Mary Louise Foster (April 20, 1865June 21, 1960) was an American biochemist, research chemist and educator.
Education.
Mary Louise Foster was born on April 20, 1865 in Melrose, Massachusetts. Between the years of 1878-1883, she attended the Girls' Latin School in Boston, MA, and later went on to study Classics at Smith College from 1888 to 1891. After her graduation, Foster taught Chemistry and Physics at West Roxbury High School while enrolled at the Massachusetts Institute of Technology in Boston (1893-1895). In 1912, she received her master's degree from Smith, and two years later earned her PhD from the University of Chicago. She spent the summer of 1917 at the Rockefeller Institute for Medical Research.
Career.
In 1898, Foster found work teaching chemistry at Lynn High and Classical School. The next year, she became an assistant researcher in the Lab of Physiology and Chemistry in New York, where she stayed until 1901. In 1903, Foster worked as a research chemist in the department of pharmacology at Columbia University, where she stayed on until 1907. Concurrent with her research, she was also a professor in the chemistry department at the Woman's Medical College of New York (1904-1905). After working at Columbia University, Foster was appointed as an instructor and later associate professor at Smith College, where she played a major role in introducing the field of biochemistry to the curriculum. She offered the first biochemistry course during 1916-17, and with the exception of the semesters she was on sabbatical leave, taught this and other biochemistry courses until her retirement in 1933.
In 1920, she was offered the position of Director at the International Institute for Girls in Spain, located in Madrid. She stayed there for two years, before returning to Smith as the Chairman of the Committee on Interdepartmental Majors, a position she held until 1927. In 1928, she was appointed a member of the Special Honors Committee. From 1930 to 1932, Foster returned to lab she helped to establish in Spain to work as the lab organizer. Following her second brief tenure at the Institute, she then relocated to Santiago College in Chile to work as the Director of New Laboratories in Chemistry and Physics. It was there that she did the majority of her most notable research, publishing numerous times and delivering several lectures in her field.


Jin Zhang (biochemist)

Jin Zhang (; born February 29, 1972) is a Chinese-American biochemist. She is a professor of pharmacology, chemistry and biochemistry, and biomedical engineering at the University of California, San Diego.
Early life and education.
Zhang was born in Beijing, China. She received her B.S. in chemistry from Tsinghua University in Beijing in 1995. She completed her Ph.D. with David G. Lynn at the University of Chicago in 2000, and conducted postdoctoral research with Roger Y. Tsien and Susan S. Taylor at the University of California, San Diego.
Academic career.
Following her postdoc at UCSD, Zhang joined the faculty in the Department of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine in 2003. At Johns Hopkins, she was a member of the Sidney Kimmel Comprehensive Cancer Center. In 2013, she was promoted to full professor in the departments of Pharmacology and Molecular Sciences, Solomon H. Snyder Department of Neuroscience and Department of Oncology, and Department of Chemical and Biomolecular Engineering.
In 2015, Zhang relocated her lab to UCSD, where she is a professor in the departments of Pharmacology, Bioengineering, and Chemistry and Biochemistry. She is a member of the Moores Cancer Center. Zhang is also director and cofounder of the Bio-Optical Probe Advancement Center at UCSD.
Zhang is an editorial board member for Cell Chemical Biology.
Research.
The Zhang group is interested in developing genetically encoded fluorescent protein-based biosensors for kinases, similar to those developed for calcium imaging. Genetically encoded biosensors utilize a kinase-specific substrate fused to fluorescent proteins and a phosphoamino acid binding domain, which change FRET ratio or fluorescence intensity based on kinase activity. Zhang and her lab have used this method to study several kinases, including protein kinase A, protein kinase C, and mechanistic target of rapamycin, among others. The Zhang group has also worked on super-resolution imaging techniques, including photochromic stochastic optical fluctuation imaging (pcSOFI), a variant of super-resolution optical fluctuation imaging, and fluorescence fluctuation increase by contact imaging (FLINC), which has been used to generate super-resolution kinase biosensors
Zhang, along with the help from Johns Hopkins Laboratories, is also credited for the creation of a new technique referred to as CAESAR. This technique was designed to experimentally identify substrates for unique kinases. It results in high-quality KSRs.
Honors and awards.
Zhang has received many honors and awards including:


SB-269970

SB-269970 is a drug and research chemical developed by GlaxoSmithKline used in scientific studies. It is believed to act as a selective 5-HT7 receptor antagonist (EC50 = 1.25 nM) (or possibly inverse agonist). A subsequent study in guinea pig at 10 uM showed that it also blocks the α2-adrenergic receptor activity. The significant difference in test concentrations, however, confirms the selectivity of SB-269970 for the 5-HT7 receptor.
SB-269970 is used to study the 5-HT7 receptors which are thought to be involved in the function of several areas of the brain such as the hippocampus and thalamus, and regulation of dopamine release in the ventral tegmental area. Possible therapeutic uses for SB-269970 and other 5-HT7 antagonists include the treatment of anxiety and depression, and nootropic effects have also been noted in animal studies.


Nymphon

Nymphon is a genus of sea spiders in the family Nymphonidae.
This genus may contain bioluminescent species.


DNase-Seq

DNase-seq (DNase I hypersensitive sites sequencing) is a method in molecular biology used to identify the location of regulatory regions, based on the genome-wide sequencing of regions sensitive to cleavage by DNase I. FAIRE-Seq is a successor of DNase-seq for the genome-wide identification of accessible DNA regions in the genome. Both the protocols for identifying open chromatin regions have biases depending on underlying nucleosome structure. For example, FAIRE-seq provides higher tag counts at non-promoter regions. On the other hand, DNase-seq signal is higher at promoter regions, and DNase-seq has been shown to have better sensitivity than FAIRE-seq even at non-promoter regions.
DNase-seq Footprinting.
DNase-seq requires some downstream bioinformatics analyses in order to provide genome-wide DNA footprints. The computational tools proposed can be categorized in two classes: segmentation-based and site-centric approaches. Segmentation-based methods are based on the application of Hidden Markov models or sliding window methods to segment the genome into open/closed chromatin region. Examples of such methods are: HINT, Boyle method and Neph method. Site-centric methods, on the other hand, find footprints given the open chromatin profile around motif-predicted binding sites, i.e., regulatory regions predicted using DNA-protein sequence information (encoded in structures such as Position weight matrix). Examples of these methods are CENTIPEDE and Cuellar-Partida method.


Sergeant Bill

Sergeant Bill was a Canadian goat from Saskatchewan who served as the mascot of the 5th Infantry Battalion of the Canadian Expeditionary Force during the First World War.
Bill was able to hear and warn soldiers of incoming shell explosions, pushing 3 soldiers into a trench within seconds of an incoming shell. In another instance, he cornered 3 enemy guardmen. He also assisted in guarding prisoners. Bill survived being wounded and gassed on multiple occasions. For his actions, he was awarded the 1914 Star, the General Service Medal, and the Victory Medal.
He faced courts martial on two occasions, once for eating his battalion's personnel roll and the other time for an altercation with another sergeant. He lived the remainder of his life in Winnipeg.


Laccaria amethystina

Laccaria amethystina, commonly known as the amethyst deceiver, is a small brightly colored mushroom, that grows in deciduous and coniferous forests. The mushroom itself is edible, but can absorb arsenic from the soil. Because its bright amethyst coloration fades with age and weathering, it becomes difficult to identify, hence the common name "deceiver". This common name is shared with its close relation "Laccaria laccata" that also fades and weathers. It is found mainly in Northern temperate zones, though it is reported to occur in tropical Central and South America as well. Recently, some of the other species in the genus have been given the common name of "deceiver".
Taxonomy.
This species was first described in 1778 by well-known English botanist and apothecary William Hudson as "Agaricus amethystinus", and later put into the genus "Laccaria" by Mordecai Cubitt Cooke. The amethyst deceiver has had many binomials over a great many years, but reference to the amethyst coloration is featured in most of these. It was once placed in the genus "Collybia", as "Collybia amethystina", which was probably due in part to its tough collybioid-like stem. Its present binomial places it in the genus "Laccaria", with the specific epithet "amethystina", a pairing first used by Cooke in 1884. In 1922 it was named as a variant of "Laccaria laccata", "Laccaria laccata" var. "amethystina" (Cooke) Rea, which is now a synonym.
Description.
The cap is 1–6 cm in diameter, and is initially convex, later flattening, and often with a central depression (navel). When moist it is a deep purplish lilac, which fades upon drying out. It is sometimes slightly scurfy at the center, and has pale striations at the margin. The stem is the same colour as the cap, and has whitish fibrils at the base, which become mealy at the top. It is fibrous, hollow, fairly tough when rolled in the fingers, with dimensions of long by thick. The flesh is without a distinctive taste or smell, and is thin, with pale lilac coloration. The gills are colored as the cap, often quite distantly spaced, and are dusted by the white spores; their attachment to the stem is sinuate—having a concave indentation before attaching to the stem.
Microscopic characteristics.
The spores are spherical and hyaline, and bear pointed spines (echinulate) that are long relative to the size of the spore; they typically have dimensions of 7–10 by 7–10 µm. The basidia, the spore-bearing cells, are club-shaped and hyaline, and are 30–64.5 by 8.5–14  µm.
Distribution and habitat.
"L. amethystina" is a common species in most temperate zones of Europe, Asia, Central, South, and eastern North America. It grows solitary to scattered with a variety of deciduous and coniferous trees, with which it is mycorrhizally associated, though it most commonly occurs with trees in the Fagales. It appears in late summer to early winter, and often with beech; in Central and South America, it more commonly grows in association with oak. Research has shown that "L. amethystina" is a so-called "ammonia fungus", an ecological classification referring to those fungi that grow abundantly on soil after the addition of ammonia, or other nitrogen-containing material; the congeneric species "Laccaria bicolor" is also an ammonia fungus.
Edibility.
As with other members of the genus "Laccaria", this species is edible, though generally not considered a choice edible. While not inherently toxic, in soils that are polluted with arsenic, it can bioaccumulate a high concentration of that element.
Similar species.
There are several purplish species in North America that were formally labeled as "L. amethystina" before Gregory M. Mueller described them as distinct species in 1984. Laccaria amethysteo-occidentalis is found in western North America, where "L. amethystina" does not occur. It is a very common mushroom in its geographical range. Besides geographical difference, "L. amethysteo-occidentalis" differs from "L. amethystina" in several ways: ecologically, the former occurs only in association with conifers, while the latter occurs mainly with hardwoods of the order Fagales. The sporocarp of "L. amethysteo-occidentalis" is on average larger than that of "L. amethystina", and has a deeper purple coloration, that fades to vinaceous rather than brownish shades. The spores are also quite distinct between the two, in that the spores of "L. amethysteo-occidentalis" are not as strongly globose as those of "L. amethystina", being generally of a subglobose or even broadly ellipsoid shape, and additionally having much shorter spines than the spores of "L. amethystina".
Another species that was segregated by Mueller from "L. amethystina" is Laccaria vinaceobrunnea, a species found in the Gulf Coast region of the southern United States. "L. vinaceobrunnea" is distinguished from "L. amethystina" and "L. amethysteo-occidentalis" macroscopically by color, with the former species having a deep purple color only in very young specimens, which soon fades to a violaceous- or reddish-brown color, and eventually to dull orange-brown or buff color with age. Its spore features are intermediate between "L. amethystina" and "L. amethysteo-occidentalis", having a subglobose to broadly ellipsoid shape like "L. amethysteo-occidentalis" (rather than the strongly globose shape of "L. amethystina" spores) and long spines characteristic of "L. amethystina". The pileipellis of "L. vinaceobrunnea" is unique within "Laccaria", having a distinct palisadoderm, rather than the undifferentiated type or fasciculate trichoderm that is characteristic of other species of "Laccaria". "L. vinaceobrunnea" is also somewhat distinguished by habitat, being highly specific in association with "Quercus virginiana". "L. amethystina" is also often associated with this species, but is associated with many other tree species in the Fagales as well.
In 1988, a third species of purple "Laccaria", Laccaria gomezii, was described by Mueller as distinct from "L. amethystina". This species is associated with "Quercus" and is endemic to the cloud forests of Central America and northern South America (habitats in which "L. amethystina" also occurs). "L. gomezii" is similar to "L. vinaceobrunnea" in a number of characteristics, but the fresh sporocarp is a darker purple than either "L. vinaceobrunnea" or "L. amethystina". Its lamellae distinguish it from other members of the "L. amethystina" group, with "L. gomezii" having attached to subdecurrant, very closely spaced lamellae, in contrast to the sinuate to arcuate, narrowly attached lamellae of other species in this group. The spores of "L. gomezii" are similar to those of "L. vinaceobrunnea" and "Laccaria amethysteo-occidentalis", and it lacks the distinct pileipellis hyphae of "L. vinaceobrunnea".


Insert Therapeutics

Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., is a medical research company that uses nanobiotechnology specializing in therapeutic agents that are conjugated, to facilitate and enhance drug delivery. The small company was founded in 2000, is located in Pasadena, California, and is owned by Arrowhead Research Corporation.
The conjugates consist of a cyclodextrin-containing polymer (Cyclosert) that acts as a drug delivery system, and a linked medication, such as a chemotherapeutic drug of already proven efficacy. The size of the polymer is designed to “fit” the specific target, as vessels in a neoplasm allow for leakage of different sizes of polymers, as in healthy tissue. The leaked conjugates are concentrated in the target area. As a result, chemotherapeutic activity is locally enhanced, while general side effects are decreased.
At least one of their conjugates, IT-101, has been investigated in a clinical trial at City of Hope National Medical Center.


L-aspartate oxidase

In enzymology, a L-aspartate oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-aspartate, H2O, and O2, whereas its 3 products are oxaloacetate, NH3, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is L-aspartate:oxygen oxidoreductase (deaminating). This enzyme participates in alanine and aspartate metabolism and nicotinate and nicotinamide metabolism. It employs one cofactor, FAD.
Structural studies.
As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes , , and .


Peptoid

Peptoids, or poly-"N"-substituted glycines, are a class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, rather than to the α-carbons (as they are in amino acids).
Chemical structure and synthesis.
In peptoids the side chain is connected to the nitrogen of the peptide backbone, instead of the α-carbon as in peptides. Notably, peptoids lack the amide hydrogen which is responsible for many of the secondary structure elements in peptides and proteins. Peptoids were first invented by Reyna J. Simon, Paul Bartlett and Daniel V. Santi to mimic protein/peptide products to aid in the discovery of protease-stable small molecule drugs.
Following the sub-monomer protocol originally created by Ron Zuckermann, each residue is installed in two steps: acylation and displacement. In the acylation step a haloacetic acid, typically bromoacetic acid activated by diisopropylcarbodiimide reacts with the amine of the previous residue. In the displacement step (a classical SN2 reaction), an amine displaces the halide to form the "N"-substituted glycine residue. The submonomer approach allows the use of any commercially available or synthetically accessible amine with great potential for combinatorial chemistry.
Unique characteristics.
Like D-Peptides and β peptides, peptoids are completely resistant to proteolysis, and are therefore advantageous for therapeutic applications where proteolysis is a major issue. Since secondary structure in peptoids does not involve hydrogen bonding, it is not typically denatured by solvent, temperature, or chemical denaturants such as urea (see details below).
Notably, since the amino portion of the amino acid results from the use of any amine, thousands of commercially available amines can be used to generate unprecedented chemical diversity at each position at costs far lower than would be required for similar peptides or peptidomimetics. To date, at least 230 different amines have been used as side chains in peptoids.
Structure.
Peptoid oligomers are known to be conformationally unstable, due to the flexibility of the main-chain methylene groups and the absence of stabilizing hydrogen bond interactions along the backbone. Nevertheless, through the choice of appropriate side chains it is possible to form specific steric or electronic interactions that favour the formation of stable secondary structures like helices, especially peptoids with C-α-branched side chains are known to adopt structure analogous to polyproline I helix. Different strategies have been employed to predict and characterize peptoid secondary structure, with the ultimate goal of developing fully folded peptoid protein structures.
The cis/trans amide bond isomerization still leads to a conformational heterogeneity which doesn’t allow for the formation of homogeneous peptoid foldamers. Nonetheless scientists were able to find trans-inducer "N"-Aryl side chains promoting polyproline type II helix, and strong cis-inducer such as bulky naphtylethyl and tert-butyl side chains. It was also found that n→π* interactions can modulate the ratio of cis/trans amide bond conformers, until reaching a complete control of the cis conformer in the peptoid backbone using a functionalizable triazolium side chain.
Applications.
The first demonstration of the use of peptoids was in screening a combinatorial library of diverse peptoids which yielded novel high-affinity ligands for 7-transmembrane G-protein-couple receptors.
Peptoids have been developed as candidates for a range of different biomedical applications, including antimicrobial agents and synthetic lung surfactants, as well as ligands for various proteins including Src Homology 3 (SH3 domain), Vascular Endothelial Growth Factor (VEGF) receptor 2, and antibody Immunoglobulin G biomarkers for the identification of Alzheimer's disease.
Due to their advantageous characteristics as described above, peptoids are also being actively developed for use in nanotechnology, an area in which they may play an important role.


Methylpropyltryptamine

Methylpropyltryptamine (MPT; "N"-methyl-"N"-propyltryptamine) is a tryptamine. It is a homolog of methylethyltryptamine.
An analytical method for its detection has been reported.
In 2019, Chadeayne et al. published the crystal structure of MPT. The authors describe the structure as "...a single molecule in the asymmetric unit, with an indole group that demonstrates a mean deviation from planarity of 0.015 A°."


Lucihormetica luckae

Lucihormetica luckae is a species of giant cockroach (Blaberidae) from Ecuador.
Light production.
Like other species in the genus "Lucihormetica", "L. luckae"s back carapace features one small and two large spots that glow when exposed to light (autofluorescence), perhaps to mimic the appearance of the toxic click beetle ("Pyrophorus") that emits light at the same wavelength, in which case this would be an instance of Batesian mimicry. The evidence for genuine bioluminescence in "Lucihormetica" cockroaches is anecdotal and inconclusive, though there is evidence for autofluorescence.
Status.
The species may be threatened, or even extinct, as only one specimen has ever been collected, some 70 years ago. In addition Tungurahua, the Ecuadorian volcano that served as the species' habitat, entered a new eruptive phase in 1999.
The species was listed among the "Top 10 New Species 2012" as selected by the International Institute for Species Exploration at Arizona State University out of more than 140 nominated species.
In human culture.
The back shell of "L. luckae" has been noted for its resemblance to Jawas, fictional creatures from the "Star Wars" science fiction media franchise.


Azor Betts

Azor Betts (September 13, 1740 – September 14, 1809) was an American Loyalist doctor who began his practice in the Province of New York before the American Revolutionary War. His staunch defense of smallpox inoculation and support of the Loyalist cause led to his arrest and eventual departure to Canada.
Life before the Revolution.
Azor Betts was born on September 13, 1740, in Norwalk, Connecticut, the son of Nathan Betts and Mary Belden. He married Gloriana Purdy in 1765 in Rye, New York, and practiced medicine in New York City prior to the Revolutionary War.
The Revolution and smallpox.
The events of 1776 that began open hostility between the Continental Army and the British Army in America were tempered by outbreaks of smallpox that began the year previous. General George Washington of the Continentals ordered on May 20, 1776, that no man in his army be inoculated with smallpox, or face serious punishment. Betts first administered smallpox to members of the Continental Army mere days after the order was given, and was placed under arrest by local authorities. Testimony during a hearing on the matter before the New York Committee of Safety on May 26, 1776, was given by both Doctor Foster representing the prosecution and Betts in his defense. Doctor Foster testified that:
In his defense, Betts told the Committee that:
As a reaction to the news that Betts had performed these inoculations in New York, Washington, immediately drew up another order, this time spelling out the punishment for any soldier caught being inoculated with smallpox:
Jailed again for more smallpox inoculations, Betts became an open Loyalist, serving as both a Captain-Lieutenant in the Kings American Regiment and also as a surgeon for the Queen's Rangers. In May 1783, Betts left America for good, making his home in Kingston, New Brunswick.
Life in Canada.
Soon after arriving in Kingston, Betts created isolation wards for those infected with smallpox. He continued this practice, and when the smallpox vaccine was introduced in 1802, he vaccinated local citizens free of charge.
Betts died of consumption in Digby, Nova Scotia, in 1809, one day after his 69th birthday. He is buried in the cemetery of the Trinity Anglican Church there.
The inscription on a tombstone erected and later renewed by his family cites a different date for his death and burial place. A grave stone at the Old Loyalist Burial Grounds in Saint John, New Brunswick, is inscribed "In Memory of Dr Azor Betts Died Sept 15, 1811, aged 72 years. Also his wife Gloriannah, died March 16, 1815, aged 68 years."


William C. Van Buskirk

William C. Van Buskirk was the Provost and Senior Vice President for Academic Affairs of New Jersey Institute of Technology (NJIT) in Newark, New Jersey from Oct 1998 to June 2004., and he retired in December 2011 as a Distinguished Professor in the Department of Biomedical Engineering and was the Foundation Professor of Biomechanical Engineering at NJIT.
Education.
Van Buskirk received his BS in 1964 from the United States Military Academy, an MS in 1966 and his PhD in 1970 in Aeronautical and Astronautical Engineering from Stanford University.
Career.
Following his PhD, Van Buskirk started as an assistant professor of Mechanical Engineering at Tulane University. He developed the undergraduate program in Biomedical Engineering there and rose to head of department and endowed chair positions before becoming the Dean of the School of Engineering. He left Tulane University in 1998 to become the Provost and Senior Vice President for Academic Affairs at the New Jersey Institute of Technology.
During his almost six years term as the Provost at NJIT, he was involved with the creation of the Biomedical Engineering department, the movement of the Chemistry and Environmental Science faculty to the College of Science and Liberal Arts and the evolution of the Computer and Information Science department into the College of Computing Sciences. He stepped back to teaching and research roles as a Distinguished Professor in the Biomedical Engineering department in 2004.


Trilochan Mohapatra

Trilochan Mohapatra (born 20 April 1962) is an Indian biotechnologist, geneticist, a government secretary of the Department of Agricultural Research and Education (DARE) and the director general of the Indian Council of Agricultural Research. Known for his studies in the fields of molecular genetics and genomics, Mohapatra is an elected fellow of the National Academy of Sciences, India, the National Academy of Agricultural Sciences, the Indian National Science Academy and the Indian Society of Genetics and Plant Breeding. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to biosciences in 2003.
Biography.
Trilochan Mohapatra was born on 20 April 1962 at Kharibil village in Cuttack in the Indian state of Odisha. After completing early schooling at Laxmi Narayan High School at Eranch near his home village in 1978, he did his pre-university studies at Ravenshaw College (present day Ravenshaw University) in 1980. Joining Orissa University of Agriculture and Technology (OUAT), he earned a BSc in agriculture in 1985 as well as an MSc in genetics in 1987 and continued at the institution for his doctoral studies to secure a PhD in 1992. He started his career in 1992 as a senior scientist at the National Research Centre on Plant Biotechnology (NRCPB), a centre of the Indian Agricultural Research Institute (IARI) for advanced research in the fields of molecular biology and biotechnology in crop plants where he worked until 2012, serving as a principal scientist from 2005. In between, he did advanced training in rice genome sequencing at the Arizona Genomics Institute of the University of Arizona during 2003–04. In 2012, he was appointed as the director of Central Rice Research Institute as well as the vice-chancellor of the Indian Agricultural Research Institute. He served as the director of IARI in the year 2015-16 and on 22 February 2016, he was appointed as the secretary of the Department of Agricultural Research and Education (DARE), a department working under the Ministry of Agriculture to act as the government interface for promoting agricultural research and education in India. Simultaneously, He holds the position of the director general of the Indian Council of Agricultural Research.
Dr. Mohapatra is married and the family resides at National Agriculture Science Centre (NASC) Complex along Dev Prakash Shastri Marg in New Delhi.
Legacy.
Mohapatra, whose research interests covered the fields of molecular genetics and genomics, is known to have worked on the bacterial sequencing of rice and tomato and is credited with the development of a high-yielding basmati rice which is resistant to bacterial leaf blight which was accomplished using "molecular marker assisted selection, physical mapping and genome sequencing". Molecular mapping of genome and tagging of gene in mustard, molecular mapping and gene isolation in Basmati rice hybrid, marker assisted selection for powdery mildew resistance in pea, molecular marker analysis of sugarcane, identification of pearl millet hybrids, sex differentiation of kiwifruit employing Random Amplification of Polymorphic DNA technique and evaluation of genetic diversity of jute were some of the other research projects he has undertaken, and he holds several patents for the processes he has developed. His studies have been documented by way of a number of articles and ResearchGate, an online repository of scientific articles has listed 182 of them. He has also guided several students in their doctoral and master's studies and has imparted training on molecular breeding to over 25 scientists.
As the head of the Indian Council of Agricultural Research, Mohapatra is in charge of 101 ICAR institutes and 71 agricultural universities, spread across India. He sits in the council of the National Academy of Agricultural Sciences and is a member of the executive committee of Borlaug Institute for South Asia. He served as an expert on "Germplasm Characterization" at the National Institute of Agricultural Biotechnology, Korea, having received an invitation from the National Institute of Agricultural Biotechnology (NIAB), in 2004. He is a life member of the Indian Society of Genetics and Plant Breeding and the Society of Plant Biochemistry and Biotechnology. He is also a former associate editor of BMC Genetics and the Journal of Genetics.
Awards and honors.
Mohapatra received two awards from the Indian National Science Academy in 1994, namely INSA Young Scientist Medal and Professor LSS Kumar Memorial Award. He was selected for the NAAS-Tata Young Scientist Award of the National Academy of Agricultural Sciences (NAAS) in 2001; he also received two other honors from NAAS, the elected fellowship in 2006 and the Recognition Award in 2016. The next year, the Indian Agricultural Research Institute selected him for the B. P. Pal Memorial Award. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards in 2003. The Indian Society of Genetics and Plant Breeding elected him as a fellow in 2004 and he received the elected fellowships of the National Academy of Sciences, India in 2005 and the Indian National Science Academy in 2013. The National Academy of Sciences, India honored him again in 2007 with the NASI-Reliance Platinum Jubilee Award and he received the Lifetime Achievement Award at the Indian Genetics Congress of 2015. He is also a recipient of the Bioved Agri-Innovation Award of 2015 and the Om Prakash Bhasin Award and the IMS Diamond Jubilee Memorial Award, both in 2016. The award orations delivered by him include the Prasanna Kumar Dash Memorial Lecture of the Orissa Environmental Society (2013), Dr. Gopal Chandra Patnaik Memorial Lecture of the Bigyan Prachar Samiti (2013), Platinum Jubilee Lecture Award of 101st Indian Science Congress (2014) and the inaugural Prof. S.N. Patnaik Memorial Lecture of Utkal University (2014).
Honorary D.Sc degree on 7th convocation ceremony by Mahatma Gandhi Chitrakoot Gramodaya Vishwavidhyala, Chitrakoot Satna.


GenSpera

Inspyr Therapeutics, Inc. (OTC: NSPX) is a development-stage pharmaceutical company based in San Antonio, Texas. The company is focused on therapeutics that deliver a cancer-destroying drug directly to the tumor or its supporting environment, the tumor vasculature.
The company's prodrug technology renders the drug inactive until it encounters the programmed target, thereby delivering the cytotoxin directly to the cancer or the vessels that support it, while potentially avoiding the side effects associated with current chemotherapies. A prodrug is an inactive precursor of a drug that is converted into its active form at a targeted site.
GenSpera's lead drug candidate, G-202, is currently in a Phase II clinical trial for patients with hepatocellular carcinoma (HCC) whose disease has failed to improve on standard therapy for this indication. G-202 is also being evaluated in a Phase II clinical trial in glioblastoma patients with recurrent disease after surgery and/or radiation treatment of the primary tumor. G-202 targets the enzyme PSMA, found on the walls of blood vessels that feed most cancerous tumors, destroying the tumor blood supply. In contrast with anti-angiogenic agents, G-202 destroys existing as well as new cancer blood vessels. G-202 received Orphan Drug Designation from U.S. Food and Drug Administration for the treatment of HCC, the most common form of primary liver cancer.
The company also holds patents on prodrug candidates that target the prostate-specific enzymes Prostate Specific Antigen (PSA) and Human Glandular Kallikrein (hK2). These candidates are expected to be useful in the treatment of prostate cancer.
The active ingredient in G-202 is a chemotherapeutic agent derived from thapsigargin, a plant-based cytotoxin that kills by disrupting the calcium balance in cancer cells. GenSpera's prodrug delivery system keeps the thapsigargin inactive in the body until it finds cells that it has been programmed to seek. Once those cells in the body are found, the prodrug releases its active ingredient and destroys all of the targeted cells.
The National Cancer Institute had previously demonstrated that thaspigargin was ten-to-a-hundredfold more potent than traditional chemotherapeutic agents in killing all types of cells. Thapsigargin kills cells irrespective of the rate of cell division, which may provide an effective approach to kill both fast- and slow-growing cancers as well as cancer stem cells.
History.
In 1992, Professor John T. Isaacs of The Johns Hopkins School of Medicine in Baltimore, Maryland, was investigating ways to approach the treatment of slow-growing tumors and discovered they could be efficiently destroyed if intracellular calcium levels were raised significantly. He determined that the ideal agent for upsetting intracellular calcium levels was the novel chemical thapsigargin. He began collaborating with Dr. Soren Christensen, a natural products chemist, at the University of Copenhagen in Denmark, and the first scientist to isolate thapsigargin from the plant "Thapsia garganica", a poisonous weed that grows wild in areas of the Mediterranean. The objective of the collaboration was to chemically alter thapsigargin to a derivative that could be linked to peptides, thus forming prodrugs to treat certain tumors.
Drs. Isaacs and Christensen were joined in their research by Dr. Hans Lilja, now at the Memorial Sloan-Kettering Cancer Center in New York, and Dr. Samuel Denmeade, of the Johns Hopkins School of Medicine. Together the four co-inventors developed a technology platform in which the therapeutic component of all the compounds would remain the same, but the targeting peptide would change. Peptides would be selected that could only be "cut off" or cleaved by enzymes specific for certain tumors.
On August 1 2016 the company changed its name to "Inspyr Therapeutics".
The company.
GenSpera president and CEO Craig Dionne, PhD, co-founded GenSpera in 2003. He was previously vice president of biological research at Cephalon Inc., where he was responsible for neurobiology and oncology drug discovery. GenSpera was financed by a series of private placements beginning in 2007 and became publicly traded in late 2009.


Transmembrane channels

Transmembrane channels, also called membrane channels, are pores within a lipid bilayer. The channels can be formed by protein complexes that run across the membrane or by peptides. They may cross the cell membrane, connecting the cytosol, or cytoplasm, to the extracellular matrix. Transmembrane channels are also found in the membranes of organelles including the nucleus, the endoplasmic reticulum, the Golgi apparatus, mitochondria, chloroplasts, and lysosomes.
Transmembrane channels differ from transporters and pumps in several ways. Some channels are less selective than typical transporters and pumps, differentiating solutes primarily by size and ionic charge. Channels perform passive transport of materials also known as facilitated diffusion. Transporters can carry out either passive or active transfer of materials while pumps require energy to act.
There are several modes by which membrane channels operate. The most common is the gated channel which requires a trigger, such as a change in membrane potential in voltage-gated channels, to unlock or lock the pore opening. Voltage-gated channels are critical to the production of an action potential in neurons resulting in a nerve impulse. A ligand-gated channel requires a chemical, such as a neurotransmitter, to activate the channel. Stress-gated channels require a mechanical force applied to the channel for opening. Aquaporins are dedicated channels for the movement of water across the hydrophobic interior of the cell membrane.
Ion channels are a type of transmembrane channel responsible for the passive transport of positively charged ions (sodium, potassium, calcium, hydrogen and magnesium) and negatively charged ions (chloride) and, can be either gated or ligand-gated channels. One of the best studied ion channels is the potassium ion channel. The potassium ion channel can allow rapid movement of potassium ions while being selective against sodium. Using X-ray diffraction data and atomic model computations a likely structure of the channel consists of a number of protein alpha-helixes forming an hourglass shaped pore with the narrowest point halfway through the membrane's lipid bilayer. To move through the channel the potassium ions must shed their aqueous matrix and enter a selectivity filter composed of carbonyl oxygens. The potassium ions pass through one atom at a time along five different cation (positively charged ion) binding sites.
Diseases caused by ion channel malfunctions include cystic fibrosis where the channel for the chloride ion will not open or is missing in the cells of the lungs, intestine, pancreas, liver and skin. The cells can no longer regulate salt and water concentrations resulting in the symptoms typical of the disease. Additional disorders resulting from malfunctions in ion channels include forms of epilepsy, cardiac arrhythmia, certain types of periodic paralysis and ataxia.


Emerald Cloud Lab

Emerald Cloud Lab (ECL) is a privately-owned biotech startup. The company focuses on advancing laboratory virtualization, for chemistry and biotechnology, by building the first fully functional cloud lab, allowing scientists to conduct all of their wet lab research without being in a physical laboratory.
Products and Services.
ECL is a physical laboratory that can be accessed remotely by scientists via the internet. Scientists ship samples to an ECL facility and design their experiments in the ECL Command Center software application. ECL Command Center is a fully integrated application, where experiments are encoded in a language and grammar designed by ECL to allow remote operation and ensure reproducibility. ECL remotely conducts your experiments in a highly automated ECL facility exactly to the scientist’s specifications. The platform collects and organizes all data generated by and relevant to experiments into a powerful knowledge graph. ECL Command Center’s extensive suite of tools can then be used to plot, analyze, and visualize results.
History.
Founding.
D.J. Kleinbaum and Brian Frezza grew up together on Emerald Drive outside of Philadelphia. In 2010, after completing their PhDs, they came together to found Emerald Therapeutics in an effort to develop "antiviral therapeutics for diseases such as HPV and HIV". During this time, they experienced frustrations with laboratory hardware and software. Hardware often comes from disparate manufacturers, software is often rudimentary, and output can vary in formatting. To simplify laboratory testing, the group wrote centralized management software for the different machines and a database to store all metadata and results. This "laboratory operating system" continued to expand in capabilities, including the ability to directly control instrumentation and manage inventory and procurement. Recognizing the value this type of system presented outside of their own development goals, Kleinbaum and Frezza launched this service in 2014 under the name Emerald Cloud Lab. In 2016, Emerald Cloud Lab and Emerald Therapeutics were spun off from one another, and both are independent corporations.
Business development.
As of 2014, Emerald Cloud Lab offered access to 40 types of laboratory instruments. By 2017, the range of instruments had expanded to 106. As of July 2020, Emerald Cloud Lab offered full control of over 150 laboratory instruments, with plans to expand capabilities outlined through 2021.
Researchers and pharmaceutical groups have long been concerned about the lack of reproducibility of laboratory testing in the biomedical field. A 2017 literature analysis article posited that highly automated, internet connected labs like ECL could ameliorate the problem. The paper concludes that, "we believe that robotic labs can provide the basis for performing a large percentage of basic biomedical research in a reproducible and transparent fashion". Frezza has described this laboratory inconsistency as one specific reason for the development of Emerald Cloud Lab and the use of automation.
Financing.
After spinning out of Emerald Therapeutics, the company has gone on to raise capital in multiple rounds. Key investors include Founders Fund, Schooner Capital, OS Fund, Alcazar Capital, Western Technology Investment, Sound Ventures, SciFi VC, Incite Ventures, and Spike Ventures.
The business got its second round of funding by 2014 from the Founders Fund (FF), a venture capital firm founded by Peter Thiel, bringing total funding raised from FF up to $13.5 million. The first FF funding round was not public.


Pepducin

Pepducins are cell-penetrating peptides that act as intracellular modulators of signal transference from receptors to G proteins. Pepducins were first developed at the Tufts Medical Center laboratories of Dr. Athan Kuliopulos and Dr. Lidija Covic.
Pepducins employ lipidated fragments of intracellular G protein-coupled receptor loops to modulate GPCR action in targeted cell-signaling pathways. A pepducin molecule consists of a short peptide derived from a GPCR intracellular loop tethered to a hydrophobic moiety. This structure allows pepducin lipopeptides to anchor in the cell membrane lipid bilayer and target the GPCR/G protein interface via a unique intracellular allosteric mechanism. Pepducins for over 15 different GPCRs have been successfully produced, several of which have shown activity in preclinical "in vivo" models.
An anti-PAR4 pepducin extended bleeding time in mice and protected against systemic platelet activation and thrombosis.
A CXCR4 agonist pepducin mobilizes bone marrow hematopoietic cells.
A PAR1 pepducin, PZ-128, has successfully completed phase I clinical trials.


Rogelio Pfirter

Rogelio Pfirter is an Argentine diplomat. He was the Director General of the Organisation for the Prohibition of Chemical Weapons (OPCW) from 2002 to 2010. Pfirter was born in Santa Fe, Argentina, on 25 August 1948. He graduated as a lawyer from the Universidad Nacional del Litoral (Argentina). He is married to Isabel Serantes Braun.
Professional career.
During his diplomatic career, Pfirter held various positions at the Argentine Foreign Ministry. In 1992 he was promoted to the rank of Ambassador and in the same year he became the Director of the Argentine-Brazilian Agency for Accounting and Control of Nuclear Materials (ABACC) and the Director of the Argentine Space Agency (CONAE). He was subsequently appointed Undersecretary for Foreign Policy at the Argentine MFA.
In 2002, Pfirter was unanimously elected the Director-General of the Organisation for the Prohibition of Chemical Weapons (OPCW) in The Hague, The Netherlands. He was elected for a second term in 2006. Pfirter’s tenure was praised as a time of consolidation and strengthening of the OPCW after the controversial departure of his predecessor José Bustani. Pfirter gathered support for chemical weapons destruction and as a manager he succeeded in administering the Secretariat with zero nominal growth (ZNG) for four years in a row.
After retiring in 2010, he became a member of the Global Council on Weapons of Mass Destruction at the World Economic Forum.
Awards.
Pfirter has received a number of international awards including Grand Cross of the Orden of Merit from Chile as well as Germany; Officier of the Legion of Honour from France and Commandeur of the Order of Orange-Nassau from the Netherlands.


Arthrobacter

Arthrobacter (from the Greek, "jointed small stick”) is a genus of bacteria that is commonly found in soil. All species in this genus are Gram-positive obligate aerobes that are rods during exponential growth and cocci in their stationary phase. "Arthrobacter" have a distinctive method of cell division called "snapping division" or reversion in which the outer bacterial cell wall ruptures at a joint.
Description.
"Arthrobacter" can be grown on mineral salts pyridone broth, where colonies have a greenish metallic center on incubated at . Under the microscope, "Arthrobacter" appear as rods when rapidly dividing, and cocci when in stationary phase. Dividing cells may also appear as chevrons ("V" shapes). Other notable characteristics are that it can use pyridone as its sole carbon source, and that its cocci are resistant to desiccation and starvation.
Use in industry.
"Arthrobacter", like other bacterial genera including "Brevibacterium", "Microbacterium", and "Corynebacterium" are used for industrial production of L-glutamate. In industrial applications, "Arthrobacter" is often grown with low-cost sugar sources such as cane or beet molasses, starch hydrolysates from corn or cassava tubers, or tapioca. Along with sugar, ammonia and ammonium salts are added as a nitrogen source. The vitamins, minerals, and some other types of nutrients can be provided by adding corn steep liquour.
Other uses.
Various "Arthrobacter" species have been investigated for other commercial applications. "A. crystallopoietes" and "A. chlorophenolicus" have been shown to reduce hexavalent chromium and 4-chlorophenol levels in contaminated soil, suggesting they may be useful for bioremediation. Similarly, "Arthrobacter" sp. strain R1 (American Type Culture Collection strain number 49987) has been shown to grow on a variety of aromatic compounds, including homocyclic compounds, such as hydroxybenzoates, as well as N-heterocycles, including pyridine and picoline.
"Arthrobacter" sp H65-7 produces the enzyme inulase II that converts inulin into the medically-relevant nutrient difructose anhydride.
The enzyme Alu obtained from "Arthrobacter luteus" is able to cleave Alu sequences which is frequently repeated in human DNA.


Activin receptor

An Activin receptor is a receptor which binds activin.
Types include:
These proteins are receptor-type kinases of Ser/Thr type, which have a single transmembrane domain and a specific hydrophilic Cys-rich ligand-binding domain.
Human proteins containing this domain.
ACVR1; ACVR1B; ACVR1C; ACVR2A; ACVR2B; ACVRL1; BMPR1A; BMPR1B;
BMPR2; TGFBR1;


Gene amplification

Gene amplification refers to a number of natural and artificial processes by which the number of copies of a gene is increased "without a proportional increase in other genes".
Artificial DNA amplification.
In research or diagnosis DNA amplification can be conducted through methods such as:
Natural DNA amplification.
DNA replication is a natural form of copying DNA with the amount of genes remaining constant. However, the amount of DNA or the number of genes can also increase within an organism through gene duplication, a major mechanism through which new genetic material is generated during molecular evolution. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.
A piece of DNA or RNA that is the source and/or product of either natural or artificial amplification or replication events is called an amplicon.


Dopamine agonist

A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are used in Parkinson’s disease and, to a lesser extent, to treat depression, hyperprolactinemia and restless legs syndrome.
Medical uses.
Parkinson's disease.
Dopamine agonists are mainly used in the treatment of Parkinson's disease.  The cause of Parkinson's is not fully known but genetic factors, for example specific genetic mutations, and environmental triggers have been linked to the disease. In Parkinson's disease dopaminergic neurons that produce the neurotransmitter dopamine in the brain slowly break down and can eventually die. With decreasing levels of dopamine the brain can't function properly and causes abnormal brain activity, which ultimately leads to the symptoms of Parkinson's disease.
There are two fundamental ways of treating Parkinson's disease, either by replacing dopamine or mimicking its effect.
Dopamine agonists act directly on the dopamine receptors and mimick dopamine's effect. Dopamine agonists have two subclasses: ergoline and non ergoline agonists. Both subclasses target dopamine D2-type receptors. Types of ergoline agonists are cabergoline and bromocriptine and examples of non-ergoline agonists are pramipexole, ropinirole and rotigotine. Ergoline agonists are much less used nowadays because of the risk of cartilage formation in heart valves.
Treatment of depression in Parkinson's patients.
Depressive symptoms and disorders are common in patients with Parkinson's disease and can affect their quality of life. Increased anxiety can accentuate the symptoms of Parkinson's and is therefore essential to treat. Instead of conventional antidepressant medication in treating depression, treatment with dopamine agonists has been suggested. It is mainly thought that dopamine agonists help with treating depressive symptoms and disorders by alleviating motor complications, which is one of the main symptoms of Parkinson's disease.  Although preliminary evidence of clinical trials has shown interesting results, further research is crucial to establish the anti-depressive effects of dopamine agonists in treating depressive symptoms and disorders in those with Parkinson's.
Hyperprolactinemia.
Dopamine is a prolactin-inhibiting factor (PIFs) since it lowers the prolactin-releasing factors (PRFs) synthesis and secretion through DD2-like receptors. That is why dopamine agonists are the first-line treatment in hyperprolactinemia. Ergoline-derived agents, bromocriptine and cabergoline are mostly used in treatment. Research shows that these agents reduce the size of prolactinomas by suppressing the hypersecretion of prolactin resulting in normal gonadal function.
Restless leg syndrome.
Numerous clinical trials have been performed to assess the use of dopamine agonists for the treatment of restless leg syndrome (RLS). RLS is identified by the strong urge to move and is a dopamine-dependent disorder. RLS symptoms decrease with the use of drugs that stimulate dopamine receptors and increase dopamine levels, such as dopamine agonists.
Adverse effects.
Side effects.
Dopamine agonists are mainly used to treat Parkinson’s disease but are also used to treat hyperprolactinemia and restless legs syndrome. The side effects are mainly recorded in treatment for Parkinson’s disease where dopamine agonists are commonly used, especially as first-line treatment with levodopa.
Dopamine agonists are divided into two subgroups or drug classes, first-generation and newer agents. Ergoline derived agonists are the first generation and are not used as much as the newer generation the non-ergoline derived agonists. Ergoline derived agonists are said to be dirtier drugs because of their interaction with other receptors than dopamine receptors, therefore they cause more side effects. Ergoline derived agonists are for example bromocriptine, cabergoline, pergolide and lisuride. Non-ergoline agonists are pramipexole, ropinirole, rotigotine, piribedil and apomorphine.
The most common adverse effects are constipation, nausea and headaches. Other serious side effects are hallucinations, peripheral edema, gastrointestinal ulcers, pulmonary fibrosis and psychosis.
Dopamine agonists have been linked to cardiac problems. Side effects such as hypotension, myocardial infarction, congestive heart failure, cardiac fibrosis, pericardial effusion and tachycardia. A high risk for valvular heart disease has been established in association with ergot-derived agonists especially in elderly patients with hypertension.
Somnolence and sleep attacks have been reported as an adverse effect that happen to almost 30% of patients using dopamine agonists. Daytime sleepiness, insomnia and other sleep disturbances have been reported as well.
Impulse control disorder that is described as gambling, hypersexuality, compulsive shopping and binge eating is one serious adverse effect of dopamine agonists.
After long-term use of dopamine agonist a withdrawal syndrome may occur when discontinuing or during dose reduction. The following side effects are possible: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalised pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years.
Interactions.
Dopamine agonists interact with a number of drugs but there is little evidence that they interact with other Parkinson’s drugs. In most cases there is no reason not to co-administer Parkinson's drugs. Although there has been an indication that the use of dopamine agonists with L-DOPA can cause psychosis therefore it is recommended that either the use of dopamine agonists be discontinued or the dose of L-DOPA reduced. Since ergot-dopamine agonist have antihypertensive qualities it is wise to monitor blood pressure when using dopamine agonists with antihypertensive drugs to ensure that the patient does not get hypotension. That includes the drug sildenafil which is commonly used to treat erectile dysfunction but also used for pulmonary hypertension.
There is evidence that suggests that since ergot dopamine agonists are metabolized by CYP3A4 enzyme concentration rises with the use of CYP3A4 inhibitors. For example, in one study bromocriptine was given with a CYP3A4 inhibitor and the AUC (e. Area under the curve) increased 268%. Ropinirole is a non-ergot derived dopamine agonist and concomitant use with a CYP1A2 inhibitor can result in a higher concentration of ropinirole. When discontinuing the CYP1A2 inhibitor, if using both drugs, there is a change that a dose adjustment for ropinirole is needed. There is also evidence the dopamine agonists inhibit various CYP enzymes and therefore they may inhibit the metabolism of certain drugs.
Pharmacology.
Ergoline class.
Pharmacokinetics of Bromocriptine.
The absorption of the oral dose is approximately 28% however, only 6% reaches the systemic circulation unchanged, due to a substantial first-pass effect. Bromocriptine reaches mean peak plasma levels in about 1–1.5 hours after a single oral dose. The drug has high protein binding, ranging from 90-96% bound to serum albumin. Bromocriptine is metabolized by CYP3A4 and excreted primarily in the feces via biliary secretion. Metabolites and parent drugs are mostly excreted via the liver, but also 6% via the kidney. It has a half-life of 2–8 hours.
Pharmacokinetics of Pergolide.
Pergolide has a long half-life of about 27 hours and reaches a mean peak plasma level in about 2–3 hours after a single oral dose. The protein binding is 90% and the drug is mainly metabolized in the liver by CYP3A4 and CYP2D6. The major route of excretion is through the kidneys.
Non-Ergoline class.
Pharmacokinetics of Pramipexole.
Pramipexole reaches maximum plasma concentration 1–3 hours post-dose. It is about 15% bound to plasma proteins and the metabolism is minimal. Pramipexole has a long half-life, around 27 hours. The drug is mostly excreted in the urine, around 90%, but also in feces.
Pharmacokinetics of Ropinirole.
Ropinirole is rapidly absorbed after a single oral dose, reaching plasma concentration in approximately 1–2 hours. The half-life is around 5–6 hours. Ropinirole is heavily metabolized by the liver and in vitro studies show that the enzyme involved in the metabolism of ropinirole is CYP1A2.
Pharmacokinetics of Rotigotine.
Since rotigotine is a transdermal patch it provides continuous drug delivery over 24 hours. It has a half-life of 3 hours and the protein binding is around 92% in vitro and 89.5% in vivo. Rotigotine is extensively and rapidly metabolized in the liver and by the CYP enzymes. The drug is mostly excreted in urine (71%), but also in feces (23%).
Mechanism of action.
The dopamine receptors are 7-transmembrane domains and are members of the G protein-coupled receptors (GPCR) superfamily. Dopamine receptors have five subtypes, D1 through D5, the subtypes can be divided into two subclasses due to their mechanism of action on adenylate cyclase enzyme, D1-like receptors (D1 and D5) and D2-like receptors (D2, D3 and D4). D1-like receptors are primarily coupled to Gαs/olf proteins and activates adenylate cyclase which increases intracellular levels of cAMP, they also activate the Gβγ complex and the N-type Ca2+ channel. D2-like receptors decrease intracellular levels of the second messenger cAMP by inhibiting adenylate cyclase.
Bromocriptine.
Bromocriptine is an ergot derivative, semi-synthetic. Bromocriptine is a D2 receptor agonist and D1 receptor antagonist with a binding affinity to D2 receptors of anterior pituitary cells, exclusively on lactotrophs. Bromocriptine stimulates Na+, K+-ATPase activity and/or cytosolic Ca2+ elevation and therefore reduction of prolactin which leads to no production of cAMP.
Pramipexol.
Pramipexol is a highly active non-ergot D2-like receptor agonist with a higher binding affinity to D3 receptors rather than D2 or D4 receptors. The mechanism of action of pramipexole is mostly unknown, it is thought to be involved in the activation of dopamine receptors in the area of the brain where the striatum and the substantia nigra is located. This stimulation of dopamine receptors in the striatum may lead to the better movement performance.
Structure–activity relationship.
When dealing with agonists it can be extremely complex to confirm relationships between structure and biological activity. Agonists generate responses from living tissues. Therefore, their activity depends both on their efficacy to activate receptors and their affinity to bind to receptors.
Crossing the blood brain barrier.
Many molecules are unable to cross the blood brain barrier (BBB). Molecules must be small, non-polar and lipophilic to cross over. If compounds do not possess these qualities they must have a specific transporter that can transport them over the BBB. Dopamine cannot diffuse across the BBB because of the catechol group, it is too polar and therefore unable to enter the brain. The catechol group is a dihydroxy benzene ring.
The synthesis of dopamine consists of three stages. The synthesis process starts with an amino acid, called L-Tyrosine. In the second stage Levodopa (L-dopa) is formed by adding a phenol group to the benzene ring of L-Tyrosine. The formation of L-dopa from L-tyrosine is catalyzed by the enzyme tyrosine hydroxylase. The third stage is the formation of dopamine by removing the carboxylic acid group from L-dopa, catalysed by the enzyme dopa decarboxylase.
Levodopa is also too polar to cross the blood brain barrier but it happens to be an amino acid so it has a specialized transporter called L-type amino acid transporter or LAT-1 that helps it diffuse through the barrier.
Dopamine.
When dopamine interacts with ATP, which is a component of some dopamine receptors, it has a significant preference for a trans-conformation of the dopamine molecule. The dopamine-ATP complex is stabilised by hydrogen bonding between catechol hydroxyls and purine nitrogens and by electrostatic interactions between the protonated ammonium group of dopamine and a negative phosphate group. Two conformers of dopamine have been identified as alpha- and beta-conformers in which the catechol ring is coplanar with the plane of the ethylamine side chain. They are substantial in agonist-receptor interactions.
Ergoline derivatives.
Central dopaminergic agonist properties of semisynthetic ergoline derivatives lergotrile, pergolide, bromocriptine and lisuride have been established. Some studies suggest that ergot alkaloids have the properties of mixed agonist-antagonist with regards to certain presynaptic and postsynaptic receptors. N-n-Propyl groups (chemical formula: –CH2CH2CH3) frequently enhance dopamine agonist effects in the ergoline derivatives.
The (+)-enantiomer displays notably diminished activity whereas the (-)-enantiomer possess potent dopamine agonist properties.
"Bromocriptine".
Bromocriptine has an ergot alkaloid structure. Ergot alkaloids are divided into 2 groups; amino acid ergot alkaloids and amine ergot alkaloids, bromocriptine is part of the former group. It contains a bromine halogen on the ergot structure which increases the affinity for the D2-receptor but often reduces the efficacy. The similarity between the dopamine structure and the ergoline ring in bromocriptine is likely the cause for its action on the dopamine receptors. It has shown to have equal affinity for D2- and D3-receptor and much lower affinity for D1-receptor.
Non-ergoline derivatives.
Non-ergoline dopamine receptor agonists have higher binding affinity to dopamine D3-receptors than dopamine D2-receptors. This binding affinity is related to D2 and D3 receptor homology, the homology between them has a high degree of sequence and is closest in their transmembrane domains, were they share around 75% of the amino acid.
"Apomorphine".
Apomorphine has a catechol element and belongs to a class called β-phenylethylamines and its main components are similar to the dopamine structure. The effect that apomorphine has on the dopamine receptors can also be linked to the similarities between its structure and dopamine. It is a chiral molecule and thus can be acquired in both the R and S form, the R form is the one that is used in therapy. When apomorphine interacts with the dopamine receptor, or the ATP on the receptor, the catechol and nitrogen are important to stabilize the structure with hydrogen bonding. The position of the hydroxyl groups is also important and monohydroxy derivatives have been found to be less potent than the dihydroxy groups. There are a number of stability concerns with apomorphine such as oxidation and racemization.
"Rotigotine".
Rotigotine is a phenolic amine and thus has poor oral bioavailability and fast clearance from the body. Therefore, it has been formulated as a transdermal patch, first and foremost to prevent first pass metabolism in the liver.
Members.
Examples of dopamine agonists include:
Agonists of full/unknown efficacy.
Some, such as fenoldopam, are selective for dopamine receptor D1.
Indirect agonists.
There are two classes of drugs that act as indirect agonists of dopamine receptors: dopamine reuptake inhibitors and dopamine releasing agents.
The most commonly prescribed indirect agonists of dopamine receptors include:
Other examples include:
History.
Since the late 1960 Levodopa (L-DOPA) has been used to treat Parkinson’s disease but there has always been a debate whether the treatment is worth the side effects. Around 1970 clinicians started using the dopamine agonist apomorphine alongside L-DOPA to minimize the side effects caused by L-DOPA, the dopamine agonists bind to the dopamine receptor in the absence of dopamine. Apomorphine had limited use since it had considerable side effects and difficulty with administration. In 1974 bromocriptine was use widely after clinicians discovered its benefits in treating Parkinsons. When using the two drug classes together there is a possibility to reduce the amount of L-DOPA by 20-30% and thus keeping the fluctuating motor responses to a minimum. Dopamine agonists are often used in younger people as monotherapy and as initial therapy instead of L-DOPA. Although it is important to know that there is a correlation between the two drugs, if l-DOPA doesn't work dopamine agonists are also ineffective.
The early dopamine agonists, such as bromocriptine, were ergot derived and activated the D2-receptor. They induced major side effects such as fibrosis of cardiac valves. It is considered that the reason they induced such side effects is that they activate many types of receptors.
Because of the major adverse effects of ergot derived dopamine agonists they are generally not used anymore and were mostly abandoned in favor of non-ergot agonists such as pramipexole, ropinirole and rotigotine. They do not induce as serious side effects although common side effects are nausea, edema and hypotension. Patients have also shown impaired impulse control such as overspending, hypersexuality and gambling.


Francisella small RNAs

Several small RNAs have been identified in "Francisella tularensis," pathogenic bacterium that causes the disease tularaemia. Very little is known about "Francisella's" regulatory networks that allow this bacterium to survive in many environments.
Ftr A and Ftr B ("Francisella tularensis" sRNA A and B) were the first sRNAs identified in "F. tularensis", more specifically in "F. t. holarctica". Experimental analysis confirmed the expression of the well known non-coding RNAs: tmRNA and 4.5S RNA as well as identification of the 2 new sRNAs Ftr A and Ftr B. A genome-wide "in silico" search found several other sRNAs. Ftr A and Ftr B share no sequence similarity or conserved genomic context with any previously annotated regulatory RNAs. Deletion of Ftr A and Ftr B led to significant changes in the expression of several mRNAs. However, it did not alter "Francisella"'s survival during normal growth or under stress conditions. Also deletion of those sRNAs did not affect bacterium ability to induce disease in a mouse model. A major study in "F. t. novicida" later demonstrated FtrA to be associated with a CRISPR/Cas system and to repress an endogenous transcript encoding a bacterial lipoprotein.
FtrC ("Francisella tularensis" sRNA C) is the first sRNA shown to modulate the virulence capacity of "F. tularensis." High expression of FtrC reduces intracellular multiplication of the bacteria in macrophages and in organs of infected mice. FtrC mRNA target gene was also identified, but it is not involved in "Francisella" multiplication.


DHRS7B

Dehydrogenase/reductase (SDR family) member 7B is an enzyme encoded by the DHRS7B gene in humans, found on chromosome 17p11.2. DHRS7B encodes a protein that is predicted to function in steroid hormone regulation. A deletion in the chromosomal region 17p11.2 has been associated with Smith-Magenis Syndrome, a genetic developmental disorder.
Gene.
Overview.
The DHRS7B gene is located on the positive strand of chromosome 17, beginning at position 21030258 and ending at position 21094836 (64579 bp). DHRS7B contains seven exons with no predicted alternate splice forms, resulting in an 1841 bp mRNA product.
Upstream of DHRS7B on the negative strand of chromosome 17p11.2 are the genes "Coiled-coil domain containing 144 family, N-terminal-like" (CCDC144NL) and "Ubiquitin specific peptidase 22" (USP22). Downstream of DHSRS7B on the negative strand of chromosome 17p11.2 is the gene "Transmembrane protein 11" (TMEM11), and on the positive strand is the gene "Mitogen-activated protein kinase, kinase 3" (MAP2K3).
Gene expression.
Microarray and EST data indicates that the DHRS7B gene is highly expressed in the testes, thyroid, kidneys, and adipose tissues. There is moderate expression in the brain, pancreas, mammary glands, and ovaries. Finally, there is little expression in spleen, thymus, tonsils, bone marrow, and bladder.
Protein structure.
The DHRS7B gene has a predicted protein product that is 325 amino acids, a molecular weight of 35.1 kDa, and an isoelectric point of 9.867. There is one predicted transmembrane domain in the protein sequence, a large neutrally charged region spanning residues 18-38. No signal peptides have been identified in DHRS7B; cellular localization remains unclear.
DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR within the protein sequence. The following table identifies sequences in the protein and corresponding function.
Interactions.
In humans, DHRS7B has been shown to physically interact with other proteins such as "Mediator complex subunit 19" (MED19) and "Brain and reproductive expressed-modulator protein" (BRE). MED19 was found to interact with DHRS7B through a two hybrid screening approach and plays a role as a co-activator in regulated transcription of most RNA polymerase II dependent genes. BRE is a component of the BRCA1-A complex, which recognizes Lys-63 linked ubiquitinated histones H2A and H2AX DNA lesion sites (identified using anti-tag coimmunoprecipitation). Other proteins interacting with DHRS7B have only been identified through text mining.
Homology.
Orthologs.
Conservation of the DHRS7B protein sequence has been observed highly in mammals; moderately in reptiles, birds, fish and amphibians; minimally in invertebrates, insects, and fungi.
Paralogs.
Paralogs of DHRS7B are all in the SDR superfamily and conservation of the SDR functional motifs was identified in a multiple sequence alignment.
Clinical significance.
DHRS7B has been identified in the Smith-Magenis Syndrome region, where a deletion in this chromosomal region (17p11.2) causes a genetic developmental disorder. In breast cancer cells expressing CD44 and CD24, DHRS7B expression was observed to be down regulated. CD44 is an antigen found on the surface of most cell types and functions as a receptor that binds tissue macromolecules. Additionally, it acts as an adhesion molecule for leukocytes on peripheral lymphoid organs and inflammation sites. CD24 is associated with B-cells, epithelial cells, and dendritic cells, functioning as an adhesion molecule and shown to enhance a tumor cell's capability of metastasizing.


Lewisite

Lewisite (L) is an organoarsenic compound. It was once manufactured in the U.S., Japan, Germany and the Soviet Union for use as a chemical weapon, acting as a vesicant (blister agent) and lung irritant. Although colorless and odorless, impure samples of lewisite are a yellow, brown, violet-black, green, or amber oily liquid with a distinctive odor that has been described as similar to geraniums.
Chemical reactions.
The compound is prepared by the addition of arsenic trichloride to acetylene in the presence of a suitable catalyst:
Lewisite, like other arsenous chlorides, hydrolyses in water to form hydrochloric acid and chlorovinylarsenous oxide (a less-powerful blister agent):
This reaction is accelerated in alkaline solutions, and forms acetylene and trisodium arsenate.
Lewisite reacts with metals to form hydrogen gas. It is combustible, but difficult to ignite.
Mechanism of action.
Lewisite is a suicide inhibitor of the E3 component of pyruvate dehydrogenase. As an efficient method to produce ATP, pyruvate dehydrogenase is involved in the conversion of pyruvate to acetyl-CoA. The latter subsequently enters the TCA cycle. Peripheral nervous system pathology usually arises from Lewisite exposure as the nervous system essentially relies on glucose as its only catabolic fuel.
It can easily penetrate ordinary clothing and latex rubber gloves. Upon skin contact it causes immediate stinging, burning pain and itching that can last for 24 hours. Within minutes, a rash develops and the agent is absorbed through the skin. Large, fluid-filled blisters (similar to those caused by mustard gas exposure) develop after approximately 12 hours and cause pain for 2–3 days. These are severe chemical burns and begin with small blisters in the red areas of the skin within 2–3 hours and grow worse, encompassing the entire red area, for the ensuing 12–18 hours after initial exposure. Liquid lewisite has faster effects than lewisite vapor. Sufficient absorption can cause deadly liver necrosis.
Those exposed to lewisite can develop refractory hypotension (low blood pressure) known as Lewisite shock, with some features of arsenic toxicity. Lewisite damages capillaries, which then become leaky, reducing blood volume required to maintain blood pressure, a condition called hypovolemia. When the blood pressure is low, the kidneys may not receive enough oxygen and can be damaged.
Inhalation, the most common route of exposure, causes burning pain and irritation throughout the respiratory tract, nosebleed (epistaxis), laryngitis, sneezing, coughing, vomiting, difficult breathing (dyspnea), and in severe cases of exposure, can cause fatal pulmonary edema, pneumonitis, or respiratory failure. Ingestion results in severe pain, nausea, vomiting, and tissue damage. The results of eye exposure can range from stinging, burning pain and strong irritation to blistering and scarring of the cornea, along with blepharospasm, lacrimation, and edema of the eyelids and periorbital area. The eyes can swell shut, which can keep the eyes safe from further exposure. The most severe consequences of eye exposure to lewisite are globe perforation and blindness. Generalised symptoms also include restlessness, weakness, hypothermia and low blood pressure.
It is possible that Lewisite is carcinogenic: arsenic is categorized as a respiratory carcinogen by the International Agency for Research on Cancer, though it has not been confirmed that lewisite is a carcinogen.
Lewisite causes damage to the respiratory tract at levels lower than the odor detection threshold. Early tissue damage causes pain.
Treatment.
British anti-lewisite, also called dimercaprol, is the antidote for lewisite. It can be injected to prevent systemic toxicity, but will not prevent injury to the skin, eyes, or mucous membranes. Chemically, dimercaprol binds to the arsenic in lewisite. It is contraindicated in those with peanut allergies.
Other treatment for lewisite exposure is primarily supportive. First aid of lewisite exposure consists of decontamination and irrigation of any areas that have been exposed. Other measures can be used as necessary, such as airway management, assisted ventilation, and monitoring of vital signs. In an advanced care setting, supportive care can include fluid and electrolyte replacement. Because the tube may injure or perforate the esophagus, gastric lavage is contraindicated.
Long-term effects.
From one acute exposure, someone who has inhaled lewisite can develop chronic respiratory disease; eye exposure to lewisite can cause permanent visual impairment or blindness.
Chronic exposure to lewisite can cause arsenic poisoning (due to its arsenic content) and development of a lewisite allergy. It can also cause long-term illnesses or permanent damage to organs, depending on where the exposure has occurred, including conjunctivitis, aversion to light (photophobia), visual impairment, double vision (diplopia), tearing (lacrimation), dry mucous membranes, garlic breath, burning pain in the nose and mouth, toxic encephalopathy, peripheral neuropathy, seizures, nausea, vomiting, chronic obstructive pulmonary disease (COPD), bronchitis, dermatitis, skin ulcers, basal cell carcinoma, and squamous cell carcinoma.
Chemical composition.
Lewisite can be a mixture of molecules with a different number of vinylchloride groups on the arsenic chloride: lewisite itself (2-chlorovinylarsonous dichloride), along with "bis"(2-chlorovinyl)arsinous chloride (lewisite 2) and "tris"(2-chlorovinyl)arsine (lewisite 3). In addition, there are sometimes isomeric impurities: lewisite itself is mostly "trans"-2-chlorovinylarsonous dichloride, but the "cis" stereoisomer and the constitutional isomer (1-chlorovinylarsonous dichloride) may also be present.
Experimental and computational studies both find that the "trans"-2-chloro isomer is the most stable, and that the carbon–arsenic bond has a conformation in which the lone pair on the arsenic is approximately aligned with the vinyl group.
History.
Lewisite was synthesized in 1904 by Julius Arthur Nieuwland during studies for his PhD. In his thesis, he described a reaction between acetylene and arsenic trichloride, which led to the formation of lewisite. Exposure to the resulting compound made Nieuwland so ill he was hospitalized for several days.
Lewisite is named after the US chemist and soldier Winford Lee Lewis (1878–1943). In 1918, John Griffin, Julius Arthur Nieuwland's thesis advisor, drew Lewis's attention to Nieuwland's thesis at Maloney Hall, a chemical laboratory at The Catholic University of America, Washington D.C. Lewis then attempted to purify the compound through distillation but found that the mixture exploded on heating until it was washed with HCl.
Lewisite was developed into a secret weapon at a facility located in Cleveland, Ohio (The Cleveland Plant) at East 131st Street and Taft Avenue, and given the name "G-34", which had previously been the code for mustard gas, in order to confuse its development with mustard gas. On November 1, 1918, production began at a plant in Willoughby, Ohio.
It was not used in World War I, but Britain experimented with it in the 1920s as the "Dew of Death".
After World War I, the US became interested in lewisite because it was not flammable. Up until World War II, it had the military symbol of "M1", after which it was changed to "L". Field trials with lewisite during World War II demonstrated that casualty concentrations were not achievable under high humidity, due to the rate of hydrolysis and the characteristic odor of the chemical, and lacrymation forced troops to don masks and avoid contaminated areas. The United States produced about 20,000 tons of lewisite, keeping it on hand primarily as an antifreeze for mustard gas, or to penetrate protective clothing in special situations.
Lewisite was replaced by the mustard gas variant HT (a 60:40 mixture of sulfur mustard and O-Mustard), and was declared obsolete in the 1950s. Lewisite poisoning can be treated effectively with British anti-lewisite (dimercaprol). Most stockpiles of lewisite were neutralised with bleach and dumped into the Gulf of Mexico. Some remained at the Deseret Chemical Depot located outside Salt Lake City, Utah, but, as of January 18, 2012, all U.S stockpiles had been destroyed.
Producing or stockpiling lewisite was banned by the Chemical Weapons Convention. When the convention entered force in 1997, the parties declared world-wide stockpiles of 6,747 tonnes of lewisite. As of December 2015, 98% of the stockpiles had been destroyed.
In 2001, lewisite was found in a World War I weapons dump in Washington, D.C.
Controversy over Japanese deposits of lewisite in China.
In mid-2006, China and Japan were negotiating disposal of stocks of lewisite in northeastern China, left by Japanese military during World War II. People had died over the preceding twenty years from accidental exposure to these stockpiles.


Irina Mansurova

Irina Jafarovna Mansurova () (15 November 1925 – 6 April 1991) was a Tajikistani biochemist.
Born in Bukhara, Mansurova was a graduate of the Samarkand Medical Institute, from which she received her degree in 1948. From 1951 to 1959 she interned in the Department of Contagious Diseases at the Tajikistan State Medical Institute. In the latter year she became a Senior Scientific Worker, and until 1976 was director of the Biochemistry Division of Medical Research of the Tajik SSR. In 1967 she became a doctor of medicine, become a professor two years later. In 1976, she took over directorship of the biochemical laboratories of the Nature Preservation Division of the Tajikistan Academy of Sciences. In 1960 she was among those who participated in the foundation of the Department of Biochemistry at the Institute of Gastroenterology of the Academy of Sciences. She was the first Soviet scientist to discover principles governing the resolution of microchemical points on the liver; she also worked with the varied ferment constellations, and studied the effects of herbal medicine on organisms. She supervised the publication of the three-volume "Experimental Liver Pathology", and herself published such works as "The Biochemistry of the Liver During Hepatitis and Psoriasis of the Liver" (Dushanbe, 1964) and "Selected Lectures About Biochemistry" (Dushanbe, 1971); ultimately she published 240 papers during her career, including three monographs. Named a Distinguished Contributor to Health Services of the Soviet Union in 1967, she received a number of medals during her career. Mansurova was married to the therapist Hamid Mansurov; their daughter Farida became a noted biochemist in her own right, and later took over directorship of the Department of Biochemistry at the Institute of Gastroenterology.


Chlorophyllide

Chlorophyllide "a and Chlorophyllide "b are the biosynthetic precursors of chlorophyll "a" and chlorophyll "b" respectively. Their propionic acid groups are converted to phytyl esters by the enzyme chlorophyll synthase in the final step of the pathway. Thus the main interest in these chemical compounds has been in the study of chlorophyll biosynthesis in plants, algae and cyanobacteria. Chlorophyllide "a" is also an intermediate in the biosynthesis of bacteriochlorophylls.
Structures.
Chlorophyllide "a", is a carboxylic acid (R=H). In chlorophyllide "b", the methyl group at position 13 (IUPAC numbering for chlorophyllide "a") and highlighted in the green box, is replaced with a formyl group.
Biosynthesis steps up to formation of protoporphyrin IX.
In the early steps of the biosynthesis, which starts from glutamic acid, a tetrapyrrole is created by the enzymes deaminase and cosynthetase which transform aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate common to haem, sirohaem, cofactor F430, cobalamin and chlorophyll itself. The next intermediates are coproporphyrinogen III and protoporphyrinogen IX, which is oxidised to the fully aromatic protoporphyrin IX. Insertion of iron into protoporphyrin IX in for example mammals gives haem, the oxygen-carrying cofactor in blood, but plants combine magnesium instead to give, after further transformations, chlorophyll for photosynthesis.
Biosynthesis of chlorophyllides from protoporphyrin IX.
Details of the late stages of the biosynthetic pathway to chlorophyll differ in the plants (for example "Arabidopsis thaliana", "Nicotiana tabacum" and "Triticum aestivum") and bacteria (for example "Rubrivivax gelatinosus" and "Synechocystis") in which it has been studied. However, although the genes and enzymes vary, the chemical reactions involved are identical.
Insertion of magnesium.
Chlorophyll is characterised by having a magnesium ion coordinated within a ligand called a chlorin. The metal is inserted into protoporphyrin IX by the enzyme magnesium chelatase which catalyzes the reaction
Esterification of the ring C propionate group.
The next step towards the chlorophyllides is the formation of a methyl (CH3) ester on one of the propionate groups, which is catalysed by the enzyme Magnesium protoporphyrin IX methyltransferase in the methylation reaction
From porphyrin to chlorin.
The chlorin ring system features a five-membered carbon ring E is created when one of the propionate groups of the porphyrin is cyclised to the carbon atom linking the original pyrrole rings C and D. A series of chemical steps catalysed by the enzyme Magnesium-protoporphyrin IX monomethyl ester (oxidative) cyclase gives the overall reaction
In barley the electrons are provided by reduced ferredoxin, which can obtain them from photosystem I or, in the dark, from Ferredoxin—NADP(+) reductase: the cyclase protein is named XanL and is encoded by the "Xantha-l" gene. In anaerobic organisms such as "Rhodobacter sphaeroides" the same overall transformation occurs but the oxygen incorporated into magnesium-protoporphyrin IX 13-monomethyl ester comes from water in the reaction .
Reduction steps to chlorophyllide a.
Two further transformations are required to produce chlorophyllide "a". Both are reduction reactions: one converts a vinyl group to an ethyl group and the second adds two atoms of hydrogen to the pyrrole ring D, although the overall aromaticity of the macrocycle is retained.
These reactions proceed independently and in some organisms the sequence is reversed.
The enzyme divinyl chlorophyllide a 8-vinyl-reductase converts 3,8-divinylprotochlorophyllide to protochlorophyllide in reaction
This is followed by the reaction in which the pyrrole ring D is reduced by the enzyme protochlorophyllide reductase
This reaction is light-dependent but there is an alternative enzyme, , that uses reduced ferredoxin as its cofactor and is not dependent on light; it performs the a similar reaction but with the alternative substrate 3,8-divinylprotochlorophyllide
In the organisms which use this alternative sequence of reduction steps, the process is completed by the reaction catalysed by an enzyme which can take a variety of substrates and perform the required vinyl-group reduction, for example in this case
From chlorophyllide "a" to chlorophyllide "b".
Chlorophyllide "a" oxygenase is the enzyme that converts chlorophyllide "a" to chlorophyllide "b" by catalysing the overall reaction
Use in the biosynthesis of chlorophyll "a" and chlorophyll "b".
Chlorophyll synthase completes the biosynthesis of chlorophyll a by catalysing the reaction
This forms an ester of the carboxylic acid group in chlorophyllide "a" with the 20-carbon diterpene alcohol phytol.
Chlorophyll "b" is made by the same enzyme acting on chlorophyllide "b".
Use in the biosynthesis of bacteriochlorophylls.
Bacteriochlorophylls are the light harvesting pigments found in photosynthetic bacteria: they do not produce oxygen as a side-product. There are many such structures but all are biosynthetically related by being derived from chlorophyllide "a". Bacteriochlorophyll "a" is a typical example; its biosynthesis has been studied in "Rhodobacter capsulatus" and "Rhodobacter sphaeroides".
The first step is the reduction (with trans stereochemistry) of the pyrrole ring B, giving the characteristic 18-electron aromatic system of many bacteriochlorophylls. This is carried out by the enzyme chlorophyllide a reductase, which catalyses the reaction .
The next two steps convert the vinyl group first into a 1-hydroxyethyl group and then into the acetyl group of bacteriochlorophyllide "a". The reactions are catalysed by chlorophyllide a 31-hydratase () and bacteriochlorophyllide a dehydrogenase () as follows:
These three enzyme-catalysed reactions can occur in different sequences to produce bacteriochlorophyllide "a" ready for esterification to the final pigments for photosynthesis. The phytyl ester of bacteriochlorophyll "a" is not attached directly: rather, the initial intermediate is the ester with R=geranylgeranyl (from geranylgeranyl pyrophosphate) which is then subject to additional steps as three of the sidechain's alkene bonds are reduced.


Hepatitis C virus stem-loop VII

Hepatitis C virus stem-loop VII is a regulatory element found in the coding region of the RNA-dependent RNA polymerase gene, NS5B. Similarly to stem-loop IV, the stem-loop structure is important (but not essential) for colony formation, though its exact function and mechanism are unknown.


LGR6

Leucine-rich repeat-containing G-protein coupled receptor 6 is a protein that in humans is encoded by the "LGR6" gene. Along with the other G-protein coupled receptors LGR4 and LGR5, LGR6 is a Wnt signaling pathway mediator. "LGR6" also acts as an epithelial stem cell marker in squamous cell carcinoma in mice "in vivo."
This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants.


Magnetic drug delivery

Magnetic nanoparticle-based drug delivery is a means in which magnetic particles such as iron oxide nanoparticles are a component of a delivery vehicle for magnetic drug delivery, due to their easiness and simplicity with magnet-guidance. Magnetic nanoparticles can impart imaging and controlled release capabilities to drug delivery materials such as micelles, liposomes, and polymers.
Molecular magnets (single-molecule magnets) are a platform that incorporates insoluble (toxic) drugs into biocompatible carrier materials, without adding magnetic iron oxide nanoparticles, in which adversely affecting potential side effects attributed to iron overdose, as well as low drug loading efficiency. The drawbacks in conventional magnetic drug delivery methods can be overcame by switching from typical iron oxide nanoparticles to ones based on molecular magnet, such as Fe(salen)-based "anticancer nanomagnet" with proven cancer-fighting ability. However, insoluble drugs including Fe(salen) also have some inherent drawbacks, such as poor water solubility, loss of magnetic activity in solvents, and potential cytotoxicity when accumulated in tissues and organs. As an alternative synthetic method of magnetic drug delivery, a "non-iron oxide"-based smart delivery platform has been very recently developed by self-assembly of the Fe(salen) drugs into nano-cargoes encapsulated by a smart polymer, exhibiting bio-safe multifunctional magnetic capabilities, including MRI, magnetic field- and pH-responsive heat-releasing hyperthermia effects, and controlled release.


Coelenteramine

Coelenteramine is a metabolic product of the bioluminescent reactions in organisms that utilize coelenterazine. It was first isolated from "Aequorea victoria" along with coelenteramide after coelenterates were stimulated to emit light.


Militia (film)

Militia is a 2000 American direct-to-video action film directed by Jim Wynorski. It stars Dean Cain, Jennifer Beals and Frederic Forrest. The film features scenes taken straight from "" spliced into newly filmed scenes to make up its action sequences.
Plot.
A raid, led by Ethan Carter is carried out by ATF agents against a militia group, the Brotherhood of Liberty. Their leader, William Fain, is captured and his family is mistakenly killed in the raid. Two years later, other persons from the same militia group break into a chemicals corporation called Cyberdyne Systems and steal anthrax. Their plan is to use this anthrax to engineer a full-blown attack against the US government. Ethan must now use the imprisoned William to infiltrate the Brotherhood of Liberty and stop the attack against the government.


Quercetin 2,3-dioxygenase

In enzymology, a quercetin 2,3-dioxygenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are quercetin and O2, whereas its 3 products are 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, CO, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on single donors with O2 as oxidant and incorporation of two atoms of oxygen into the substrate (oxygenases). The oxygen incorporated need not be derived from O2. The systematic name of this enzyme class is quercetin:oxygen 2,3-oxidoreductase (decyclizing). Other names in common use include quercetinase, and flavonol 2,4-oxygenase. It has 2 cofactors: iron, and Copper.
Structural studies.
As of late 2007, 6 crystal structures have been solved for this class of enzymes, with PDB accession codes , , , , , and .


Melanin-concentrating hormone receptor

Two Melanin-concentrating hormone receptors (MCHR) have recently been characterized: MCH-R1 and MCH-R2. These two receptors share approximately 38% homology.
Clinical significance.
Antagonists might be useful in the treatment of obesity and anxiety and depression. An agonist might have possible utility as a treatment for osteoporosis and insomnia
Research is ongoing for antagonists affecting MCH receptors R1 and R2.


Fluorescence-activating and absorption-shifting tag

FAST ("Fluorescence-Activating and absorption-Shifting Tag") is a small, genetically-encoded, protein tag which allows for fluorescence reporting of proteins of interest. Unlike natural fluorescent proteins and derivates such as GFP or mCherry, FAST is not fluorescent by itself. It can bind selectively a fluorogenic chromophore derived from 4-hydroxybenzylidene rhodanine (HBR), which is itself non fluorescent unless bound. Once bound, the pair of molecules goes through a unique fluorogen activation mechanism based on two spectroscopic changes, increase of fluorescence quantum yield and absorption red shift, hence providing high labeling selectivity. The FAST-fluorogen reporting system can be used in fluorescence microscopy, flow cytometry and any other fluorometric method to explore the living world: biosensors, protein trafficking.
FAST, a small 14 kDa protein, was engineered from the photoactive yellow protein (PYP) by directed evolution. It was reported for the first time in 2016 by researchers from Ecole normale supérieure de Paris.
Mechanism.
FAST pertains to a chemical-genetic strategy for specific labeling of proteins. A peptide domain, called "tag", is genetically encoded to be bound to a protein of interest (by combination of their respective genes by means of transfection or infection). This tag is the anchor for a synthetic fluorescent probe to be further added. Such chemical-genetic approach was already implemented besides natural fluorescent proteins such as GFP or their derivatives such as mCherry in several systems already widely used:
Several versions of FAST have been described differing by a small number of mutations, "e.g.", FAST1 (a.k.a. Y-FAST), FAST2 (a.k.a. iFAST), or a dimer, td-FAST. Also, a complementation split version for monitoring protein-protein interactions was developed, splitFAST. A number of plasmids displaying FAST or splitFAST genes are available at Addgene.
Applications.
The FAST-fluorogen reporting system is used in fluorescence microscopy, flow cytometry and any other fluorometric methods to explore the living world, including biosensors and protein trafficking. FAST has been reported for dynamic imaging of biofilms because of its unique capacity of fluorescence in low-oxygen conditions. For the same reason it allows for imaging and FACSing anaerobes, such as "Clostridium", used for biomass fermentation like the ABE fermentation. FAST has also been reported for super-resolution microscopy of living cells.
A number of fluorogens were developed for FAST and its derivates by The Twinkle Factory, varying by their emission wavelength, their brightness and their tag affinity. Some are non permeant, "i.e.", they can't go through cell membranes, hence specifically labeling membrane proteins or extracellular proteins, allowing for, "e.g.", monitoring trafficking from synthesis until excretion.


Glycine riboswitch

The bacterial glycine riboswitch is an RNA element that can bind the amino acid glycine. Glycine riboswitches usually consist of two metabolite-binding aptamer domains with similar structures in tandem. The aptamers were originally thought to cooperatively bind glycine to regulate the expression of downstream genes. In "Bacillus subtilis", this riboswitch is found upstream of the "gcvT" operon which controls glycine degradation. It is thought that when glycine is in excess it will bind to both aptamers to activate these genes and facilitate glycine degradation.
The originally discovered, truncated version of the glycine riboswitch exhibits sigmoidal binding curves with Hill coefficients greater than one, which led to the idea of positive cooperativity between the two aptamer domains. Data in 2012 shows that cooperative binding does not occur in the switch with its extended 5' leader, though the purpose of the switch's dual aptamers is still uncertain.
Atomic resolution structures of portions of glycine riboswitches have been obtained by X-ray crystallography.
"In vivo" experiments demonstrated that glycine does not need to bind both aptamers for regulation. Mutation to the first aptamer caused greatest reduction in downstream gene expression, while mutation to the second one had varying effects. Glycine-induced expression of the "gcvT" operon is needed for "B. subtilise" growth, swarming motility and biofilm formation (in high glycine environment).


Aganodine

Aganodine is a guanidine that activates presynaptic imidazoline receptors. Through its agonism at imidazoline receptors, aganodine inhibits the presynaptic release of norepinephrine.