Joe L. Franklin

Joseph Louis Franklin (1906 – August 25, 1982) was a Robert A. Welch Professor of Chemistry at Rice University known for his research in mass spectrometry and ion molecule chemistry. The "Frank H. Field and Joe L. Franklin Award for Outstanding Achievement in Mass Spectrometry" is named after him and Frank H. Field.
Early life and education.
Joseph Franklin was born in Natchez, Mississippi in 1906 but his family moved to Texas early in his life. He went to the University of Texas to study chemistry and received a B.S. degree in 1929, M.S. in 1930, and Ph.D. in 1934.
Humble Oil.
Franklin took a position at Humble Oil in Baytown, Texas in 1934 where he established a mass spectrometry research group. He recruited Frank Field to Humble Oil in 1952 and they co-wrote "Electron Impact Phenomena and the Properties of Gaseous Ions" in 1957. Franklin took a two year leave 1957-1958 at the National Bureau of Standards in Washington, D.C. before returning to Humble.
Rice University.
In 1963, Franklin took a position as Robert A. Welch Professor of chemistry at Rice University. He became an emeritus professor in 1976. He helped to found the American Society for Mass Spectrometry and became the first president of that organization in 1969.
Field and Franklin Award.
In 1983, the "Frank H. Field and Joe L. Franklin Award for Outstanding Achievement in Mass Spectrometry" was established in his honor by the American Chemical Society.


Para-Fluorophenylpiperazine

"para"-Fluorophenylpiperazine (pFPP, 4-FPP, 4-Fluorophenylpiperazine; Fluoperazine, Flipiperazine) is a piperazine derivative with mildly psychedelic and euphoriant effects. It has been sold as an ingredient in legal recreational drugs known as "Party pills", initially in New Zealand and subsequently in other countries around the world.
pFPP has been found "in vitro" to act mainly as a 5-HT1A receptor agonist, with some additional affinity for the 5-HT2A and 5-HT2C receptors. It has also been shown to inhibit the reuptake of serotonin and norepinephrine, and to possibly induce their release.
pFPP was originally discovered as a metabolite of the hypnotic 5-HT2A and α1-adrenergic receptor antagonist niaprazine in 1982, but was rediscovered in 2003 as a potential recreational drug, and sold as an ingredient in "Party pills" in New Zealand, under brand names such as "The Big Grin", "Mashed", and "Extreme Beans". Subsequently it has continued to be used as an ingredient in black market "ecstasy" pills around the world.
pFPP has little stimulant effects, with its subjective effects derived mainly from its action as a 5-HT1A receptor agonist. pFPP is active at doses between 20 and 150 mg, but higher doses cause a range of side-effects such as migraine headaches, muscle aches, anxiety, nausea, and vomiting. Metabolic studies have shown pFPP to be an inhibitor of various Cytochrome P450 enzymes in the liver which may contribute to its side-effect profile.
Based on the recommendation of the EACD, the New Zealand government has passed legislation which placed BZP, along with a number of other piperazine derivatives, into Class C of the New Zealand Misuse of Drugs Act 1975. A ban was intended to come into effect in New Zealand on December 18, 2007, but the law change did not go through until the following year, and the sale of BZP and the other listed piperazines became illegal in New Zealand as of 1 April 2008. An amnesty for possession and usage of these drugs remained until October 2008, at which point they became completely illegal. This drug has been detected in a drug-facilitated sexual assault case in the United States of America.


Nallin Farm House

The Nallin Farm House and the related Nallin Farm Springhouse and Bank Barn are located on Fort Detrick at Frederick, Maryland.
The Federal style brick farmhouse was built in stages between the 1780s and the 1830s and serves as the residence of the Fort Detrick commanding officer. It is known on post as "Building 1652".
The Nallin Farm was incorporated into Fort Detrick upon the post's expansion in 1955. It was added to the National Register of Historic Places on May 23, 1974.


Pterygium

Pterygium refers to any winglike triangular membrane occurring in the neck, eyes, knees, elbows, ankles or digits.
The term comes from the Greek word "pterygion" meaning "wing".
Types.
A pterygium grows in response to exposure to ultraviolet light. They are more common in light-skinned people living nearer the equator, particularly where outdoor activities are popular.
As the pterygium grows, it replaces the corneal epithelium, and erodes the superficial layers beneath it. These layers are Bowman's membrane, and the anterior corneal stromal lamellae. The pterygium pulls and distorts the cornea as it enlarges.
Effects.
A pterygium reduces the vision in several ways:
Surgical removal.
Indications for surgery, in order of decreasing importance:
Surgery is usually performed under local anaesthetic with light sedation as day surgery. The pterygium is stripped carefully off the surface of the eye. If this is all that is done, the pterygium regrows frequently. The technique with the lowest recurrence rate uses an auto graft of conjunctiva from under the eyelid. This is placed over the defect remaining from the removed pterygium. The graft can be stitched in place, which is time consuming, and painful for the patient afterwards.
An alternative is the use of tissue adhesive fibrin glue (Tisseel or Full Link or Beriplast P or Quixil). A Cochrane Review including 14 studies and last updated October 2016, found that using fibrin glue when doing conjunctival autografting was associated with a reduced likelihood of the pterygium recurring compared with sutures. The review found that operations may take less time but fibrin glue may be associated with more complications (for example, rupture, shrinking and inflammation (granuloma). A 3-year clinical study on the application of ologen collagen matrix as excision site grafts showed significantly improved surgery success rates.
The mechanism of the collagen matrix graft (commercially available as ologen®) works by promoting healthy cell growth into the matrix, thus preventing conjunctiva overgrowth that can cover the iris.
Natural history.
A pterygium grows very slowly. Usually it takes several years or decades to progress.


Sequencing

In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succinctly summarizes much of the atomic-level structure of the sequenced molecule.
DNA sequencing.
DNA sequencing is the process of determining the nucleotide order of a given DNA fragment. So far, most DNA sequencing has been performed using the chain termination method developed by Frederick Sanger. This technique uses sequence-specific termination of a DNA synthesis reaction using modified nucleotide substrates. However, new sequencing technologies such as pyrosequencing are gaining an increasing share of the sequencing market. More genome data are now being produced by pyrosequencing than Sanger DNA sequencing. Pyrosequencing has enabled rapid genome sequencing. Bacterial genomes can be sequenced in a single run with several times coverage with this technique. This technique was also used to sequence the genome of James Watson recently.
The sequence of DNA encodes the necessary information for living things to survive and reproduce. Determining the sequence is therefore useful in fundamental research into why and how organisms live, as well as in applied subjects. Because of the key importance DNA has to living things, knowledge of DNA sequences is useful in practically any area of biological research. For example, in medicine it can be used to identify, diagnose, and potentially develop treatments for genetic diseases. Similarly, research into pathogens may lead to treatments for contagious diseases. Biotechnology is a burgeoning discipline, with the potential for many useful products and services.
The Carlson curve is a term coined by "The Economist" to describe the biotechnological equivalent of Moore's law, and is named after author Rob Carlson. Carlson accurately predicted the doubling time of DNA sequencing technologies (measured by cost and performance) would be at least as fast as Moore's law. Carlson curves illustrate the rapid (in some cases hyperexponential) decreases in cost, and increases in performance, of a variety of technologies, including DNA sequencing, DNA synthesis, and a range of physical and computational tools used in protein expression and in determining protein structures.
Sanger sequencing.
In chain terminator sequencing (Sanger sequencing), extension is initiated at a specific site on the template DNA by using a short oligonucleotide 'primer' complementary to the template at that region. The oligonucleotide primer is extended using a DNA polymerase, an enzyme that replicates DNA. Included with the primer and DNA polymerase are the four deoxynucleotide bases (DNA building blocks), along with a low concentration of a chain terminating nucleotide (most commonly a di-deoxynucleotide). The deoxynucleotides lack in the OH group both at the 2' and at the 3' position of the ribose molecule, therefore once they are inserted within a DNA molecule they prevent it from being further elongated. In this sequencer four different vessels are employed, each containing only of the four dideoxyribonucleotides; the incorporation of the chain terminating nucleotides by the DNA polymerase in a random position results in a series of related DNA fragments, of different sizes, that terminate with a given dideoxiribonucleotide. The fragments are then size-separated by electrophoresis in a slab polyacrylamide gel, or more commonly now, in a narrow glass tube (capillary) filled with a viscous polymer.
An alternative to the labelling of the primer is to label the terminators instead, commonly called 'dye terminator sequencing'. The major advantage of this approach is the complete sequencing set can be performed in a single reaction, rather than the four needed with the labeled-primer approach. This is accomplished by labelling each of the dideoxynucleotide chain-terminators with a separate fluorescent dye, which fluoresces at a different wavelength. This method is easier and quicker than the dye primer approach, but may produce more uneven data peaks (different heights), due to a template dependent difference in the incorporation of the large dye chain-terminators. This problem has been significantly reduced with the introduction of new enzymes and dyes that minimize incorporation variability.
This method is now used for the vast majority of sequencing reactions as it is both simpler and cheaper. The major reason for this is that the primers do not have to be separately labelled (which can be a significant expense for a single-use custom primer), although this is less of a concern with frequently used 'universal' primers. This is changing rapidly due to the increasing cost-effectiveness of second- and third-generation systems from Illumina, 454, ABI, Helicos, and Dover.
Pyrosequencing.
The pyrosequencing method is based on the detection of the pyrophosphate release on nucleotide incorporation. Before performing pyrosequencing, the DNA strand to sequence has to be amplified by PCR. Then the order in which the nucleotides have to be added in the sequencer is chosen (i.e. G-A-T-C). When a specific nucleotide is added, if the DNA polymerase incorporates it in the growing chain, the pyrophosphate is released and converted into ATP by ATP sulfurylase. ATP powers the oxidation of luciferase through the luciferase; this reaction generates a light signal recorded as a pyrogram peak. In this way, the nucleotide incorporation is correlated to a signal. The light signal is proportional to the amount of nucleotides incorporated during the synthesis of the DNA strand (i.e. two nucleotides incorporated correspond to two pyrogram peaks). When the added nucleotides aren't incorporated in the DNA molecule, no signal is recorded; the enzyme apyrase removes any unincorporated nucleotide remaining in the reaction.
This method requires neither fluorescently-labelled nucleotides nor gel electrophoresis.
Pyrosequencing, which was developed by Pål Nyrén and Mostafa Ronaghi DNA, has been commercialized by Biotage (for low-throughput sequencing) and 454 Life Sciences (for high-throughput sequencing). The latter platform sequences roughly 100 megabases [now up to 400 megabases] in a seven-hour run with a single machine. In the array-based method (commercialized by 454 Life Sciences), single-stranded DNA is annealed to beads and amplified via EmPCR. These DNA-bound beads are then placed into lls on a fiber-optic chip along with enzymes which produce light in the presence of ATP. When free nucleotides are washed over this chip, light is produced as ATP is generated when nucleotides join with their complementary base pairs. Addition of one (or more) nucleotide(s) results in a reaction that generates a light signal that is recorded by the CCD camera in the instrument. The signal strength is proportional to the number of nucleotides, for example, homopolymer stretches, incorporated in a single nucleotide flow.
Large-scale sequencing.
Whereas the methods above describe various sequencing methods, separate related terms are used when a large portion of a genome is sequenced. Several platforms were developed to perform exome sequencing (a subset of all DNA across all chromosomes that encode genes) or whole genome sequencing (sequencing of the all nuclear DNA of a human).
RNA sequencing.
RNA is less stable in the cell, and also more prone to nuclease attack experimentally. As RNA is generated by transcription from DNA, the information is already present in the cell's DNA. However, it is sometimes desirable to sequence RNA molecules. While sequencing DNA gives a genetic profile of an organism, sequencing RNA reflects only the sequences that are actively expressed in the cells. To sequence RNA, the usual method is first to reverse transcribe the RNA extracted from the sample to generate cDNA fragments. This can then be sequenced as described above.
The bulk of RNA expressed in cells are ribosomal RNAs or small RNAs, detrimental for cellular translation, but often not the focus of a study. This fraction can be removed "in vitro", however, to enrich for the messenger RNA, also included, that usually is of interest. Derived from the exons these mRNAs are to be later translated to proteins that support particular cellular functions. The expression profile therefore indicates cellular activity, particularly desired in the studies of diseases, cellular behaviour, responses to reagents or stimuli. Eukaryotic RNA molecules are not necessarily co-linear with their DNA template, as introns are excised. This gives a certain complexity to map the read sequences back to the genome and thereby identify their origin.
For more information on the capabilities of next-generation sequencing applied to whole transcriptomes see: RNA-Seq and MicroRNA Sequencing.
Protein sequencing.
Methods for performing protein sequencing
include:
If the gene encoding the protein is known, it is currently much easier to sequence the DNA and infer the protein sequence. Determining part of a protein's amino-acid sequence (often one end) by one of the above methods may be sufficient to identify a clone carrying this gene.
Polysaccharide sequencing.
Though polysaccharides are also biopolymers, it is not so common to talk of 'sequencing' a polysaccharide, for several reasons. Although many polysaccharides are linear, many have branches. Many different units (individual monosaccharides) can be used, and bonded in different ways. However, the main theoretical reason is that whereas the other polymers listed here are primarily generated in a 'template-dependent' manner by one processive enzyme, each individual join in a polysaccharide may be formed by a different enzyme. In many cases the assembly is not uniquely specified; depending on which enzyme acts, one of several different units may be incorporated. This can lead to a family of similar molecules being formed. This is particularly true for plant polysaccharides. Methods for the structure determination of oligosaccharides and polysaccharides include NMR spectroscopy and methylation analysis.


Enumeral

Enumeral was a Cambridge, Massachusetts-based biotechnology company which developed monoclonal antibody immunotherapies through an 'immunoprofiling' platform that allowed it to scan the human immune microenvironment and identify and validate potential drug candidates. The company filed for Chapter 11 bankruptcy and arranged to sell its assets to Xoma Corporation in January 2018.
The company.
Enumeral was founded in 2009 to bring together various immunoprofiling technologies from Harvard University, Massachusetts Institute of Technology, the Whitehead Institute for Biomedical Research and Massachusetts General Hospital. The company's Scientific Founder was Christopher Love, Associate Professor of Chemical Engineering at MIT; the Executive Chairman is John Rydzewskand and its CEO is Arthur Tinkelenberg. In 2014 the company was taken public through a reverse takeover into a shell called Cerulean Group. Its stock is traded OTC in the US, with trading in the OTCQB marketplace tier commencing on 4 August 2014. The stock code is ENUM.
By 2015, Enumeral had completed pre-clinical development of PD-1 inhibitors and sought partners to enter clinical development with. In December 2016, Enumeral completed raising to fund long-term development plans, but by May 2017, the company announced it only had sufficient cash on hand to fund operations through June 2017. Shortly thereafter, in June, the company dismissed its R&D research staff. In August 2017, Enumeral was kicked out of its headquarters in Cambridge due to non-payment of rent and other fees. The Cambridge headquarters was also the home of Celgene and Unum Therapeutics. By the time the company lost its headquarters, Arthur Tinkelenberg was being described as the company's "former president and chief executive officer". In January 2018, Enumeral struck a deal with Xoma Corporation, located in the San Francisco Bay Area, to sell its assets for , while concurrently filing for Chapter 11 bankruptcy.
Platform.
Enumeral's platform consists of various proprietary cellular libraries derived from target-specific immunized sources or from human patient donors. The platform has three main parts:
Anti PD-1 antibodies.
An early commercial interest of Enumeral has focused on PD-1, currently targeted by two FDA-approved monoclonal antibody drugs - Keytruda, from Merck & Co., and Opdivo, from Bristol-Myers Squibb. In 2015 Enumeral reported that it had used its platform to raise anti-PD-1 antibodies that did not compete with Keytruda or Opdivo for binding to PD-1, nor did they appear to compete with PD-1's ligand, PD-L1. These potentially allosteric antibodies also produced more interferon gamma and showed dose-dependent increases in T cell CD25 expression. Further, Enumeral's antibodies caused higher T cell activation in "ex vivo" human assays than the currently marketed anti-PD-1 antibodies and, in that same setting, in combination with one of the marketed antibodies, could elicit an additive effect on T cell activation. Enumeral expects to take an anti-PD-1 antibody into clinical testing in 2016.
Merck collaboration.
In December 2014 Enumeral announced a collaboration with Merck & Co. in which the two companies would use the Enumeral platform to interrogate the tumor microenvironment in colorectal cancer tissues obtained directly from patients, with the aim of identifying functional cellular responses to Merck-developed immuno-oncology products. In September 2015 Enumeral announced that the Merck collaboration had achieved its first milestone, enabling Enumeral to receive a milestone payment from Merck.


Hyponitrite reductase

In enzymology, a hyponitrite reductase is an enzyme that catalyzes the oxidation of hydroxylamine by the nicotinamide adenine dinucleotide cation (NAD+) into hyponitrous acid HON=NOH:
This systematic name of this enzyme class hydroxylamine:NAD+ oxidoreductase. It is also called NADH2:hyponitrite oxidoreductase.
This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with NAD+ or NADP+ as acceptor. It employs one cofactor, metal.


GRID2

Glutamate receptor, ionotropic, delta 2, also known as GluD2, GluRδ2, or δ2, is a protein that in humans is encoded by the "GRID2" gene. This protein together with GluD1 belongs to the delta receptor subtype of ionotropic glutamate receptors. They possess 14–24% sequence homology with AMPA, kainate, and NMDA subunits, but, despite their name, do not actually bind glutamate or various other glutamate agonists.
delta iGluRs have long been considered orphan receptors as their endogenous ligand was unknown. They are now believed to bind glycine and D-serine but these do not result in channel opening.
Function.
GluD2-containing receptors are selectively/predominantly expressed in Purkinje cells in the cerebellum where they play a key role in synaptogenesis, synaptic plasticity, and motor coordination.
GluD2 induces synaptogenesis through interaction of its N-terminal domain with Cbln1, which in turn interacts with presynaptic neurexins, forming a bridge across cerebellar synapses.
The main functions of GluD2 in synaptic plasticity are carried out by its intracellular C-terminus. This is regulated by D-serine, which binds to the ligand-binding domain and results in changes in the structure of GluD2 without opening the channel. These changes may signal up to the N-terminal domain or down to the C-terminal domain to alter protein-protein interactions.
Pathology.
A heterozygous deletion in GRID2 in humans causes a complicated spastic paraplegia with ataxia, frontotemporal dementia, and lower motor neuron involvement whereas a homozygous biallelic deletion leads to a syndrome of cerebellar ataxia with marked developmental delay, pyramidal tract involvement and tonic upgaze, that can be classified as an ataxia with oculomotor apraxia (AOA) and has been named spinocerebellar ataxia, autosomal recessive type 18 (SCAR18).
A gain of channel function, resulting from a point mutation in mouse GRID2, is associated with the phenotype named 'lurcher', which in the heterozygous state leads to ataxia and motor coordination deficits resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis.
Ligands.
9-Aminoacridine, 9-tetrahydroaminoacridine, N1-dansyl-spermine, N1-dansyl-spermidine, and pentamidine have been shown to act as antagonists of δ2-containing receptors.
Interactions.
GRID2 has been shown to interact with GOPC, GRIK2, PTPN4 and GRIA1. A possible correlation between GRID2 and the pre-B lymphocyte protein 3 (VPREB3) has been suggested, due to the apparent importance of B-lymphocytes in the origins of cerebellar Purkinje neurons in humans. Morphological studies conducted in GRID2-knockout mice suggest that GRID2 may be present in lymphocytes as well as in the adrenal cortex, however further studies must be conducted to confirm these claims.


4,5-MDO-DMT

4,5-MDO-DMT, or 4,5-methylenedioxy-"N","N"-dimethyltryptamine, is a lesser-known psychedelic drug. It is the 4,5-methylenedioxy analog of DMT. 4,5-MDO-DMT was first synthesized by Alexander Shulgin, though in his book "TiHKAL" it was not tested to determine its psychoactive effects. 4,5-MDO-DMT has been the subject of limited subsequent testing; with behavioral disruption studies performed in male rats indicating that its hallucinogenic potency is less than that of 4,5-MDO-DiPT but greater than that of 5,6-MDO-DiPT.


Lipotropic

Lipotropic compounds are those that help catalyse the breakdown of fat during metabolism in the body.
Choline is the major lipotrope in mammals and other known lipotropes are important only insofar as they contribute to the synthesis of choline.
A lipotropic nutrient promotes or encourages the export of fat from the liver. Lipotropics are necessary for maintenance of a healthy liver, and for burning the exported fat for additional energy. Without lipotropics, such as choline and inositol, fats and bile can become trapped in the liver, causing severe problems such as cirrhosis and blocking fat metabolism. Choline is essential for fat metabolism. Choline functions as a methyl donor and it is required for proper liver function. Like inositol, choline is a lipotropic. Inositol exerts lipotropic effects as well. An "unofficial" member of the B vitamins, inositol has even been shown to relieve depression and panic attacks.
Methionine, an essential amino acid, is a major lipotropic compound in humans. When estrogen levels are high, the body requires more methionine. Estrogens reduce bile flow through the liver and increase bile cholesterol levels. Methionine helps deactivate estrogens.
Methionine levels also affect the amount of sulfur-containing compounds, such as glutathione, in the liver. Glutathione and other sulfur-containing peptides (small proteins) play a critical role in defending against toxic compounds. When higher levels of toxic compounds are present, more methionine is needed.
Choline assists detoxification reactions in the liver. Though choline can be synthesized from methionine or serine, recent evidence indicates that choline is an essential nutrient.
Betaine hydrochloride is a powerful lipotropic and increases gastric acid. Betaine itself (in a non-hydrochloric form, also known as TMG or Trimethylglycine) also has a lipotropic effect.
Oxibetaine is another agent listed as a lipotropic compound.


Brenda Ryman

Brenda Edith Ryman (6 December 1922 – 20 November 1983) was a biochemist and Mistress of Girton College, Cambridge.
Ryman was educated at Colston's Girls' School and Girton College, Cambridge. She was on the staff of the Royal Free Hospital from 1948 to 1972; Professor of Biochemistry at Charing Cross Hospital from 1972; and Mistress of Girton College, Cambridge from 1976 until her death.


John M. Olson

John M. Olson (September 18, 1929 – July 2, 2017) was an American biophysicist and pioneer researcher in photosynthesis, especially light harvesting complex of green sulfur bacteria.
In 1962 Olson was the first to discover and characterize pigment-protein complex of green sulfur bacteria (Chlorobi), which was later named after him as Fenna–Matthews–Olson complex. In 1980s he intensively studied bacteriochlorophyll self-assembly in chlorosomes of green sulfur and green non-sulfur bacteria.


Marianne Grunberg-Manago

Marianne Grunberg-Manago (January 6, 1921 – January 3, 2013) was a Soviet-born French biochemist. Her work helped make possible key discoveries about the nature of the genetic code.
Early life.
Grunberg-Manago was born into a family of artists who adhered to the teachings of the Swiss educational reformer Johann Pestalozzi. When she was 9 months old, Grunberg-Manago's parents emigrated from the Soviet Union to France.
Education and Research.
Grunberg-Manago studied biochemistry and, in 1955, while working in the lab of Spanish-America biochemist Severo Ochoa, she discovered the first nucleic-acid-synthesizing enzyme. Initially, everyone thought the new enzyme was an RNA polymerase used by "E. coli" cells to make long chains of RNA from separate nucleotides. But although the new enzyme could link a few nucleotides together, the reaction was highly reversible and it later became clear that the enzyme, polynucleotide phosphorylase, usually catalyzes the "breakdown" of RNA, not its synthesis.
Nonetheless, the enzyme was extraordinarily useful and important. Almost immediately, Marshall Nirenberg and J. Heinrich Matthaei put it to use to form the first three-nucleotide RNA codons, which coded for the amino acid phenylalanine. This first step in cracking the genetic code entirely depended on the availability of Grunberg-Manago’s enzyme.
In 1959, Ochoa and Arthur Kornberg won the 1959 Nobel Prize in Physiology or Medicine "for the synthesis of the nucleic acids RNA and DNA." She was elected a Foreign Honorary Member of the American Academy of Arts and Sciences in 1978 and a Foreign Associate Member of the National Academy of Sciences in 1982.
Grunberg-Manago was the first woman to direct the International Union of Biochemistry, and she was also the first woman to preside the French Academy of Sciences from 1995 to 1996.
Later life and death.
Late in her career, Grunberg-Manago was named emeritus director of research at CNRS, France’s National Center for Scientific Research.
Grunberg-Manago died in January, 2013, three days before her 92nd birthday.


2-Methyl-5-hydroxytryptamine

2-Methyl-5-hydroxytryptamine (2-Methylserotonin, 2-Methyl-5-HT) is a tryptamine derivative closely related to the neurotransmitter serotonin which acts as a moderately selective full agonist at the 5-HT3 receptor.


Laccaria bicolor

Laccaria bicolor is a small tan-colored mushroom with lilac gills. It is edible but not choice, and grows in mixed birch and pine woods. It is found in the temperate zones of the globe, in late summer and autumn. "L. bicolor" is an ectomycorrhizal fungus used as a soil inoculant in agriculture and horticulture.
Taxonomy.
It was initially described as a subspecies of "Laccaria laccata" by French mycologist René Maire in 1937, before being raised to species rank by P.D. Orton in 1960. Like others in its genus it has the common name of 'Deceiver', because of its propensity to fade and become hard to identify.
Description.
The cap is across, convex to flat, and with a central navel. It is often incurved at the margin, and is various shades of ochraceous-buff, and tan, depending on moisture content. The fibrillose stipe is the same color, and with a distinct lilac down towards the base. The flesh is whitish, tinged with pink, or ochraceous, and has no apparent distinctive smell, or taste. The gills are pale lilac at first, fading paler. The spores are white. The picture on the right shows young specimens with quite vivid coloration. More often, they are found duller in appearance.
Distribution and habitat.
This species is mycorrhizal with a range of trees, and is found throughout the temperate zones of the world, in summer and autumn. This includes temperate and boreal forests of North America and probably Northern Europe. It seems to prefer birch and pine woods.
Carnivory.
"Laccaria bicolor" is one of a number of species of carnivorous fungi, but one of the few that catches and kills arthropods, specifically springtails.
Ectomycorrhizae.
This species forms ectomycorrhizal associations with a wide variety of tree species, such as red pine, jack pine, and black spruce. Studies have shown that "L. bicolor" is more effective in early colonization of pine roots compared to other ectomycorrhiza forming fungi. In field studies, it preferentially colonizes and improves the survival of red pine. Actinobacteria isolates, e.g. from the genus "Streptomyces", obtained from old growth Norway spruce field sites have been shown to stimulate the growth of "Laccaria bicolor" in the laboratory.
Genome.
"Laccaria bicolor" was the first ectomycorrhizal fungus to have its genome sequenced. The genome is 65 megabases long and is estimated to contain 20,000 protein coding genes. Analysis revealed a large number of small secreted proteins of unknown function, several of which are only expressed in symbiotic tissues, where they probably play a role in initiating symbiosis. It lacks enzymes that are able to degrade plant cell walls but does possess enzymes which can degrade other polysaccharides, revealing how it is able to grow both in soil and in association with plants.


Chrysemys picta


Bacillus subtilis type I antitoxin SR6

SR6 is a 100 nucleotide long antisense RNA antitoxin that overlaps 2 toxins: 3' end of "yonT" and "yoyJ" at its 5'end. In type I toxin-antitoxin (TA) systems the antitoxin is a small RNA that neutralizes a toxin protein. Several type I TA systems have been described in "B. subtilis". "YonT"/SR6 system is located on the SPβ prophage of the "B. subtilis" chromosome and it was shown to be multi-stress responsive. SR6 acts by promoting "yonT" mRNA degradation. It may regulate the second toxin, "yoyJ" by a different mechanism.


Operation Big Itch

Operation Big Itch was a U.S. entomological warfare field test using uninfected fleas to determine their coverage and survivability as a vector for biological agents. The tests were conducted at Dugway Proving Ground in 1954.
Operation.
Operation Big Itch was a September 1954 series of tests at Dugway Proving Ground in Utah. The tests were designed to determine coverage patterns and survivability of the tropical rat flea ("Xenopsylla cheopis") for use in biological warfare as disease vector. The fleas used in these trials were not infected by any biological agent. The fleas were loaded into two types of munitions and dropped from the air. The E14 bomb and E23 bomb, which could be clustered into the E86 cluster bomb and E77 bomb, respectively. When the cluster bombs reached 2,000 or 1,000 feet (600 or 300 m) the bomblets would drop via parachute, disseminating their vector.
The E14 was designed to hold 100,000 fleas and the E23 was designed to hold 200,000 fleas but the E23 failed in over half of the preliminary Big Itch tests. E23s malfunctioned during testing and the fleas were released into the aircraft where they bit the pilot, bombardier and an observer. As a result, the remaining Big Itch tests were conducted using only the smaller capacity E14. Guinea pigs were used as test subjects and placed around a circular grid.
Results.
Big Itch proved successful, the tests showed that not only could the fleas survive the drop from an airplane but they also soon attached themselves to hosts. The weapon proved able to cover a battalion-sized target area and disrupt operations for up to one day. The one-day limit was due to the activity of the fleas; the air dropped fleas were only active for about 24 hours.


Kuznechik (camel)

Kuznechik (, meaning "grasshopper") was a Bactrian camel that became known for following the Soviet Red Army in its advance towards Germany in World War II.
Camels in World War II.
Sometime after the Battle of Stalingrad, many military units of the Soviet Red Army took to using camels in the southern theatre of the war in order to transport ammunition, fuel for tanks and aircraft, food, water for kitchens, fuel, and even wounded Red Army soldiers. The use of these animals as transport means was made necessary by the Kalmyk steppes' open terrain, their primitive roads and lack of water, as well as a shortage of adequate auxiliary vehicles in the Soviet armed forces.
In a notable case, a so-called "camel battalion" of around "one thousand camels" was carrying, for a "respectable distance," some "twelve thousand tons of various cargo," which would otherwise have required the use of approximately "134 trucks."
From Stalingrad to Berlin.
The 308th Rifle Division, formed on 21 March 1942 as part of the 1st Guards Army of the Soviet Red Army, started using a Bactrian camel brought over from Kazakhstan which the soldiers called (Russian for "grasshopper"), for transport of food and cookery material. It is said that the camel also made it easier for soldiers returning to the camp to locate their unit from the "tall and imposing animal, visible at a great distance".
The 308th Rifle Division, in honor of its heroic performance, was renamed the 120th Guards Rifle Division and, as part of the 3rd Army of Rokossovsky’s Front, took active part in the Battle of Stalingrad under Colonel Leonty Gurtyev (where it defended the factory), the liberation of Orel, Operation Bagration, the campaign for the recapture of Belarus, the East Prussian Offensive and finally the Battle of Berlin.
Kuznechik, carrying out its logistics duties in the rear, was to follow this mostly Siberian military formation all the way to Berlin, where its driver is said to have led the animal to the Reichstag to spit on the ruined building.
Other sources relate that Kuznechik was killed in a 1945 German air raid, near the Baltic Sea.
Decorations.
Kuznechik reportedly was awarded three wound stripes for injuries during various bombardments of the division as well as the Medal "For the Defence of Stalingrad".


Roger Slack

Charles Roger Slack (22 April 1937 – 24 October 2016) was a British-born plant biologist and biochemist who lived and worked in Australia (1962–1970) and New Zealand (1970–2000). In 1966, jointly with Marshall Hatch, he discovered C4 photosynthesis (also known as the Hatch Slack Pathway).
Biography.
Slack was born on 22 April 1937 in Ashton-under-Lyne, Lancashire, England; the first and only child of Albert and Eva Slack. He studied biochemistry at the University of Nottingham, where he graduated with a Bachelor of Science (Honours) in 1958, and a PhD in 1962. He married Pam Shaw in March 1963, and had two children.
From 1962, Slack worked as a biochemist at the David North Plant Research Centre in Brisbane, Queensland, Australia (funded by the Colonial Sugar Refining Co. Ltd). In 1970, he joined the Department of Scientific and Industrial Research in New Zealand. From 1989 until his retirement in 2000, Slack was a senior scientist at the newly formed Crown Research Institute for Crop & Food Research in Palmerston North.
Slack died in Palmerston North in 2016.
Roger Slack Award.
In 2007 the New Zealand Society of Plant Biologists renamed their annual award after Slack. The award is made to society members to recognise an outstanding contribution to the study of plant biology. It was renamed in recognition of his outstanding contribution as a plant biologist and biochemist in New Zealand, his role in the discovery of C4 photosynthesis (also known as the Hatch Slack Pathway), and his contribution as an early member of the New Zealand Society of Plant Biologists.
Bibliography.
Selected articles:


Tranquilizer

A tranquilizer refers to a drug which is designed for the treatment of anxiety, fear, tension, agitation, and disturbances of the mind, specifically to reduce states of anxiety and tension.
Tranquilizer, as a term, was first used by F.F. Yonkman (1953), from the conclusions of investigative studies using the drug reserpine, which showed the drug had a calming effect on all animals it was administered to. Reserpine is a centrally acting Rauwolfia alkaloid. The word directly refers to the state of tranquillity in a person and other animals.
The term is considered "popular" or "common", meaning it is not generally in use in the field of medicine. Specifically, it is used in reference to antipsychotic or neuroleptic medications.
The term is generally used as a synonym for sedative. When used by health care professionals, it is usually qualified or replaced with more precise terms:
Mood stabilizers might also be considered to belong to the classification of tranquilizing agents.


Phosphatidate cytidylyltransferase

Phosphatidate cytidylyltransferase () (also known as CDP- diacylglycerol synthase) (CDS) is the enzyme that catalyzes the synthesis of CDP-diacylglycerol from cytidine triphosphate and phosphatidate.
Thus, the two substrates of this enzyme are cytidine triphosphate, or CTP, and phosphatidate, whereas its two products are diphosphate and CDP-diacylglycerol.
CDP-diacylglycerol is an important branch point intermediate in both prokaryotic and eukaryotic organisms. CDS is a membrane-bound enzyme.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is CTP:phosphatidate cytidylyltransferase. Other names in common use include CDP diglyceride pyrophosphorylase, CDP-diacylglycerol synthase, CDP-diacylglyceride synthetase, cytidine diphosphoglyceride pyrophosphorylase, phosphatidate cytidyltransferase, phosphatidic acid cytidylyltransferase, CTP:1,2-diacylglycerophosphate-cytidyl transferase, CTP-diacylglycerol synthetase, DAG synthetase, and CDP-DG. This enzyme participates in glycerophospholipid metabolism and phosphatidylinositol signaling system.


G-CSF factor stem-loop destabilising element

The G-CSF factor stem-loop destabilising element (SLDE) is an RNA element secreted by fibroblasts and endothelial cells in response to the inflammatory mediators interleukin-1 (IL-1) and tumour necrosis factor-alpha and by activated macrophages. The synthesis of G-CSF is regulated both transcriptionally and through control of mRNA stability. In unstimulated cells G-CSF mRNA is unstable but becomes stabilised in response to IL-1 or tumour necrosis factor alpha, and also in the case of monocytes and macrophages, in response to lipopolysaccharide. It is likely that the presence of the SLDE in the G-CSF mRNA contributes to the specificity of regulation of G-CSF mRNA and enhances the rate of shortening of the poly(A) tail.


List of bioluminescent fungus species

Found largely in temperate and tropical climates, currently there are more than 75 known species of bioluminescent fungi, all of which are members of the order Agaricales (Basidiomycota) with one exceptional ascomycete belonging to the order Xylariales. All known bioluminescent Agaricales are mushroom-forming, white-spored agarics that belong to four distinct evolutionary lineages. The Omphalotus lineage (comprising the genera Omphalotus and "Neonothopanus") contains 12 species, the "Armillaria" lineage has 10 known species, while the Mycenoid lineage ("Mycena", "Panellus", "Prunulus", "Roridomyces") has more than 50 species. The recently discovered Lucentipes lineage contains two species, "Mycena lucentipes" and "Gerronema viridilucens", which belong to a family that has not yet been formally named. "Armillaria mellea" is the most widely distributed of the luminescent fungi, found across Asia, Europe, North America, and South Africa.
Bioluminescent fungi emit a greenish light at a wavelength of 520–530 nm. The light emission is continuous and occurs only in living cells. No correlation of fungal bioluminescence with cell structure has been found. Bioluminescence may occur in both mycelia and fruit bodies, as in "Panellus stipticus" and "Omphalotus olearius", or only in mycelia and young rhizomorphs, as in "Armillaria mellea". In "Roridomyces roridus" luminescence occurs only in the spores, while in "Collybia tuberosa", it is only in the sclerotia.
Although the biochemistry of fungal bioluminescence has not fully been characterized, the preparation of bioluminescent, cell-free extracts has allowed researchers to characterize the "in vitro" requirements of fungal bioluminescence. Experimental data suggest that a two-stage mechanism is required. In the first, a light-emitting substance (called "luciferin") is reduced by a soluble reductase enzyme at the expense of NAD(P)H. In the second stage, reduced luciferin is oxidized by an insoluble luciferase that releases the energy in the form of bluish-green light. Conditions that affect the growth of fungi, such as pH, light and temperature, have been found to influence bioluminescence, suggesting a link between metabolic activity and fungal bioluminescence.
All bioluminescent fungi share the same enzymatic mechanism, suggesting that there is a bioluminescent pathway that arose early in the evolution of the mushroom-forming Agaricales. All known luminescent species are white rot fungi capable of breaking down lignin, found in abundance in wood. Bioluminescence is an oxygen-dependent metabolic process and therefore may provide antioxidant protection against the potentially damaging effects of reactive oxygen species produced during wood decay. The physiological and ecological function of fungal bioluminescence has not been established with certainty. It has been suggested that in the dark beneath closed tropical forest canopies, bioluminescent fruit bodies may be at an advantage by attracting grazing animals (including insects and other arthropods) that could help disperse their spores. Conversely, where mycelium (and vegetative structures like rhizomorphs and sclerotia) are the bioluminescent tissues, the argument has been made that light emission could deter grazing.
The following list of bioluminescent mushrooms is based on a 2008 literature survey by Dennis Desjardin and colleagues, in addition to accounts of several new species published since then.


N-Ethyltryptamine

"N"-Ethyltryptamine (NET), or merely ethyltryptamine, is a tryptamine that is structurally related to "N"-methyltryptamine (NMT) and the psychedelic drugs "N","N"-dimethyltryptamine (DMT) and "N","N"-diethyltryptamine (DET).


Live single-cell imaging

In systems biology, live single-cell imaging is a live cell imaging technique that combines traditional live cell imaging and time-lapse microscopy techniques with automated cell tracking and feature extraction, drawing many techniques from high-content screening. It is used to study signalling dynamics and behaviour in populations of individual living cells. Live single cell studies can reveal key behaviours that would otherwise be masked in population averaging experiments such as western blots.
In a live single cell imaging experiment a fluorescent reporter is introduced into a cell line to measure the levels, localisation or activity of a signalling molecule. Subsequently, a population of cells is imaged over time with careful atmospheric control to maintain viability, and reduce stress upon the cells. Automated cell tracking is then performed upon these time series images, following which filtering and quality control may be performed. Analysis of features describing the fluorescent reporter over time, can then lead to modelling and generation of biological conclusions from which further experimentation can be guided.
History.
The field of live single-cell imaging began with work demonstrating that green fluorescent protein (GFP), found in the jellyfish "Aequorea victoria", could be expressed in living organisms. This discovery allowed researches to study the localisation and levels of proteins in living single cells, for example the activity of kinases, and calcium levels, through the use of FRET reporters, as well as numerous other phenotypes.
Generally, these early studies focused on the localisation and behaviour of these fluorescently labelled proteins at the subcellular level over short periods of time. However, this changed with pioneering studies looking at the tumour suppressor p53 and the stress and inflammation related protein NF-κB, revealing there levels and localisation respectively to oscillate over periods of several hours. Live single cell approaches were also applied around this time to understand signalling in single cell organisms including bacteria, where live studies allowed the dynamics of competence to be modelled, and yeast revealing the mechanism underpinning coherent cell cycle entry.
Experimental work flow.
Fluorescent reporters.
In any live single cell study, the first step is to introduce a reporter for our protein/molecule of interest into a suitable cell line. Much of the growth in the field has come from improved gene editing tools such as CRISPR, this leading to development of a wide variety of fluorescent reporters.
Fluorescent tagging uses a gene encoding a fluorescent protein that is inserted into the coding frame of the protein to be tagged. Texture and intensity features can be extracted from images of the tagged protein.
Molecules can also be tagged in vitro and introduced into the cell with electrophoresis. This enable the use of smaller and more photostable fluorophores but requires additional washing steps.
By engineering expression of FRET reporter such that donor and emitter fluorophores are only in close proximity when an upstream signalling molecule is either active or inactive, the donor to emitter fluorescence intensity ratio can be used as a measure of signalling activity. For example, in key early work using FRET reporters for live single studies FRET reporters of Rho GTPase activity were engineered.
Nuclear translocation reporters use engineered nuclear import and nuclear export signals, which can be inhibited by signalling molecules, to record signalling activity via the ration of nuclear reporter to cytoplasmic reporter.
Live imaging.
Live cell imaging of fluorescently labelled cells must then be performed. This requires simultaneous incubation of cells in stress free conditions whilst imaging is being performed. There are several factors that must be taken into account when choosing imaging conditions such as phototoxicity, photobleaching, tracking ease, rate of change of signalling activity, and Signal to noise. These all relate to imaging frequency and illumination intensity.
Phototoxicity can result from being exposed to large amounts of light over long periods of time. Cells will become stressed, which can lead to apoptosis. High frequency and intensity imaging can cause the fluorophore signal to decrease through photobleaching. Higher frequency imaging generally makes automated cell tracking easier. Imaging frequencies should be able to capture necessary changes to signalling activity. Low intensity imaging or poor reporters may prevent low levels of signalling activity within the cell from being detected.
Live cell tracking.
Following live cell imaging, automated tracking software is then employed to extract time series data from videos of cells. Live cell tracking is generally split into two steps, image segmentation of cells or their nuclei and cell/nuclei tracking based on these segments. Many challenges still exist in this stage of a live single cell imaging study. However recent progress has been highlighted in the field first objective comparison of single cell tracking techniques.
Quantitative phase imaging (QPI) is particularly useful for live cell tracking. As QPI is label-free, it does not induce phototoxicity, nor does it suffer from the photobleaching associated with fluorescence imaging. QPI offers a significantly higher contrast than conventional phase imaging techniques, such as phase-contrast microscopy. The higher contrast facilitates more robust cell segmentation and tracking than achievable with conventional phase imaging.
New techniques that use use a combination of traditional image segmentation techniques and deep learning to segment cells are also becoming more widely used as well.
Data analysis.
In the final stage of a live single-cell imaging study modelling and analysis of time series data extracted from tracked cells is performed. Pedigree tree profiles can be constructed to reveal heterogeneity in individual cell response and downstream signalling. A large overlap between analysis of single cell live data, and modelling of biological systems using ordinary differential equations exists. Results from this key data analysis step will drive further experimentation, for example by perturbing aspects of the system being studied and then comparing signalling dynamics with those of the control population.
Applications.
By analysing the signalling dynamics of single cells across entire populations, live single cell studies are now letting us understand how these dynamics affect key cellular decision making processes. For example, live single cell studies of the growth factor ERK revealed it to possess digital all-or-nothing activation. Moreover, this all-or-nothing activation was pulsatile, and the frequency of pulses in turn determined whether mammalian cells would commit to cell cycle entry or not. In another key example, live single-cell studies of CDK2 activity in mammalian cells demonstrated that bifurcation in CDK2 activity following mitosis, determined whether cells would continue to proliferate or enter a state of quiescence; now shown, using live single-cell methods, to be caused by stochastic DNA damage inducing upregulation of p21, which inhibits CDK2 activity. Moving forward, live single cell studies will now likely incooperate multiple reporters into single cell lines to allow complex decision making processes to be understood, however challenges still remain in scaling up live single cell studies.


Gordana Vunjak-Novakovic

Gordana Vunjak-Novakovic () is a Serbian American biomedical engineer. She is a University Professor at Columbia University, as well as the Mikati Foundation Professor of Biomedical Engineering and Medical Sciences. She also heads the laboratory for Stem Cells and Tissue Engineering at Columbia University. She is part of the faculty at the Irving Comprehensive Cancer Center and the Center for Human Development, both found at Columbia University. She is also an honorary professor at the Faculty of Technology and Metallurgy at the University of Belgrade, an honorary professor at the University of Novi Sad, and an adjunct professor at the Department of Biomedical Engineering at Tufts University.
Her focus is on engineering human tissues for regenerative medicine, stem cell research and modeling of disease. Together with her team she has published over 380 scientific papers, 70 book chapters and three books on tissue engineering. Vunjak-Novakovic has also given 380 invited lectures across the world and is named as co-inventor on 100 licensed, issued and pending patents. Building on these patents she co-founded four biotech companies: EpiBone, TARA Biosystems, Xylyx Bio, and Immplacate Health. Additionally, she is a frequent advisor to the federal government on tissue engineering and regenerative medicine.
Biography.
Vunjak received her B.S., M.S., and Ph.D. in chemical engineering from the University of Belgrade, in Belgrade, Serbia, her birthplace. After her postgraduate study in Germany, she returned as a faculty to the University of Belgrade in its Chemical Engineering Department. She was a Fulbright Fellow at Massachusetts Institute of Technology’s Harvard-MIT Division of Health Sciences and Technology from 1986 to 1987 and held joint appointments as research scientist at the Whitaker College of Health Sciences and Technology at MIT (1993-1998) and as adjunct professor in the Department of Biomedical Engineering at Tufts University (1994-2004). In 1998 she became a full-time principal research scientist with the Harvard-MIT Division of Health Science and Technology at MIT, where she collaborated, among others, with renowned biomedical engineer Robert S. Langer. In 2005, she accepted a position as full professor with the Department of Biomedical Engineering at Columbia University. She is married to Branko Novakovic, an architect, and they have a son Stasha who is practicing pulmonology and critical care in Miami.
Research.
Vunjak-Novakovic's numerous scholarly accomplishments have substantially impacted the field of tissue engineering in specific and the field of biomedical engineering in general. The focus of her research is on engineering functional human tissues, by an integrated use of stem cells, biomaterial scaffolds and bioreactors, which are culture systems designed to regulate and stimulate tissue development. In her work she has laid the theoretical and experimental foundation for the development of new biomaterials and scaffold architecture to regenerate tissue. For example, a series of 5 papers on bioreactors, seeding of polymer scaffolds for cartilage tissue engineering, cultivation parameters, and tissue construct characterization, published in 1998 and 1999 have been cited over 2,000 times. Building on these efforts, Prof. Vunjak-Novakovic continued to perform complex cell biological studies that address fundamental problems such as the growth and differentiation of stem cells for functional skeletal and cardiac mechanics, the growth of mammalian cells in microgravity environment, and the role of chondrocytes in cartilage tissue biomechanics. In ways not achieved by any other research team, Prof. Vunjak-Novakovic's group has succeeded to control cell growth, metabolism and function of engineered human tissues. This has garnered her highest praise and recognition of the scientific community. She is now starting to translate this foundation into clinical applications that promise to profoundly influence the way patients are treated and medicine is practiced.
Recognition.
In 2007, Vunjak-Novakovic became the first woman engineer to receive the distinction of giving the Director's Lecture at the National Institute of Health. In 2008, she was inducted into the Women in Technology International Hall of Fame, and in 2009, she was elected to the New York Academy of Sciences. One year later she received the Clemson Award of the Society of Biomaterials "for significant contributions to the literature on the science or technology of biomaterials." Vunjak-Novakovic is currently serving on the Council of NIBIB, and has previously served as a Chair of Fellows of the American Institute for Medical and Biological Engineering. She is a fellow of the Biomedical Engineering Society, a fellow of AAAS, and a founding fellow of TERMIS. She is a member of the Academia Europaea, Serbian Academy of Sciences and Arts, the Women in Technology International Hall of Fame, and one of Foreign Policy 100 leading global thinkers for 2014. She is the recipient of the Robert A. Pritzker Distinguished Lecture Award for 2017, the premier award of the Biomedical Engineering Society. As her research has made substantial breakthroughs in recent years, her work has also captured the imagination of the general public and was featured in "The New York Times", Scientific American, "Forbes Magazine", National Public Radio (NPR), and the BBC.
In 2012 she was elected to the National Academy of Engineering "for bioreactor systems and modeling approaches for tissue engineering and regenerative medicine," becoming the first woman at Columbia to ever earn that prestigious distinction. Two years later this was followed by the elections to the National Academy of Medicine, and the National Academy of Inventors.
In 2017, Professor Vunjak-Novakovic was appointed to the rank of University Professor at Columbia University, the institution's highest academic honor reserved for a small number of faculty who have made the most important contributions to their field of study, and serve the university as a whole. She appeared in 2018 as herself in the documentary film Tesla Nation.
In 2019, she was elected to the American Academy of Arts and Sciences.
In 2021, She was awarded the Sretenje order of the Republic of Serbia.


Diguanylate cyclase

In enzymology, diguanylate cyclase, also known as diguanylate kinase (), is an enzyme that catalyzes the chemical reaction:
2 Guanosine triphosphate ↔ 2 diphosphate + cyclic di-3',5'-guanylate
The substrates of diguanylate cyclases (DGCs) are two molecules of guanosine triphosphate (GTP) and the products are two molecules of diphosphate and one molecule of cyclic di-3’,5’-guanylate (cyclic di-GMP).
Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase (PDE).
Structure.
Diguanylate cyclases are characterized by the conserved amino acid sequence motifs “GGDEF” (Gly-Gly-Asp-Glu-Phe) or “GGEEF” (Gly-Gly-Glu-Glu-Phe), which constitute the domain of the DGC active site. These domains are often found coupled to other signaling domains within multidomain proteins. Often, GGDEF domains with DGC activity are found in the same proteins as c-di-GMP-specific phosphodiesterase (PDE) EAL (Glu-Ala-Leu) domains.
DGC is thought to only be active as a dimer consisting of two subunits, both with GGDEF domains. The active (or catalytic) site is located at the interface between the two subunits, each binding one molecule of GTP. (See Activation mechanism and Regulation section for more information)
Weak sequence similarity and pronounced secondary structure similarity between GGDEF domains and the catalytic domains of adenylate cyclases (AC) have led to the hypothesis that DGCs and ACs share a similar fold. This was verified with the resolution of the crystal structure of the DGC PleD from "Caulobacter crescentus" in complex with c-di-GMP. As shown in the figure, active PleD, shown as a dimer, is composed of the catalytic DCG domain (labeled DGC) and two CheY-like receiver domains (labeled D1/D2). The DGC domain of each subunit is linked to the two CheY-like domains by a flexible peptide linkage chain. The DCG domain closely resembles the domain of the AC catalytic core which consists of a five-stranded β-sheet surrounded by helices.
As of mid-2011, 11 crystal structures of confirmed or putative DGCs have been solved, with PDB accession codes , , , , , , , , , , and .
Biological function.
Diguanylate cyclase participate in the formation of the ubiquitous second messenger, cyclic-di-GMP, involved in bacterial biofilm formation and persistence. The GGDEF domain was first identified in the regulatory protein, PleD of the bacterium "Caulobacter crescentus". It was later noted that numerous bacterial genomes encoded multiple proteins with a GGDEF domain. "Pseudomonas aeruginosa" PAO1 has 33 proteins with GGDEF domains, "Escherichia coli" K-12 has 19, and "Vibrio cholerae" O1 has 41. In the cell cycle of "Caulobacter crescentus", DGC PleD is known to control pole morphogenesis. In "Pseudomonas fluorescens" DGC WspR activity is hypothesized to be partially responsible for the wrinkly spreader (WS) phenotype. In "Pseudomonas aeruginosa", WspR has also been known to control autoaggregation.
"Role of DGC in C. crescentus cell cycle".
During the cell cycle of "C. crescentus", proteins with GGDEF and EAL domains are separated towards the two distinct poles. The active form of diguanylate cyclase PleD localizes to the stalked pole of differentiating "C. crescentus" cells. It has been suggested that the function of PleD is two-fold. PleD is responsible for turning off flagellum rotations and inhibiting motility before genome replication begins and also for regenerating motility after differentiation has completed.
Activation Mechanism and Regulation.
The crystal structure of the "C. crescentus" diguanylate cyclase, PleD, contains three domains; a GGDEF domain with diguanylate cyclase activity and two CheY-like receiver domains (D1/D2). As seen in the figure, the active form of PleD is a dimer which forms by phosphorylation of the first receiver domain (D1). Phosphorylation of the receiver domain increases the dimerization affinity by approximately 10-fold over non-phosphorylated domains.
Inhibition of DGC activity is thought to be allosteric and non-competitive. Cyclic di-GMP binds to interface between the DGC and D2 domains stabilizing the open structure and preventing catalysis. Strong product inhibition has been observed with a K of 0.5 μM.
Though the exact catalytic mechanism has not been resolved, it is hypothesized that the dimerized structure of PleD facilitates interaction of the two GTP molecules within the DGC active site for cyclization. A proposed mechanism by Chan et al. indicates that the 3'-OH group of the GTP is deprotonated by a glutamic acid residue (E370) to allow for intermolecular nucleophilic attack of the α-phosphate. The pentachoordinated transition state created through this nucleophilic attack is possibly stabilized by a Lysine residue (K332).


Deoxyuridine monophosphate

Deoxyuridine monophosphate (dUMP), also known as deoxyuridylic acid or deoxyuridylate in its conjugate acid and conjugate base forms, respectively, is a deoxynucleotide.
It is an intermediate in the metabolism of deoxyribonucleotides.
Biosynthesis.
Deoxyuridine monophosphate (dUMP) is the deoxygenated form of uridine monophosphate (UMP), and is the precursor to deoxythymine monophosphate (dTMP), a component of DNA nucleotide biosynthesis. By replacing the hydroxyl group at the 2' carbon of ribose with a hydrogen, UMP becomes deoxygenated to dUMP.
The synthesis of deoxyuridine monophosphate (dUMP) is a multi-step process that begins with uridine monophosphate (UMP), the product of pyrimidine biosynthesis. The enzyme nucleoside monophosphate kinase converts UMP and ATP to uridine diphosphate (UDP) and ADP.
In the presence of excess ATP, the enzyme ribonucleotide reductase initiates a chain reaction with UDP, which catalyzes the formation of deoxyuridine diphosphate (dUDP), which is then converted to deoxyuridine triphosphate (dUTP), then deoxyuridine monophosphate (dUMP) via the addition or removal of phosphate groups.


Colforsin

Colforsin (INN) is a water-soluble derivative of forskolin.


Amphichiral link


Deoxyinosine monophosphate

Deoxyinosine monophosphate (dIMP) is a nucleoside monophosphate and a derivative of inosinic acid. It can be formed by the deamination of the purine base in deoxyadenosine monophosphate (dAMP). The enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase, encoded by YJR069C in "S. cerevisiae" and containing (d)ITPase and (d)XTPase activities, hydrolyses dITP, resulting in the release of pyrophosphate and dIMP.


Caladrius Biosciences

Caladrius Biosciences is an American biopharmaceutical company active in the field of stem cell therapy and regenerative medicine, particularly (in 2012) of cardiovascular disease.
Founded in 1980, the company was formerly known as Corniche Group Inc, Phase III Medical Inc, and NeoStem, Inc., it adopted its current name in 2015.
Cardiovascular disease.
In 2012 it started a phase 2 clinical trial of AMR-001 (NBS10), an autologous bone marrow-derived cell therapy enriched for CD34+ cells, for acute myocardial infarction. Initial results included a statistically significant mortality benefit.


Guanylin

Guanylin is a 15 amino acid polypeptide that is secreted by goblet cells in the colon. Guanylin acts as an agonist of the guanylyl cyclase receptor GC-C and regulates electrolyte and water transport in intestinal and renal epithelia. Upon receptor binding, guanylin increases the intracellular concentration of cGMP, induces chloride secretion and decreases intestinal fluid absorption, ultimately causing diarrhoea. The peptide stimulates the enzyme through the same receptor binding
region as the heat-stable enterotoxins.
Researches have found that a loss in guanylin expression can lead to colorectal cancer due to guanylyl cyclase C's function as an intestinal tumor suppressor. When guanylin expression was measured on over 250 colon cancer patients, more than 85% of patients had a loss of guanylin expression in cancerous tissue samples by 100-1000 times when compared to the same patients's nearby healthy colon tissue. Another study done on genetically engineered mice found that mice on a high calorie diet had reduced guanylin expression in the colon. This loss of expression then resulted in guanylyl cyclase C inhibition and the formation of tumors, therefore linking diet-induced obesity with colorectal cancer.
Human proteins containing this domain.
GUCA2A; GUCA2B;
Structure.
This peptide has two topogies, both isoforms are shown below:


Cryobacterium psychrophilum

Cryobacterium psychrophilum is the type species of the bacterial genus "Cryobacterium". It is an obligately psychrophilic, Gram-positive irregular rod-shaped actinomycete, with type strain JCM 1463 (=IAM 12024 =ATCC 43563 =IFO 15735 =NCIMB 2068).


Dermaseptin

Dermaseptins are a family of peptides isolated from skin of the frog genus "Phyllomedusa".
The sequence of the dermaseptins varies greatly but due to the presence of lysine residues all are cationic and most have the potential to form amphipathic helices in water or when integrated with the lipid bilayer of the bacterial membrane. Clear separation of two lobes of positive and negative intramolecular electrostatic potential is thought to be important in cytotoxic activity. Dermaseptins are typically 27-34 amino acid residues in length and were the first vertebrate peptides demonstrated as having a lethal effect on the filamentous fungi implicated in severe opportunistic infections accompanying immunodeficiency syndrome and immunosuppressive drug therapy.
Dermaseptin use in a novel drug delivery system has been proposed. The system is based on the affinity of dermaseptins for the plasma membrane of human erythrocytes. After transient loading of the cells with the non-toxic dermaseptin S4 analogue K4–S4(1–13)a, the peptide is transported in the systemic circulation to distant microbial targets. Upon reaching a microorganism for which it has greater affinity the dermaseptin derivative is spontaneously transferred to the microbial membrane where it exerts its membrane-lytic activity.


Mycena chlorophos

Mycena chlorophos is a species of agaric fungus in the family Mycenaceae. First described in 1860, the fungus is found in subtropical Asia, including Japan, Taiwan, Polynesia, Indonesia, and Sri Lanka, in Australia, and Brazil. Fruit bodies (mushrooms) have pale brownish-grey sticky caps up to in diameter atop stems long and up to a millimeter thick. The mushrooms are bioluminescent and emit a pale green light. Fruiting occurs in forests on fallen woody debris such as dead twigs, branches, and logs. The fungus can be made to grow and fruit in laboratory conditions, and the growth conditions affecting bioluminescence have been investigated.
Taxonomy.
The species was first described scientifically by Miles Berkeley and Moses Ashley Curtis in 1860 as "Agaricus chlorophos". The original specimens were collected from the Bonin Islands by American botanist Charles Wright in October 1854 as part of the North Pacific Exploring and Surveying Expedition of 1853–56. Pier Andrea Saccardo transferred the species to the genus "Mycena" in an 1887 publication. Daniel Desjardin and colleagues redescribed the species and set a lectotype specimen in 2010.
In 1860 Berkeley and Curtis described the species "Agaricus cyanophos" from material also collected from the Bonin Islands. This material was found near the location that the original specimens of "M. chlorophos" were found, but a couple of weeks later. Japanese mycologists Seiya Ito and Sanshi Imai studied these collections in the late 1930s, and concluded that "Agaricus cyanophos" was the same species as "M. chlorophos", despite differences in cap shape, gill attachment, and the color of emitted light. Desjardin and colleagues agreed with this determination after examining the type material of both taxa. "M. chlorophos" is classified in the section "Exornatae" of the genus "Mycena". Other luminescent species in this section are "M. discobasis" and "M. marginata". Some authors have considered "M. illuminans" to be synonymous with "M. chlorophos" due to their morphological similarity, but molecular analysis has shown that they are distinct species.
In Japan, the mushroom is known as "yakoh-take", or "night-light mushroom". In the Bonin Islands it is called "Green Pepe".
Description.
The cap is initially convex before flattening out (sometimes forming a central depression), and measures up to in diameter. The cap has radial grooves extending to nearly the center, and sometimes develops cracks in the margin, which has small rounded teeth. Its color is pale brownish gray that fades after expansion, and it is somewhat sticky. The white stem is long by 0.3–1 mm thick, hollow, and translucent. It has tiny hairs on the surface. The base of the stem is disc-shaped or somewhat bulbous, measuring 1–2.5 mm wide. The thin gills are free from attachment to the stem, or are adnexed (narrowly attached) to a slight collar encircling the stem. Initially white then grayish in color, they are somewhat crowded, with 17–32 full-length gills and 1 to 3 tiers of lamellulae (shorter gills that do not extend fully from the cap margin to the stem). The gills are 0.3–1 mm wide with micaceous edges. The flesh is very thin, and has a strong odor of ammonia. Both the caps and the gills are bioluminescent, while the mycelia and stems have little to no luminescence.
The spores are white, smooth, roughly elliptical, and have dimensions of 7–8.5 by 5–6 μm. The basidia (spore-bearing cells) are 17–23 by 7.5–10 μm, and four-spored with sterigmata around 3 μm long. The paraphyses are 5–8 μm wide, shorter than the basidia, more abundant and form a somewhat gelatinous layer. The cheilocystidia (cystidia on the cap edge) are 60 by 7–21 μm, hyaline, conical or ventricose (inflated). The tips of the cheilocystidia are drawn out to a point, or have a short appendage measuring 15 by 2–3 μm, which is sometimes branched, and is thin or slightly thick-walled. There are no cystidia on the gill face (pleurocystidia). Pileocystidia (cystidia on the surface of the cap) are club-shaped, measuring 25–60 by 13–25 μm. They are somewhat thick-walled, and spiny on the exposed surface with short simple outgrowths extending up to 3 μm long. The pileocystidia are joined together and form a continuous layer over the young cap, but break up as the cap expands. The caulocystidia (cystidia on the stem) are conical or lance-shaped, hyaline, and smooth, with walls that are thin or slightly thickened. They measure up to 300 by 10–25 μm, but are shorter in the upper regions of the stem. Clamp connections are present in the hyphae of all tissues.
Similar species.
The two other luminescent species of "Mycena" section "Exornatae" are similar in appearance to "M. chlorophos". "M. discobasis" fruit bodies have paler caps; microscopically, they have larger spores measuring 9.9 by 6.7 μm, and lack the short apical appendage found on "M. chlorophos" cheilocystidia. "M. margarita" has smaller spores averaging 6.9 by 4.4 μm, smaller cheilocystidia, and loop-like clamp connections.
Habitat and distribution.
Fruit bodies of "Mycena chlorophos" are found in forests, where they grow in groups on woody debris such as fallen twigs, branches, and bark. In the Japanese Hachijo and Bonin Islands, mushrooms occur predominantly on decaying petioles of the palm "Phenix roeberenii". The fungus requires a proper range of humidity to form mushrooms; for example, on Hachijo Island, fruiting only occurs in the rainy seasons in June/July and September/October when the relative humidity is around 88%, usually the day after rain falls. Experimental studies have shown that mushroom primordia that are too wet become deformed, while conditions that are too dry cause the caps to warp and break because the delicate gelatinous membrane covering them is broken.
In Asia, the species has been found in Japan, Taiwan, Polynesia, Java, and Sri Lanka. In Japan, the fungus is becoming more scarce as its natural habits are decreasing. Several Australian field guides have reported the species from that country. The fungus has also been recorded several times from Brazil. "Mycena chlorophos" was one of several fungi featured in a set of postage stamps issued in Samoa in 1985.
Bioluminescence studies.
Since the mushroom is small, and fruits in only a limited season in a small area, researchers have investigated the conditions needed to artificially cultivate the species in laboratory conditions, in order to have more material to study the mechanism of bioluminescence, and to help preserve the species. The optimum temperature for the growth of mycelia is , while the optimum for the growth of primordia is . These temperatures are consistent with the subtropical climate in which the species is typically found. Maximum luminescence occurs at 27 °C, and about 25–39 hours after the primordia begin to form, when the cap has fully expanded. At 21 °C, luminescence persists for about 3 days, and becomes undetectable to the naked eyes about 72 hours after primordium initiation.


Anne Beloff-Chain

Anne Ethel Beloff-Chain, Lady Chain (26 June 1921 – 2 December 1991) was a British biochemist. She worked at the Istituto Superiore di Sanità (1948–1964), Imperial College London (1964–1986) and the University of Buckingham (1986–1991). Her research focused on carbohydrate metabolism and the hormones involved in diabetes and obesity.
Early life.
Anne Ethel Beloff was born in 1921 in Hampstead to Semion (Simon) Beloff (born Semion Rubinowicz) and Maria (Marie) Katzin. Her parents were of Russian–Jewish background, and her siblings included the historian Max Beloff, Baron Beloff, the psychologist John Beloff, the journalist Nora Beloff, and the politician Renee Soskin. Her paternal great-grandmother was Leah Horowitz-Winograd, the sister Eliyahu Shlomo Horowitz-Winograd and a descendant of the Hasidic master, Shmelke Horowitz of Nikolsburg (1726-1778). She earned a degree in chemistry from University College London in 1942 before completing a PhD in the biochemistry of skin burns with Rudolph Peters at the University of Oxford. She visited Harvard Medical School in 1946 to perform research and returned to the UK in 1948. In the same year she married Ernst Boris Chain, a biochemist who had won the Nobel Prize in Physiology or Medicine in 1945, and moved with him to Rome.
Career.
Beloff-Chain worked at Italy's Istituto Superiore di Sanità (National Institute of Health) with Chain from 1948 to 1964, and held the position of chief research scientist. Her research focused on carbohydrate metabolism and the mechanism of action of insulin in hormonal control of diabetes and obesity. One of her most significant discoveries was that levels of beta-cell-tropin, an insulin secretagogue hormone, were elevated in the blood of obese individuals.
In 1964, Beloff-Chain and her husband were recruited by Imperial College London and her family returned to London, where she took up a biochemistry teaching post at Imperial College London. She was promoted to professor of biochemistry in 1983, but she decided to leave with her research team in 1985. A £250,000 new laboratory was built and she became a professor at the University of Buckingham in 1986. At Buckingham, she received funding from the Clore Foundation to establish and head the Department of Biochemistry, where she worked until her death.
Death and legacy.
She died on 2 December 1991 in Camden Town, in northwest London. She is best remembered for her significant discovery that levels of beta-cell-tropin, an insulin secretagogue hormone, were elevated in the blood of obese individuals.


Molybdenum cofactor cytidylyltransferase

Molybdenum cofactor cytidylyltransferase (, "MocA", "CTP:molybdopterin cytidylyltransferase", "MoCo cytidylyltransferase", "Mo-MPT cytidyltransferase") is an enzyme with systematic name "CTP:molybdenum cofactor cytidylyltransferase". This enzyme catalyses the following chemical reaction:
Catalyses the cytidylation of the molybdenum cofactor.


Square knot (mathematics)

In knot theory, the square knot is a composite knot obtained by taking the connected sum of a trefoil knot with its reflection. It is closely related to the granny knot, which is also a connected sum of two trefoils. Because the trefoil knot is the simplest nontrivial knot, the square knot and the granny knot are the simplest of all composite knots.
The square knot is the mathematical version of the common reef knot.
Construction.
The square knot can be constructed from two trefoil knots, one of which must be left-handed and the other right-handed. Each of the two knots is cut, and then the loose ends are joined together pairwise. The resulting connected sum is the square knot.
It is important that the original trefoil knots be mirror images of one another. If two identical trefoil knots are used instead, the result is a granny knot.
Properties.
The square knot is amphichiral, meaning that it is indistinguishable from its own mirror image. The crossing number of a square knot is six, which is the smallest possible crossing number for a composite knot.
The Alexander polynomial of the square knot is
which is simply the square of the Alexander polynomial of a trefoil knot. Similarly, the Alexander–Conway polynomial of a square knot is
These two polynomials are the same as those for the granny knot. However, the Jones polynomial for the square knot is
This is the product of the Jones polynomials for the right-handed and left-handed trefoil knots, and is different from the Jones polynomial for a granny knot.
The knot group of the square knot is given by the presentation
This is isomorphic to the knot group of the granny knot, and is the simplest example of two different knots with isomorphic knot groups.
Unlike the granny knot, the square knot is a ribbon knot, and it is therefore also a slice knot.


Automated pipetting system

An automated pipetting system is generally a device which performs programmed transfers of liquid between preselected groups of containers.
The word "pipetting" is referring to the laboratory manual tool called pipette, which is commonly used in molecular biology, analytical chemistry, and medical tests, to transport a measured volume of liquid. Moreover, its performances are regulated by the International Standard ISO8655-1:2002.
Automated pipetting systems are also commonly known as Liquid Handling Robots; nevertheless the latter definition is preferred whenever add-on modules are present (e.g. laboratory shaker), while the former typically focuses on liquid transfer property.
One of main advantages of these devices is the ability to enhance the reproducibility and the throughput of laboratory experiments.
Components.
The vast majority of automated pipetting systems have the following 'structural' components:
Pipetting head.
The pipetting head is the mechanical component designed for liquid transfer. The majority of pipetting heads are based on a peristaltic pump system, while some anthropomorphic systems directly use manual pipettes.
A pipetting head can be multi-channel or single-channel: while the former has higher throughput, the latter has greater flexibility and reproducibility.
For accurate placement into the source and destination containers, the pipetting head is placed on an automated axis system, typically based on servo motors or stepper motors.
User interface.
The user interface allows communication between the user and the system via a PC or a touchscreen. The most advanced user interfaces let users design their own experiments which are to be carried out on the system.
Working area.
The working area is the zone where liquid dispensing takes place, and it is the area where the pipetting head can move.
It contains holders that both hold the containers in which liquids are stored, and also allow the recognition of the position of the source and destination containers. The recognition of their position can be made 'statically' (off-line calibration of the position) or 'dynamically' (e.g. vision-controlled spatial localization).
Waste.
The waste container is a special container which stores disposable tips used by the system. It may also be used to throw away excess of liquid or washing buffer.
Functionality.
An automated pipetting system obtains a volume of liquid from a source by creating suction, or "aspirating", and dispensing this liquid over the destination container. This is achieved by the pipetting head installed on the system.
Liquids are not in direct contact with the pipetting head, but they are held by a structure called the tip. Tips can be permanent structures or disposable conical pieces. Disposable tips, in general made from injection molded plastic (typically polypropylene), have the advantage of being discarded between liquid transfers thus removing any chance of cross contamination. The choice of the most suitable tip mainly depends on the dispensing volume set on the pipetting head.
Some tips are equipped with filter to prevent aerosol entering the pipette, which can be a source of contamination or cause of deterioration of the pipette.
Critical parameters.
There are some critical parameters which affect liquid transfer in automated pipetting system; the most common are listed below :
Curiosity.
The first manual pipette was patented in 1950s by G.S. Riggs and the first automated analyzing apparatus less than ten years after.


Murepavadin

 Murepavadin also known as POL7080 is a "Pseudomonas" specific peptidomimetic antibiotic. It is a synthetic cyclic beta hairpin peptidomimetic based on the cationic antimicrobial peptide protegrin I (PG-1) and the first example of an outer membrane protein-targeting antibiotic class with a novel, nonlytic mechanism of action, highly active and selective against the protein transporter LptD of "Pseudomonas aeruginosa". In preclinical studies the compound was highly active on a broad panel of clinical isolates including multi-drug resistant "Pseudomonas " bacteria with outstanding "in vivo" efficacy in sepsis, lung, and thigh infection models. Intravenous murepavadin is in development for the treatment of bacterial hospital-acquired pneumonia and bacterial ventilator-associated pneumonia due to "Pseudomonas aeruginosa".
Discovery and structure.
The host defense antimicrobial peptide protegrin I (PG-1), exhibits broad-spectrum antimicrobial activity and good activity against multi-drug resistant Gram-negative pathogens, with a mechanism consistent with membrane disruption via pore formation. However, PG-1 exhibits unfavorable drug properties and also exhibits significant hemolysis and, as such, has limited clinical use. PG-1 contains 18 amino acids and is ordered into an anti-parallel β-strand by two disulfide bridges. A fully synthetic cyclic peptide-like molecule containing a D-proline–L-proline template grafted into a peptidomimetic scaffold to simulate and stabilize the beta hairpin conformation exhibited by PG-1 was used to generate a diverse library of peptidomimetic macrocycles which were screened for antibacterial activity. Variants in this 14-residue protein epitope mimetic (PEM) library such as the peptidomimetic L8-1 had an antimicrobial activity like that of PG-1 but with reduced hemolytic activity on human red blood cells. Iterative rounds of synthesis generated analogues with an increasingly potent and selective profile producing nanomolar range compounds specifically against Pseudomonas spp. at the expense of broad-spectrum activity. Final optimization led to the discovery of murepavadin, with remarkable Pseudomonas-specific activity "in vitro" and "in vivo" that has high plasma stability across species and is non-hemolytic at 100 µg/mL. Structure–activity relationship (SAR) studies showed that aromatic side chains of Trp2 and Trp8 are very important for antibiotic activity, while nuclear magnetic resonance studies showed that these potent D-pro-L-pro antibiotic derivatives had a stable β- hairpin conformation in aqueous solution whereas related derivatives with the D-pro-L-pro template inverted to L-pro-D-pro, shows no stable hairpin conformation and the antimicrobial activity was lost, suggesting that the β-hairpin structure is crucial for interaction with the bacterial target.
Mechanism of action.
Murepavadin functions through a novel mechanism of action by binding to the lipopolysaccharide transport protein D (LptD), an outer membrane protein involved in lipopolysaccharide biogenesis in Gram-negative bacteria. By binding to LptD, murepavadin inhibit the lipopolysaccharide transport function of LptD and causes lipopolysaccharide alterations in the outer membrane of the bacterium and, ultimately, cell death.
Spectrum of activity.
Murepavadin exhibits a specific and potent bactericidal activity "in vitro" against "Pseudomonas aeruginosa" including carbapenemase-producing and colistin-resistant isolates and was shown to be largely inactive against other Gram-negative bacteria, and Gram-positive bacteria. When tested in a large minimum inhibitory concentration surveillance study, against 1219 contemporary clinical isolates from the USA, Europe, and China of which 28% were multi-drug resistant strains, murepavadin exhibited a potent antimicrobial activity having a minimum inhibitory concentration for 90% of strains of 0.12 mg/L. There were no significant differences between geographic locations, and there was little difference in activity between multi-drug resistant/and non-multi-drug resistant isolates and no cross-resistance was observed with any other antimicrobial tested which supports its novel mechanism of action. Murepavadin showed outstanding "in vivo" efficacy in mouse sepsis (ED50 of 0.25 - 0.55 mg/kg) and lung and thigh infection models. It displays linear pharmacokinetics, is dose proportional with a good penetration into the epithelial lung fluid which underscores its potent "in vivo" activity in lung infection models including extensively drug-resistant isolates. In phase I clinical trial in healthy volunteers, single doses were well tolerated at plasma concentrations expected to meet or exceed efficacious levels, with no serious adverse events reported. The favorable "in vitro" and "in vivo" properties of murepavadin combined with an appropriate safety pharmacology and toxicology profile led to the clinical development of murepavadin for the treatment of serious infections caused by "Pseudomonas aeruginosa". Murepavadin successfully completed phase-II clinical tests in hospital patients with life-threatening "Pseudomonas" lung infections and is in phase III development for the treatment of bacterial hospital-acquired and ventilator-associated bacterial due to "Pseudomonas aeruginosa" infection.


NSP6 (rotavirus)

Gene 11 of Rotavirus encodes a nonstructural protein, NSP5 and also encodes NSP6, from an out of phase open reading frame. In contrast to the other rotavirus non-structural proteins, NSP6 was found to have a high rate of turnover, being completely degraded within 2h of synthesis. NSP6 was found to be a sequence independent nucleic acid binding protein, with similar affinities for ssRNA and dsRNA.


Kliment Timiryazev

Kliment Arkadievich Timiryazev (; – 28 April 1920) was a Russian botanist and physiologist and a major proponent of the Evolution Theory of Charles Darwin in Russia. He founded a faculty of vegetable physiology and a laboratory at the Petrovskoye Academy.
Biography.
Timiryazev was born to Arkady Semyenovich Timiryazev, a Russian statesman, and Adelaida Bode, an English woman of French origin, who later received Russian citizenship. He had at least three brothers: (1835–1906), a military officer, (1837–1903), a specialists in statistics, and Vasily (c. 1840–1912), a writer. Timiryazev was first educated by private teachers at home. In 1861 he entered the Saint Petersburg University and graduated with honors from the faculty of physics and mathematics in 1866. Two years later he published his first article, on a device for studying breakdown of carbon dioxide, and was sent abroad, where he studied under Wilhelm Hofmeister, Robert Bunsen, Gustav Kirchhoff, Marcellin Berthelot, Hermann von Helmholtz, Jean-Baptiste Boussingault and Claude Bernard. Upon returning to Russia in 1871 he defended a PhD on spectral analysis of chlorophyll and was appointed as professor of Petrov's Academy of Agriculture, until its closure in 1892. Since 1877 he also lectured at the Moscow State University. His research work was devoted to photosynthesis-related phenomena. He also pioneered the use of greenhouses for agricultural research in Russia, which he initiated in early 1870s. He was a member of the Russian Academy of Sciences (since 1890), Royal Society (1911) and Botanical Society of Scotland (1911), and an honorary professor of the Saint Petersburg University, Kharkov University, University of Glasgow (1901), University of Cambridge (1909) and University of Geneva (1909).
Darwinism.
Timiryazev was a major proponent of the evolution theory of Charles Darwin in Russia. In 1877, he visited and met Darwin at Down House.
Timiryazev promoted Darwinism in his works and prepared a Russian translation of "On the Origin of Species". However, he was highly critical of the term "struggle for existence" which he rejected. He believed that it was an unfortunate metaphor with negative social implications and stated that Darwinism could be taught without using the word "struggle".
At the University of Moscow, Alexander Oparin attended private lectures of Timiryazev. These lectures on evolution were highly influential to Oparin. He also lectured on Darwinism at his flat in Moscow.
Legacy.
Timiryazev Agricultural Academy, the Timiryazevskaya station of the Moscow Metro, the lunar crater "Timiryazev" and the asteroid 6082 Timiryazev are named after him. In Vinnytsia there is the Regional Universal Scientific Library named after Kliment Timiryazev. The in Moscow is also named after him.
At the beginning of the Tverskoy Boulevard in Moscow there is a statue of Timiryazev which was unveiled on 4 November 1923, sculpted by Sergey Merkurov and laid out by the architect Osipov. Timiryazev is depicted in the gown of Cambridge University where he was awarded an honorary doctorate. The granite pedestal bears the inscription of 'the curve of plant physiology' which Timiryazev elucidated. In October 1941 the statue was overturned by a Fascist bomb, but after a few hours it was back in its place. Its lower half still bears the marks caused by bomb splinters.


Carpitalpa


Cyclamide

Cyclamides are a class of oligopeptides, produced by cyanobacteria algae strains, such as microcystis aeruginosa and can be toxic. Cyclamides are synthesized through ribosomic pathways.


5-OH-DPAT

5-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with selectivity for the D2 receptor and D3 receptor subtypes. Only the ("S")-enantiomer is active as an agonist, with the ("R")-enantiomer being a weak antagonist at D2 receptors. Radiolabelled 11C-5-OH-DPAT is used as an agonist radioligand for mapping the distribution and function of D2 and D3 receptors in the brain, and the drug is also being studied in the treatment of Parkinson's disease.


Photobacterium

Photobacterium is a genus of gram-negative bacteria in the family "Vibrionaceae". Members of the genus are bioluminescent, that is they have the ability to emit light.
Many species, including "Photobacterium leiognathi" and "Photobacterium phosphoreum", live in symbiosis with marine organisms.
Species such as "Photobacterium profundum" are adapted for optimal growth in the deep cold seas making it both a psychrophile (an organism capable of growth and reproduction in cold temperatures) and a piezophile (an organism which thrives at high pressures).
Taxonomy.
There are currently 16 species with numerous subspecies known within the genus "Photobacterium". The development of 16S RNA sequencing has led to many species being shifted into and out of this genus. "Photobacterium" can be distinguished from other genera based on identifiable characteristics.
Ecology.
"Photobacterium" are primarily marine organisms (hence the use of sodium for growth). They may be free-living or found as colonies associated with certain species of fish. These organisms do not contain any pigmentation and therefore will appear white or colorless. When there is a high density of cells forming a colony, they will exhibit fluorescence. However, the fluorescence is based on the accumulation of autoinducers which is proportional to cell density and therefore free-living photobacterium will not fluoresce. Their association with fish may be: symbiotic growth within fish for the formation of light organs, as a neutral entity on the surface or within the intestines of fish, as decomposers of dead fish, or as an agent of disease.
Pathogenicity.
Some of the 15 known species of "Photobacterium" have evolved into pathogens of marine life. Some of these diseases affect commercially important fish and can therefore indirectly impact human health through their consumption. This genus has been shown to degrade the chitin of the Deep Sea Tanner Crab ("Chionoecetes tanneri"). The species "Photobacterium damselae" are among the most virulent and are divided into two subspecies: "piscicida" and "damsela". "P. damselae" subspecies "piscicida" is the causative agent of fish pasteurellosis. Bacterial colonies grow on the infected fish's spleen and kidney, eventually leading to mortality. This disease accounts for severe losses in some fish farming enterprises with some of the most susceptible fish including Yellowfin tuna ("Thunnus albacares"), certain Seabreams ("Sparus" spp.), Striped bass ("Morone saxatilis"), and White perch ("Morone americana"). This subspecies is not pathogenic for humans.
"Photobacterium damselae" subspecies "damsela".
Fish-virulent strains of this subspecies of "P. damselae" cause septicemia in species of fish such as; damselfish (Family Pomacentridae), eels ("Anguilla anguilla"), brown sharks ("Carcharhinus plumbeus"), Yellowtails ("Seriola quinqueradiata"), seabreams ("Sparus" spp.) and turbots ("Scophthalmus" spp.). This subspecies has been shown to be pathogenic for humans as it has been isolated from human wounds and has been shown to cause primary septicimia in healthy humans.
Symptoms of "Photobacteria damselae" subspecies "damselae".
Fish infected by the subspecies "damselae" initially experience a reduced appetite accompanied by lethargicness and ulcerative lesions along their flank and head regions. Their stomachs will distend and they will experience extensive hemorrhaging especially in their eyes, mouth, and musculature. There will also be petechiation of the gills and liver along with the characteristic accumulation of mucus around the gills. It has been noted that the infected fish will swim violently a few minutes before death occurs
Transmission/infection of "Photobacterium damselae" subspecies "damsela".
Evidence of epizootic outbreaks gained from an increase in ulcers noted among the fish populations seem to correlate to warmer seasons, suggesting a seasonal distribution in the incidence of the disease, dependent upon the waters temperature and salinity along with a decreased resistance caused by physiological changes experienced by the host during sexual maturity.
Seawater is the most likely mode of transmission of the virulent cells of the pathogen. Once it comes into contact with the outer surface of the fish, it is able to adhere to skin and resist the bactericidal action of the skin mucus layer, thus suggesting that the skin is the site of entry into the host. This bacterium could therefore represent a significant threat to aquacultured fish species, especially those living in crowded and stressed conditions, where the spread of the disease could be accelerated through direct contact and thus pose a threat to humans.
References.
Hilgarth, Maik et al. “Photobacterium Carnosum Sp. Nov., Isolated from Spoiled Modified Atmosphere Packaged Poultry Meat.” Systematic and Applied Microbiology 41.1 (2018): 44–50.


Intectin

Intectin is a Ly-6 family protein which is anchored to glycosylphosphatidylinositol on intestinal epithelial cells. Intectin has been shown to maintain the integrity of the intestinal wall by inducing apoptosis of intestinal epithelial cells upon exposure to dietary palmitic acid. Mice treated with the prebiotic oligofructose showed improved intestinal homeostasis as indicated by increased intectin.


Special Research Units


Petrodromus