Amino acid synthesis

Amino acid synthesis is the set of biochemical processes (metabolic pathways) by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can only synthesize 11 of the 20 standard amino acids (a.k.a. non-essential amino acid), and in time of accelerated growth, histidine can be considered an essential amino acid.
From intermediates of the citric acid cycle and other pathways.
Of the basic set of twenty amino acids (not counting selenocysteine), humans cannot synthesize eight. In addition, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered conditionally essential, meaning they are not normally required in the diet but must be supplied exogenously to specific populations that do not synthesize it in adequate amounts. For example, enough arginine is synthesized by the urea cycle to meet the needs of an adult but perhaps not those of a growing child. Amino acids that must be obtained from the diet are called essential amino acids. Nonessential amino acids are produced in the body. The pathways for the synthesis of nonessential amino acids are quite simple. Glutamate dehydrogenase catalyzes the reductive amination of α-ketoglutarate to glutamate. A transamination reaction takes place in the synthesis of most amino acids. At this step, the chirality of the amino acid is established. Alanine and aspartate are synthesized by the transamination of pyruvate and oxaloacetate, respectively. Glutamine is synthesized from NH4+ and glutamate, and asparagine is synthesized similarly. Proline and arginine are derived from glutamate. Serine, formed from 3-phosphoglycerate, is the precursor of glycine and cysteine. Tyrosine is synthesized by the hydroxylation of phenylalanine, an essential amino acid. The pathways for the biosynthesis of essential amino acids are much more complex than those for the nonessential ones.
Cortisol inhibits protein synthesis.
α-Ketoglutarates: glutamate, glutamine, proline, arginine.
Most amino acids are synthesized from α-ketoacids, and later transaminated from another amino acid, usually glutamate. The enzyme involved in this reaction is an aminotransferase.
Glutamate itself is formed by amination of α-ketoglutarate:
The α-ketoglutarate family of amino acid synthesis (synthesis of glutamate, glutamine, proline and arginine) begins with α-ketoglutarate, an intermediate in the Citric Acid Cycle. The concentration of α-ketoglutarate is dependent on the activity and metabolism within the cell along with the regulation of enzymatic activity. In "E. coli" citrate synthase, the enzyme involved in the condensation reaction initiating the Citric Acid Cycle is strongly inhibited by α-ketoglutarate feedback inhibition and can be inhibited by DPNH as well high concentrations of ATP. This is one of the initial regulations of the α-ketoglutarate family of amino acid synthesis.
The regulation of the synthesis of glutamate from α-ketoglutarate is subject to regulatory control of the Citric Acid Cycle as well as mass action dependent on the concentrations of reactants involved due to the reversible nature of the transamination and glutamate dehydrogenase reactions.
The conversion of glutamate to glutamine is regulated by glutamine synthetase (GS) and is a key step in nitrogen metabolism. This enzyme is regulated by at least four different mechanisms: 1. Repression and depression due to nitrogen levels; 2. Activation and inactivation due to enzymatic forms (taut and relaxed); 3. Cumulative feedback inhibition through end product metabolites; and 4. Alterations of the enzyme due to adenylation and deadenylation. In rich nitrogenous media or growth conditions containing high quantities of ammonia there is a low level of GS, whereas in limiting quantities of ammonia the specific activity of the enzyme is 20-fold higher. The confirmation of the enzyme plays a role in regulation depending on if GS is in the taut or relaxed form. The taut form of GS is fully active but, the removal of manganese converts the enzyme to the relaxed state. The specific conformational state occurs based on the binding of specific divalent cations and is also related to adenylation. The feedback inhibition of GS is due to a cumulative feedback due to several metabolites including L-tryptophan, L-histidine, AMP, CTP, glucosamine-6-phosphate and carbamyl phosphate, alanine, and glycine. An excess of any one product does not individually inhibit the enzyme but a combination or accumulation of all the end products have a strong inhibitory effect on the synthesis of glutamine. Glutamine synthase activity is also inhibited via adenylation. The adenylation activity is catalyzed by the bifunctional adenylyltransferase/adenylyl removal (AT/AR) enzyme. Glutamine and a regulatory protein called PII act together to stimulate adenylation.
The regulation of proline biosynthesis can depend on the initial controlling step through negative feedback inhibition. In "E. coli", proline allosterically inhibits Glutamate 5-kinase which catalyzes the reaction from L-glutamate to an unstable intermediate L-γ-Glutamyl phosphate.
Arginine synthesis also utilizes negative feedback as well as repression through a repressor encoded by the gene "argR". The gene product of "argR", ArgR an aporepressor, and arginine as a corepressor affect the operon of arginine biosynthesis. The degree of repression is determined by the concentrations of the repressor protein and corepressor level.
Erythrose 4-phosphate and phosphoenolpyruvate: phenylalanine, tyrosine, and tryptophan.
Phenylalanine, tyrosine, and tryptophan, the aromatic amino acids, arise from chorismate. The first step, condensation of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) from PEP/E4P, uses three isoenzymes AroF, AroG, and AroH. Each one of these has its synthesis regulated from tyrosine, phenylalanine, and tryptophan, respectively. The rest of the enzymes in the common pathway (conversion of DAHP to chorismate) appear to be synthesized constitutively, except for shikimate kinase, which can be inhibited by shikimate through linear mixed-type inhibition.
Tyrosine and phenylalanine are biosynthesized from prephenate, which is converted to an amino acid-specific intermediate. This process is mediated by a phenylalanine (PheA) or tyrosine (TyrA) specific chorismate mutase-prephenate dehydrogenase. PheA uses a simple dehydrogenase to convert prephenate to phenylpyruvate, while TyrA uses a NAD-dependent dehydrogenase to make 4-hydroxylphenylpyruvate. Both PheA and TyrA are feedback inhibited by their respective amino acids. Tyrosine can also be inhibited at the transcriptional level by the TyrR repressor. TyrR binds to the TyrR boxes on the operon near the promoter of the gene that it wants to repress.
Tryptophan biosynthesis involves conversion of chorismate to anthranilate using anthranilate synthase. This enzyme requires either glutamine as the amino group donor or ammonia itself. Anthranilate synthase is regulated by the gene products of trpE and trpG. trpE encodes the first subunit, which binds to chorismate and moves the amino group from the donor to chorismate. trpG encodes the second subunit, which facilitates the transfer of the amino group from glutamine. Anthranilate synthase is also regulated by feedback inhibition: tryptophan is a co-repressor to the TrpR repressor.
Oxaloacetate/aspartate: lysine, asparagine, methionine, threonine, and isoleucine.
The oxaloacetate/aspartate family of amino acids is composed of lysine, asparagine, methionine, threonine, and isoleucine. Aspartate can be converted into lysine, asparagine, methionine and threonine. Threonine also gives rise to isoleucine. The associated enzymes are subject to regulation via feedback inhibition and/or repression at the genetic level. As is typical in highly branched metabolic pathways, additional regulation at each branch point of the pathway. This type of regulatory scheme allows control over the total flux of the aspartate pathway in addition to the total flux of individual amino acids. The aspartate pathway uses L-aspartic acid as the precursor for the biosynthesis of one fourth of the building block amino acids.
Aspartate.
The biosynthesis of aspartate frequently involves the transamination of oxaloacetate.
The enzyme aspartokinase, which catalyzes the phosphorylation of aspartate and initiates its conversion into other amino acids, can be broken up into 3 isozymes, AK-I, II and III. AK-I is feed-back inhibited by threonine, while AK-II and III are inhibited by lysine. As a sidenote, AK-III catalyzes the phosphorylation of aspartic acid that is the committed step in this biosynthetic pathway. Aspartate kinase becomes downregulated by the presence of threonine or lysine.
Lysine.
Lysine is synthesized from aspartate via the diaminopimelate (DAP) pathway. The initial two stages of the DAP pathway are catalyzed by aspartokinase and aspartate semialdehyde dehydrogenase. These enzymes play a key role in the biosynthesis of lysine, threonine, and methionine. There are two bifunctional aspartokinase/homoserine dehydrogenases, ThrA and MetL, in addition to a monofunctional aspartokinase, LysC. Transcription of aspartokinase genes is regulated by concentrations of the subsequently produced amino acids, lysine, threonine, and methionine. The higher these amino acids concentrations, the less the gene is transcribed. ThrA and LysC are also feed-back inhibited by threonine and lysine. Finally, DAP decarboxylase LysA mediates the last step of the lysine synthesis and is common for all studied bacterial species. The formation of aspartate kinase (AK), which catalyzes the phosphorylation of aspartate and initiates its conversion into other amino acids, is also inhibited by both lysine and threonine, which prevents the formation of the amino acids derived from aspartate. Additionally, high lysine concentrations inhibit the activity of dihydrodipicolinate synthase (DHPS). So, in addition to inhibiting the first enzyme of the aspartate families biosynthetic pathway, lysine also inhibits the activity of the first enzyme after the branch point, i.e. the enzyme that is specific for lysine's own synthesis.
Asparagine.
The biosynthesis of asparagine originates with aspartate using a transaminase enzyme. The enzyme asparagine synthetase produces asparagine, AMP, glutamate, and pyrophosphate from aspartate, glutamine, and ATP. In the asparagine synthetase reaction, ATP is used to activate aspartate, forming β-aspartyl-AMP. Glutamine donates an ammonium group, which reacts with β-aspartyl-AMP to form asparagine and free AMP.
Two asparagine synthetases are found in bacteria. Both are referred to as the AsnC protein. They are coded for by the genes AsnA and AsnB. AsnC is autogenously regulated, which is where the product of a structural gene regulates the expression of the operon in which the genes reside. The stimulating effect of AsnC on AsnA transcription is downregulated by asparagine. However, the autoregulation of AsnC is not affected by asparagine.
Methionine.
Biosysnthesis by the transsulfuration pathway starts with aspartic acid. Relevant enzymes include aspartokinase, aspartate-semialdehyde dehydrogenase, homoserine dehydrogenase, homoserine O-transsuccinylase, cystathionine-γ-synthase, Cystathionine-β-lyase (in mammals, this step is performed by homocysteine methyltransferase or betaine—homocysteine S-methyltransferase.)
Methionine biosynthesis is subject to tight regulation. The repressor protein MetJ, in cooperation with the corepressor protein S-adenosyl-methionine, mediates the repression of methionine's biosynthesis. The regulator MetR is required for MetE and MetH gene expression and functions as a transactivator of transcription for these genes. MetR transcriptional activity is regulated by homocystein, which is the metabolic precursor of methionine. It is also known that vitamin B12 can repress MetE gene expression, which is mediated by the MetH holoenzyme.
Threonine.
In plants and microorganisms, threonine is synthesized from aspartic acid via α-aspartyl-semialdehyde and homoserine. Homoserine undergoes "O"-phosphorylation; this phosphate ester undergoes hydrolysis concomitant with relocation of the OH group. Enzymes involved in a typical biosynthesis of threonine include aspartokinase, β-aspartate semialdehyde dehydrogenase, homoserine dehydrogenase, homoserine kinase, threonine synthase.
The biosynthesis of threonine is regulated via allosteric regulation of its precursor, homoserine, by structurally altering the enzyme homoserine dehydrogenase. This reaction occurs at a key branch point in the pathway, with the substrate homoserine serving as the precursor for the biosynthesis of lysine, methionine, threonin and isoleucine. High levels of threonine result in low levels of homoserine synthesis. The synthesis of aspartate kinase (AK), which catalyzes the phosphorylation of aspartate and initiates its conversion into other amino acids, is feed-back inhibited by lysine, isoleucine, and threonine, which prevents the synthesis of the amino acids derived from aspartate. So, in addition to inhibiting the first enzyme of the aspartate families biosynthetic pathway, threonine also inhibits the activity of the first enzyme after the branch point, i.e. the enzyme that is specific for threonine's own synthesis.
Isoleucine.
In plants and microorganisms, isoleucine is biosynthesized from pyruvic acid and alpha-ketoglutarate. Enzymes involved in this biosynthesis include acetolactate synthase (also known as acetohydroxy acid synthase), acetohydroxy acid isomeroreductase, dihydroxyacid dehydratase, and Valine aminotransferase.
In terms of regulation, the enzymes threonine deaminase, dihydroxy acid dehydrase, and transaminase are controlled by end-product regulation. i.e. the presence of isoleucine will downregulate threonine biosynthesis. High concentrations of isoleucine also result in the downregulation of aspartate's conversion into the aspartyl-phosphate intermediate, hence halting further biosynthesis of lysine, methionine, threonine, and isoleucine.
Ribose 5-phosphates: histidine.
The synthesis of histidine in "E. coli" is a complex pathway involving several enzymes. Synthesis begins with phosphorylation of 5-phosphoribosyl-pyrophosphate (PRPP), catalyzed by ATP-phosphoribosyl transferase. Phosphoribosyl-ATP converts to phosphoribosyl-AMP (PRAMP). His4 then catalyzes the formation of phosphoribosylformiminoAICAR-phosphate, which is then converted to phosphoribulosylformimino-AICAR-P by the His6 gene product. His7 splits phosphoribulosylformimino-AICAR-P to form -erythro-imidazole-glycerol-phosphate. After, His3 forms imidazole acetol-phosphate releasing water. His5 then makes -histidinol-phosphate, which is then hydrolyzed by His2 making histidinol. His4 catalyzes the oxidation of -histidinol to form -histidinal, an amino aldehyde. In the last step, -histidinal is converted to -histidine.
In general, the histidine biosynthesis is very similar in plants and microorganisms.
HisG → HisE/HisI → HisA → HisH → HisF → HisB → HisC → HisB → HisD (HisE/I and HisB are both bifunctional enzymes)
The enzymes are coded for on the his operon. This operon has a distinct block of the leader sequence, called block 1:
Met-Thr-Arg-Val-Gln-Phe-Lys-His-His-His-His-His-His-His-Pro-Asp
This leader sequence is important for the regulation of histidine in "E. coli". The "his" operon operates under a system of coordinated regulation where all the gene products will be repressed or depressed equally. The main factor in the repression or derepression of histidine synthesis is the concentration of histidine charged tRNAs. The regulation of histidine is actually quite simple considering the complexity of its biosynthesis pathway and, it closely resembles regulation of tryptophan. In this system the full leader sequence has 4 blocks of complementary strands that can form hairpin loops structures. Block one, shown above, is the key to regulation. When histidine charged tRNA levels are low in the cell the ribosome will stall at the string of His residues in block 1. This stalling of the ribosome will allow complementary strands 2 and 3 to form a hairpin loop. The loop formed by strands 2 and 3 forms an anti-terminator and translation of the "his" genes will continue and histidine will be produced. However, when histidine charged tRNA levels are high the ribosome will not stall at block 1, this will not allow strands 2 and 3 to form a hairpin. Instead strands 3 and 4 will form a hairpin loop further downstream of the ribosome. The hairpin loop formed by strands 3 and 4 is a terminating loop, when the ribosome comes into contact with the loop, it will be “knocked off” the transcript. When the ribosome is removed the "his" genes will not be translated and histidine will not be produced by the cell.
3-Phosphoglycerates: serine, glycine, cysteine.
Serine.
Serine is the first amino acid in this family to be produced; it is then modified to produce both glycine and cysteine (and many other biologically important molecules). Serine is formed from 3-phosphoglycerate in the following pathway:
3-phosphoglycerate → phosphohydroxyl-pyruvate → phosphoserine → serine
The conversion from 3-phosphoglycerate to phosphohydroxyl-pyruvate is achieved by the enzyme phosphoglycerate dehydrogenase. This enzyme is the key regulatory step in this pathway. Phosphoglycerate dehydrogenase is regulated by the concentration of serine in the cell. At high concentrations this enzyme will be inactive and serine will not be produced. At low concentrations of serine the enzyme will be fully active and serine will be produced by the bacterium. Since serine is the first amino acid produced in this family both glycine and cysteine will be regulated by the available concentration of serine in the cell.
Glycine.
Glycine is biosynthesized from serine, catalyzed by serine hydroxymethyltransferase (SHMT). The enzyme effectively replaces a hydroxymethyl group with a hydrogen atom.
SHMT is coded by the gene "glyA". The regulation of "glyA" is complex and is known to incorporate serine, glycine, methionine, purines, thymine, and folates, The full mechanism has yet to be elucidated. The methionine gene product MetR and the methionine intermediate homocysteine are known to positively regulate glyA. Homocysteine is a coactivator of "glyA" and must act in concert with MetR. On the other hand, PurR, a protein which plays a role in purine synthesis and S-adeno-sylmethionine are known to down regulate "glyA". PurR binds directly to the control region of "glyA" and effectively turns the gene off so that glycine will not be produced by the bacterium.
Cysteine.
The genes required for the synthesis of cysteine are coded for on the "cys" regulon. The integration of sulfur is positively regulated by CysB. Effective inducers of this regulon are N-acetyl-serine (NAS) and very small amounts of reduced sulfur. CysB functions by binding to DNA half sites on the "cys" regulon. These half sites differ in quantity and arrangement depending on the promoter of interest. There is however one half site that is conserved. It lies just upstream of the -35 site of the promoter. There are also multiple accessory sites depending on the promoter. In the absence of the inducer, NAS, CysB will bind the DNA and cover many of the accessory half sites. Without the accessory half sites the regulon cannot be transcribed and cysteine will not be produced. It is believed that the presence of NAS causes CysB to undergo a conformational change. This conformational change allows CysB to bind properly to all the half sites and causes the recruitment of the RNA polymerase. The RNA polymerase will then transcribe the "cys" regulon and cysteine will be produced.
Further regulation is required for this pathway, however. CysB can down regulate its own transcription by binding to its own DNA sequence and blocking the RNA polymerase. In this case NAS will act to disallow the binding of CysB to its own DNA sequence. OAS is a precursor of NAS, cysteine itself can inhibit CysE which functions to create OAS. Without the necessary OAS, NAS will not be produced and cysteine will not be produced. There are two other negative regulators of cysteine. These are the molecules sulfide and thiosulfate, they act to bind to CysB and they compete with NAS for the binding of CysB.
Pyruvate: alanine, valine, and leucine.
Pyruvate, the end result of glycolysis, can feed into both the TCA cycle and fermentation processes. Reactions beginning with either one or two molecules of pyruvate lead to the synthesis of alanine, valine, and leucine. Feedback inhibition of final products is the main method of inhibition, and, in "E. coli", the "ilvEDA" operon also plays a part in this regulation.
Alanine.
Alanine is produced by the transamination of one molecule of pyruvate using two alternate steps: 1) conversion of glutamate to α-ketoglutarate using a glutamate-alanine transaminase, and 2) conversion of valine to α-ketoisovalerate via Transaminase C.
Not much is known about the regulation of alanine synthesis. The only definite method is the bacterium's ability to repress Transaminase C activity by either valine or leucine (see "ilvEDA" operon). Other than that, alanine biosynthesis does not seem to be regulated.
Valine.
Valine is produced by a four-enzyme pathway. It begins with the condensation of two equivalents of pyruvate catalyzed by acetohydroxy acid synthase yielding α-acetolactate. The second step involves the NADPH+-dependent reduction of α-acetolactate and migration of methyl groups to produce α, β-dihydroxyisovalerate. This is catalyzed by acetohydroxy isomeroreductase. The third step is the dehydration of α, β-dihydroxyisovalerate catalyzed by dihydroxy acid dehydrase. In the fourth and final step, the resulting α-ketoisovalerate undergoes transamination catalyzed either by an alanine-valine transaminase or a glutamate-valine transaminase. Valine biosynthesis is subject to feedback inhibition in the production of acetohydroxy acid synthase.
Leucine.
The leucine synthesis pathway diverges from the valine pathway beginning with α-ketoisovalerate. α-Isopropylmalate synthase catalyzes this condensation with acetyl CoA to produce α-isopropylmalate. An isomerase converts α-isopropylmalate to β-isopropylmalate. The third step is the NAD+-dependent oxidation of β-isopropylmalate catalyzed by a dehydrogenase. The final step is the transamination of the α-ketoisocaproate by the action of a glutamate-leucine transaminase.
Leucine, like valine, regulates the first step of its pathway by inhibiting the action of the α-Isopropylmalate synthase. Because leucine is synthesized by a diversion from the valine synthetic pathway, the feedback inhibition of valine on its pathway also can inhibit the synthesis of leucine.
ilvEDA operon.
The genes that encode both the dihydroxy acid dehydrase used in the creation of α-ketoisovalerate and Transaminase E, as well as other enzymes are encoded on the ilvEDA operon. This operon is bound and inactivated by valine, leucine, and isoleucine. (Isoleucine is not a direct derivative of pyruvate, but is produced by the use of many of the same enzymes used to produce valine and, indirectly, leucine.) When one of these amino acids is limited, the gene furthest from the amino-acid binding site of this operon can be transcribed. When a second of these amino acids is limited, the next-closest gene to the binding site can be transcribed, and so forth.
Commercial syntheses of amino acids.
The commercial production of amino acids usually relies on mutant bacteria that overproduce individual amino acids using glucose as a carbon source. Some amino acids are produced by enzymatic conversions of synthetic intermediates. 2-Aminothiazoline-4-carboxylic acid is an intermediate in the industrial synthesis of L-cysteine for example. Aspartic acid is produced by the addition of ammonia to fumarate using a lyase.


Psychrobacter

Psychrobacter is a genus of Gram-negative, osmotolerant, oxidase-positive, psychrophilic or psychrotolerant, aerobic bacteria which belong to the family Moraxellaceae and the class Gammaproteobacteria. The shape is typically cocci or coccobacilli. Some of those bacteria were isolated from humans and can cause humans infections such as endocarditis and peritonitis. This genus of bacteria is able to grow at temperatures between −10 and 42 °C. Rudi Rossau found through DNA-rRNA hybridization analysis that "Psychrobacter" belongs to the Moraxellaceae. The first species ("Psychrobacter immobilis") was described by Juni and Heym. "Psychrobacter" occur in wide range of moist, cold saline habitats, but they also occur in warm and slightly saline habitats.
Hypoacylated lipopolysaccharide (LPS) isolated from "Psychrobacter cryohalolentis" and "Psychrobacter arcticus" induces moderate TLR4-mediated inflammatory response in macrophages and such LPS bioactivity may potentially result in the failure of local and systemic bacterial clearance in patients.
Species include:


Thomas L. Morris


Inhuman Royal Family


Non-mevalonate pathway

The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-"C"-methyl--erythritol 4-phosphate/1-deoxy--xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The currently preferred name for this pathway is the MEP pathway, since MEP is the first committed metabolite on the route to IPP.
Isoprenoid precursor biosynthesis.
The classical mevalonate pathway or HMG-CoA reductase pathway is a metabolic pathway from the biosynthesis of isoprenoid precursors present in most higher eukaryotes and some bacteria. It is important for the production of IPP and DMAPP, which serve as the basis for the biosynthesis of isoprenoid (terpenoid) molecules used in processes as diverse as protein prenylation, cell membrane maintenance, the synthesis of hormones, protein anchoring and "N"-glycosylation.
Bacteria, plants, and apicomplexan protozoa—such as malaria parasites—are able to produce isoprenoid precursors using an alternative pathway, the MEP pathway, which is a "non-mevalonate pathway." In the case of plants and certain protozoa, the biosynthesis of IPP/DMAPP takes place in plastid organelles. Plants synthesise isoprenoid precursors using the mevalonate pathway in the cytoplasm and using the MEP pathway in their chloroplasts. Bacteria such as the model organism "Escherichia coli" have been engineered for co-expressing both the MEP and the mevalonate pathway. Distribution of the metabolic fluxes between the MEP and the mevalonate pathway can be studied using 13C-glucose isotopomers. Bacteria that use the MEP pathway include important pathogens such "Mycobacterium tuberculosis".
Reactions.
The reactions of the non-mevalonate pathway are as follows, taken primarily from Eisenreich and co-workers, except where the bold labels are additional local abbreviations to assist in connecting the table to the scheme above:
Inhibition and other pathway research.
DXP reductoisomerase (also known as: DXR, DOXP reductoisomerase, IspC, MEP synthase), is a key enzyme in the MEP pathway. It can be inhibited by the natural product
fosmidomycin, which is under study as a starting point to develop a candidate antibacterial or antimalarial drug.
The intermediate, HMB-PP, is a natural activator of human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood, and cells that "play a crucial role in the immune response to microbial pathogens".


Leslie Ying

Leslie Ying is an American biomedical engineering scientist in the field of medical imaging. She is the Clifford C. Furnas Professor of Biomedical Engineering and Electrical Engineering at University at Buffalo, The State University of New York. Ying is the Editor-in-Chief of IEEE Transactions on Medical Imaging and is also an American Institute for Medical and Biological Engineering (AIMBE) Fellow.
Education.
Ying graduated with her bachelor's degree in electrical engineering at Tsinghua University in 1997. In 1999 and 2003, respectively, she graduated with her master's degree and Doctorate of Philosophy from the University of Illinois at Urbana-Champaign.
Career.
From 2003 to 2011, Ying was an assistant and then associate professor of electrical engineering and computer science at the University of Wisconsin–Milwaukee. She joined the University at Buffalo, the State University of New York in Spring 2012 as a professor in the departments of biomedical engineering and electrical engineering. She was named the Clifford C. Furnas Professor of Electrical and Biomedical Engineering in September of 2019.
Research interests.
Ying heads the Computational Biomedical Imaging Laboratory (CBIL) and her research interests center around magnetic resonance imaging. She is specifically interested in image reconstruction, compressed sensing, and machine learning. Her current work involves using parallel magnetic resonance imaging using multichannel receiver coils, sparsity / compressed sensing signal recovery, and super-resolution microscopy. She has published three open source Matlab code libraries: two-dimensional phase unwrapping, joint estimation of coil sensitivities and image in parallel imaging (JSENSE) packages, and Nonlinear GRAPPA: a kernel approach to parallel MRI reconstruction.
Professional Activities.
Since 2019, Ying has served as Editor-in-Chief of "IEEE Transactions on Medical Imaging". She has also been an associate editor for the IEEE Annual International Conference of Engineering in Medicine and Biology Society since 2008 and for the IEEE International Symposium on Biomedical Imaging since 2013. Ying previously served as deputy editor for Magnetic Resonance in Medicine from 2012 to 2019 and as an associate editor for IEEE Transactions on Biomedical Engineering from 2009 to 2012. She was an editorial board member for Scientific Reports by Nature Research from 2016 to 2019 and for Magnetic Resonance in Medicine in 2012. She was a member of the IEEE Engineering in Medicine and Biology Society administrative committee from 2013 to 2015 and of the technical program committees for the IEEE Engineering in Medicine and Biology Society Annual Conference in 2014 and the IEEE International Symposium on Biomedical Imaging in 2011.


Michael W. Berns

Michael W. Berns (born December 1, 1942) is a professor of surgery and cell biology at the University of California, Irvine (UCI) and the University of California, San Diego. Berns is a founder of the first Laser Microbeam Program (LAMP), the Beckman Laser Institute, the UCI Center for Biomedical Engineering, and the UCI Photonics Incubator.
His pioneering work has focused on the use of laser technology in medical and biological research. He has developed tools and techniques for the surgical use of lasers, down to the level of manipulating single cells and individual chromosomes. Berns has published extensively on use of lasers in both biomedical research and medical treatment of illnesses including skin disorders, vascular disease, eye problems, and cancer.
Education.
Berns received his B.S. from Cornell University, Ithaca, NY in 1964, followed by his M.S. in 1966 and his Ph.D. in 1968. From 1968 to 1970, he held a postdoctoral position at the Pasadena Foundation for Medical Research, Pasadena, California.
Career.
Berns was an assistant professor in the department of zoology of the University of Michigan, Ann Arbor from 1970 to 1972. He them joined the University of California, Irvine (UCI) as an associate professor and department chair in the Department of Developmental and Cell Biology. He was named the Arnold and Mabel Beckman Professor in 1988.
In addition to a number of appointments at the University of California, Irvine, he became an adjunct professor in the Department of Biomedical Engineering at the University of California, San Diego in 2000.
Berns founded the first Laser Microbeam Program (LAMP) at UCI in 1979.
Sponsored by the National Institutes of Health (NIH) as a National Biotechnology Resource, the LAMP center's sophisticated laser microsurgery instruments could be used by cell biologists from across the country.
Berns co-founded the Beckman Laser Institute at UCI in 1982, with support from Arnold Beckman. The nonprofit institute for translational research opened on June 4, 1986. Berns was its first director, serving from 1982 to 2003.
Berns was also a founding director of the UCI Center for Biomedical Engineering, from 1999 to 2000, and founded the UCI Photonics Incubator in 1999.
Research.
In 2006, Berns received the Biomedical Optics Lifetime Achievement Award at SPIE's International Symposium on Biomedical Optics, “for his contributions to the development and growth of laser microbeam technology, a major step towards establishing new tools for understanding laser interactions with biological tissues, which have resulted in significant improvements in diagnosis and treatment of disease.” Sometimes referred to as the "father of laser microbeams," Berns has written over 480 articles and 6 books.
In 1969, Berns published a generative paper on use of lasers for subcellular surgery in "Nature". Using an argon laser with a phase-contrast microscope, small lesions were placed at specifically chosen sites on the chromosomes of cells sensitized with chemical fluorophores.
In subsequent research, Berns and others found that could be used to cut organelles such as mitochondria or stress fibers without prior sensitization. This landmark study concluded that focusable laser light could have wide application to the ablation of cell components in biological systems. When combined with a light microscope to display the structures in a living cell, lasers could be used to selectively target those structures with minimum damage to surrounding structures.
Since then Berns has investigated the basic interactions of light beams at the levels of tissues, cells, and molecules. He has developed tools and techniques such as "laser scissors" and "laser tweezers" for manipulation of structures within a living cell, that can be used for the examination of cell biology and treatment of molecular pathology.
Awards and honors.
Honors and awards include the following:


Spin column-based nucleic acid purification

Spin column-based nucleic acid purification is a solid phase extraction method to quickly purify nucleic acids. This method relies on the fact that nucleic acid will bind to the solid phase of silica under certain conditions.
Procedure.
The stages of the method are lyse, bind, wash, and elute. More specifically, this entails the lysis of target cells to release nucleic acids, selective binding of nucleic acid to a silica membrane, washing away particulates and inhibitors that are not bound to the silica membrane, and elution of the nucleic acid, with the end result being purified nucleic acid in an aqueous solution.
For lysis, the cells (blood, tissue, etc.) of the sample must undergo a treatment to break the cell membrane and free the nucleic acid. Depending on the target material, this can include the use of detergent or other buffers, proteinases or other enzymes, heating to various times/temperatures, or mechanical disruption such as cutting with a knife or homogenizer, using a mortar and pestle, or bead-beating with a bead mill.
For binding, a buffer solution is then added to the lysed sample along with ethanol or isopropanol. The sample in binding solution is then transferred to a spin column, and the column is put either in a centrifuge or attached to a vacuum. The centrifuge/vacuum forces the solution through a silica membrane that is inside the spin column, where under the right ionic conditions, nucleic acids will bind to the silica membrane, as the rest of the solution passes through. With the target material bound, the flow-through can be removed.
To wash, a new buffer is added onto the column, then centrifuged/vacuumed through the membrane. This buffer is intended to maintain binding conditions, while removing the binding salts and other remaining contaminants. Generally it takes several washes, often with increasing percentages of ethanol/isopropanol, until the nucleic acid on the silica membrane is free of contaminants. The last 'wash' is often a dry step to allow the alcohol to evaporate, leaving only purified nucleic acids bound to the column.
Finally, elution is the process of adding an aqueous solution to the column, allowing the hydrophilic nucleic acid to leave the column and return to solution. This step may be improved with salt, pH, time, or heat. Finally, to capture the eluate/eluent, the column is transferred into a clean microtube prior to a last centrifugation step.
Related methods.
Even prior to the nucleic acid methods employed today, it was known that in the presence of chaotropic agents, such as sodium iodide or sodium perchlorate, DNA binds to silica, glass particles or to unicellular algae called diatoms which shield their cell walls with silica. This property was used to purify nucleic acid using glass powder or silica beads under alkaline conditions. This was later improved using guanidinium thiocyanate or guanidinium hydrochloride as the chaotropic agent. For ease of handling, the use of glass beads was later changed to silica columns. And to enable use of automated extraction instruments, there was development of silica-coated paramagnetic beads, more commonly referred to as "magnetic bead" extraction.


Marzyeh Ghassemi

Marzyeh Ghassemi is a Canada-based researcher in the field of computational medicine, where her research focuses on developing machine-learning algorithms to inform health-care decisions. She is currently an assistant professor at the University of Toronto's Department of Computer Science and Faculty of Medicine, and is a Canada CIFAR Artificial Intelligence (AI) chair and Canada Research Chair (Tier Two) in machine learning for health.
Research career.
Ghassemi pursued a bachelors of science degree in computer science and electrical engineering at New Mexico State University, a master's degree in biomedical engineering from Oxford University, and a PhD at the Massachusetts Institute of Technology (MIT).
In 2012, Ghassemi was a member of the Sana AudioPulse team, who won the GSMA Mobile Health Challenge as a result of developing a mobile phone app to screen for hearing impairment remotely.
During her PhD, Ghassemi collaborated with doctors based within Beth Israel Deaconess Medical Center's intensive care unit and noted the extensive amount of clinical data available. She then developed machine-learning algorithms to take in diverse clinical inputs and predict risks and mortality, such as the length of the patient's stay within the hospital, and whether additional interventions (such as blood transfusions) are necessary. In addition, Ghassemi was also the lead PhD student in a study where accelerometer data collected from smart wearable devices to successfully detect differences between patients with muscle tension dysphonia (MTD) and those without MTD.
Upon completing her PhD, Ghassemi was affiliated with both Alphabet’s Verily (as a visiting researcher) and at MIT (as a part-time post-doctoral researcher in Peter Szolovits' Computer Science and Artificial Intelligence Lab).
Ghassemi then joined as an assistant professor at the University of Toronto in fall 2018, where she is co-appointed to the Department of Computer Science and the University of Toronto's Faculty of Medicine, making her the first joint hire in computational medicine for the university. Ghassemi's lab is titled the Machine Learning for Health (ML4H) lab.
Ghassemi is also a faculty member at the Vector Institute. She currently holds the Canada CIFAR Artificial Intelligence (AI) Chair position. In June 2019, Ghassemi was appointed a Canada Research Chair (Tier Two) in machine learning for health. Ghassemi has been cited over 1900 times, and has an h-index and i-10 index of 23 and 36 respectively. She was named as one of the 35 Innovators Under 35, in the visionaries category, in MIT Technology Review’s annual list.


LdcC RNA motif

The "ldcC" RNA motif is a conserved RNA structure that was discovered by bioinformatics.
"ldcC" motif RNAs are found in Firmicutes and two species of Spirochaetes.
"ldcC" motif RNAs likely function as cis-regulatory elements, in view of their positions upstream of protein-coding genes. The genes presumably regulated by "ldcC" RNAs are decarboxylases of arginine, ornithine, S-adenosylmethionine or other substrates. Endopeptidase C39A and "potA" (a transporter of spermidine/putrescine) is also relatively common. Thus, "ldcC" RNAs could regulate polyamine metabolism.
The "ldcC" motif might have a pseudoknot in its secondary structure, but it is unclear.


Andrew Laine

Andrew F. Laine is an American biomedical engineer, currently the Percy K. and Vida L. W. Hudson Professor at Columbia University and is an Institute of Electrical and Electronics Engineers Fellow.


3-MeO-PCMo

3-MeO-PCMo is a dissociative anesthetic drug which is similar in structure to phencyclidine and been sold online as a designer drug. The inhibitory effect of 3-MeO-PCMo on the reduction in the density of the drebrin clusters by NMDAR stimulation with glutamic acid is lower than that of PCP or 3-MeO-PCP, with half maximal inhibitory concentration (IC50) values of 26.67 μM (3-MeO-PCMo), 2.02 μM (PCP) and 1.51 μM (3-MeO-PCP).


Charles Caesar

Sir Charles Caesar (27 January 1590 – 6 December 1642), of Benington in Hertfordshire, was an English judge who served as Master of the Rolls in the period leading up to the outbreak of the English Civil War; his father Sir Julius Caesar had held the same office for many years.
Caesar entered Magdalen College, Oxford, aged 12 in 1602, and was a fellow of All Souls from 1605 to 1611. He was incorporated at Cambridge with a LL.B. in 1609, but continued at Oxford, where he was made Doctor of Civil and Canon Law in 1612. In 1611 he joined the Middle Temple and began to practice in the ecclesiastical courts; he was knighted in 1613, and served as MP for Weymouth in the Addled Parliament of 1614. In 1615 he was appointed a master in chancery, no doubt through the influence of his father, and continued in this post until 1639; he was also from before 1626 a judge of the Court of Audience and Master of the Faculties, both appointments which held until his death. In 1639 the Mastership of the Rolls became vacant on the death of Sir Dudley Digges, and Caesar consulted Archbishop Laud on whether he might obtain it, but was warned "that as things then stood, the place was not like to go without more money than he thought any wise man would give for it". Caesar, perhaps more ambitious than wise, apparently paid the King £15,000 in a lump sum with a further £2,000 loan, and was duly appointed.
Foss in his "Lives of the Judges" comments that "It is difficult to regret that he did not live long enough to profit by this iniquitous traffic of the judicial seat, as disgraceful to one party as the other". He had made little mark through his tenure of the post when his family was struck down by smallpox in November 1642: one of his daughters died on 2 November, he himself did so on 6 December 1642 (even though, as he declared in the will he made on his death-bed, he had already had the disease as a younger man), and his eldest son, Julius, followed five days later. He was succeeded by his second son, Henry, still a minor at the time of his father's death.


Pygmy shrew tenrec

The pygmy shrew tenrec ("Microgale parvula") is a species of placental mammal in the family Tenrecidae. It is endemic to Madagascar. Its natural habitats are subtropical or tropical moist lowland forests and subtropical or tropical moist montane forests. While it is not endangered, its population is slowly declining as it is threatened by habitat loss. This is of concern, though does not yet merit a higher protection level.
Habitat and Diet.
This tenrec has a far-reaching habitat that stretches from the southern part of the island of Madagascar to the northern peninsula, making it one of the only rodent-like creatures to live in this particular part of the island where species diversity is reduced. It is restricted to intact forest areas for the most part and has an altitude range of between 100 and 1,990 m asl. Like most other tenrecs, the pygmy shrew tenrec is an insectivore, making its diet out of Madagascar's numerous bug and insect species.
History.
The species was catalogued by G. Grandidier in 1934. While the exact parameters of the species and its populations were unknown until the mid 1990s, it was listed as "Endangered" in 1996 when scientists found sufficient data to back up the category. This was recently redacted and changed to "Least Concern" in 2006.
Behavior.
The pygmy shrew tenrec is a nocturnal hunter, using its keen senses of sight and hearing to find and capture prey. While it may also use scent to find the delicious insects it feasts on, this tiny mammal prefers to utilize the night vision evolution has granted it. Shrew tenrecs in general tend to have very large auditory structures and the pygmy shrew tenrec is no different. Large, swiveling ears listen intently for the minute sounds of insects nearby and diminutive but sharp teeth lash out to capture the tasty morsel.
Like most mammals, this tenrec is polygynous, meaning males mate with two or more females. This is to promote successful and plentiful offspring production. It is still unknown whether sexual selection occurs through male on male competition or through female choice, though given its relations' ways of choosing a mate, it can be assumed that it is done through female choice. Now, the question is simply, what makes the females of this species"go wild"?


William Hardy (Australian politician)

William Hardy (died 11 November 1878) was an Australian lawyer and politician.
Hardy was a solicitor and a partner in the prominent Sydney law firm of Stenhouse and Hardy. He was one of Charles Cowper's 21 appointments to the New South Wales Legislative Council in May 1861, but did not take his seat. He subsequently left New South Wales and returned to Ireland. He died from smallpox in 1879 at Booterstown, near Dublin.


MBF Bioscience

MBF Bioscience is a biotech company that develops software and hardware for bioscience research and biomedical application. MBF Bioscience’s main location is Williston, Vermont, USA, but has offices that market, sell, and supports its line of hardware and software products throughout North America, Europe, and Asia.
History.
The company was founded as MicroBrightField,Inc in 1988 by father and son, Dr. Edmund Glaser and Jack Glaser. Their goal was to develop neuroanatomical image software for the research community. To reflect their expanded services, the company changed its name from MicroBrightField, Inc to MBF Bioscience, Inc in 2004. Now, MBF Bioscience provides solutions for stereology, neuron reconstruction, microscopic and whole slide imaging, brain mapping, and worm tracking. The company products are used in a variety of fields including stem cell research, neuroanatomical studies, lung, kidney, reproductive, cardiac and toxicology research.
In 2021, MBF Bioscience acquired Vidrio Technologies. Vidrio Technologies is a provider of software and hardware components for laser scanning and two-photon microscopes based out of Ashburn, Virginia, USA.
Products.
Neurolucida: software for 3D neuron tracing and analysis and 3D brain mapping.
Stereo Investigator is a system designed to conduct unbiased stereology studies.
Neurolucida 360 : software for 3D neuron reconstruction, and somas, varicosities, spines and synapses detection.
Biolucida is an image management system for sharing microscope images online.
WormLab is software that tracks and analyzes and other nematodes.
BrainMaker generates 3D high-resolution reconstructions from serial sections images.
Microlucida is used for image acquisition.
Lucivid is used in the case of retinal stimulation.
Densita allows researchers to analyze autoradiography and optical density.
Vesselucida: software for 3D microvascular tracing and analysis.
Vesselucida 360: Software that is designed for 3D microvascular reconstruction.
ClearScope: Light sheet theta microscope system that is designed to work with cleared tissue specimens.
TissueScope is a whole slide scanner created in collaboration with Huron Digital Pathology.
Vesalius is a resonant scanning laser confocal system that allows 2D and 3D imaging for mounted and cleared tissue specimens.


Mahaletchumy Arujanan

Mahaletchumy Arujanan (born 25 May 1969) is a Malaysian scientist of Malaysian Indian origin. She works as the Global Coordinator of International Service for the Acquisition of Agribiotech Applications (ISAAA) and executive director of Malaysian Biotechnology Information Center (MABIC).
She has a bachelor's degree in biochemistry and microbiology from University Putra Malaysia, a Masters in Biotechnology and a Ph.D. in Science Communication from the University of Malaya. January 2003, she joined MABIC as a project officer and took over as the executive director in May 2005.
She is listed as one of the 100 most influential people in the field of biotechnology by the 7th edition of The Scientific American Worldwide View: A Global Biotechnology Perspective Journal. Arujanan founded the country's first biotechnology newspaper, "The Petri Dish". She is a recipient of 2010 TWAS Regional Prize for Public Understanding of Science for East, Southeast Asia, and Pacific Region, and has been listed as one of the prominent women in biotechnology law and regulations by Biotechnology Law Report. She was recognized as one of the Great Women of Our Time by the Malaysian Women's Weekly in their December 2015 issue.
Early life and education.
Arujanan was born in Klang Valley, Malaysia to a Tamil school headmaster.
Mahaletchumy Arujanan started her primary and secondary education at Convent Klang and continued her pre-university (STPM) at ACS Klang. She pursued her bachelor's degree in University Putra Malaysia, majoring in Microbiology and Biochemistry and graduated in 1993. She continued her Masters in Biotechnology at University of Malaya and graduated in 1997.
Career.
Arujanan started her career as a Technical and Admin Officer with Sandoz Agro Chemicals in 1992. Her stint at Sandoz did not last long as the company merged with Ciba Geigy and the regional office she was working was closed. She joined The International Plant Genetic Resources Institute, now known as Bioversity International as a Programme Officer. She left after 2 years to join the healthcare company DXN. Arujanan left DXN and joined Total Health Concept. 1999 to 2002, Arujanan was struggling to build a career and finally left Total Health Concept in 2002.
She joined the Malaysian Biotechnology Information Centre (MABIC) in January 2003 as a Project Officer and was promoted to be the Executive Director in May 2005. Arujanan revamped MABIC, made efforts to introduce the center to key ministries and government agencies, and forged a strong relationship with international partners. She started engaging with various stakeholders to create awareness on biotechnology. This led her to be a pioneer in science communication in Malaysia. She was appointed the Global Coordinator of ISAAA on 1 May 2019. She is now responsible for the entire network of ISAAA that has its presence in South East Asia, South Asia, East Asia, Africa, USA, and Latin America. Arujanan continued her Ph.D. in science communication in University of Malaya and completed in 2013.
Professional roles.
Arujanan is appointed to a number of committees and advisory panels:
"The Petri Dish".
Arujanan is the founding editor-in-chief for the first science newspaper in Malaysia, "The Petri Dish". The newspaper was initiated to bring biotechnology to the public domain.
The newspaper started as a 12-page monthly in February 2011 with a circulation of 2,000 copies and has grown into a 20-page publication with 6,000 copies circulated to key stakeholders in the fields of science/biotechnology in Malaysia. With a strong belief that science should reach the public, Arujanan made efforts to circulate "The Petri Dish" to shopping malls, private hospitals, Starbucks outlets, and secondary schools. In Feb 2017, Arujanan was creating an online portal for "The Petri Dish".
Contributions.
Society.
Arujanan is an active speaker at schools and community events.


European Journal of Cell Biology

European Journal of Cell Biology is a monthly peer-reviewed scientific journal that was established in 1969 as "Cytobiologie". It is published by Elsevier and the editors-in-chief are Stefan Linder (University Medical Center Hamburg-Eppendorf), Manfred Schliwa (Ludwig Maximilian University of Munich), and Sabine Werner (ETH Zurich). The journal covers research on cell biology. Publishing formats include original research articles, reviews, and short communications.
Abstracting and indexing.
"European Journal of Cell Biology" is abstracted and indexed in:


4-Acetoxy-MET

4-Acetoxy-MET (4-Acetoxy-"N"-methyl-"N"-ethyltryptamine), also known as metacetin or 4-AcO-MET, is a hallucinogenic tryptamine. It is the acetate ester of 4-HO-MET, and a homologue of 4-AcO-DMT. It is a novel compound with very little history of human use. It is sometimes sold as a research chemical by online retailers.
It is expected that the compound is quickly hydrolyzed into the free phenolic 4-HO-MET by serum esterases, but human studies concerning the metabolic fate of this drug are lacking. There is proof that this is a very active substance.
Legality.
4-Acetoxy-MET is unscheduled in the United States.