The other, though, is complicated and not obvious, but mechanistically interesting.
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Chair Yellen has already laid out the Fed's intention to gradually and mechanistically unwind the central bank's balance sheet.
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The wavelengths of the AGWs required to have an effect on the tsunami are so long that it's difficult to imagine them being produced mechanistically at all.
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"We also think that mechanistically it would be difficult to create a significantly longer-lasting Botox because botulinum toxin gradually loses efficacy over four months due to neuronal regeneration," Risinger said.
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Coldplay responded with some of the most mechanistically devastating songs in their repertoire and remained a nose ahead of the competition thanks to the blunt force pairing of Martin's ever-sharpening directness and his band's matching gravitas.
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"Mechanistically it is plausible that there is either a glucose oligomer receptor ... or that it is from enzymatic breakdown within the oral cavity of the glucose polymers into glucose that then gets transported into the sweet-responding taste cells," he said.
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The album's three pieces—one of which stretches over 20 minutes, another over 16—are composed of locomotive guitars, mechanistically programmed electronics (in part provided by techno mad scientist Ricardo Villalobos), and jittery live percussion work, so at least in its component parts, it can seem something like club music.
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Diazomethane also produces ring enlargement, and its reaction is mechanistically similar to the Tiffeneau-Demjanov rearrangement.
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Neuroprotectins A and B, which are bicyclohexapeptides, are to be distinguished structurally and mechanistically from the neuroprotectin D's.
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Some evidence indicates sound production in hardhead catfish is differentiated both mechanistically and contextually. Mechanistically, sound can be produced in different ways. Thin bones by the swim bladder can be vibrated by specialized sonic muscles. Also, grinding of the pharyngeal teeth and rubbing of the pectoral spines against the pectoral girdle can produce sound.
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This model suggests that cause and effect are mechanistically related. In this situation, there is a basic process underlying the cause and effect.
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If occurring in consecutive steps, the intermediate is identical to that which would be generated from an E1cB- elimination reaction. ECH is mechanistically similar to fumarase.
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Mechanistically, the flavin-dependent halogenases are similar to flavin-containing monooxygenases. In the first step, FADH2 is oxidized by molecular oxygen, generating a high- energy flavin hydroperoxide.
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Mechanistically, it appears that multivalent interactions between intrinsically disordered proteins (including cross-beta polymerisation), and/or protein domains that induce oligomeric or polymeric clustering, might play a role in phase separation of proteins.
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Sirtuins that deacetylate histones are structurally and mechanistically distinct from other classes of histone deacetylases (classes I, IIA, IIB and IV), which have a different protein fold and use Zn2+ as a cofactor.
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Functional similarity with group 1 introns and then mechanistically being different from the introns support this hypothesis that VS ribozyme is a chimera formed by insertion of a novel catalytic RNA into group 1 introns.
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Archaea have a single type of RNAP, responsible for the synthesis of all RNA. Archaeal RNAP is structurally and mechanistically similar to bacterial RNAP and eukaryotic nuclear RNAP I-V, and is especially closely structurally and mechanistically related to eukaryotic nuclear RNAP II. The history of the discovery of the archaeal RNA polymerase is quite recent. The first analysis of the RNAP of an archaeon was performed in 1971, when the RNAP from the extreme halophile Halobacterium cutirubrum was isolated and purified. Crystal structures of RNAPs from Sulfolobus solfataricus and Sulfolobus shibatae set the total number of identified archaeal subunits at thirteen.
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Selenoxide elimination (also called α-selenation) is a method for the chemical synthesis of alkenes from selenoxides. It is most commonly used to synthesize α,β-unsaturated carbonyl compounds from the corresponding saturated analogues. It is mechanistically related to the Cope reaction.
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Idealized mechanism for metal- catalysed hydrosilylation of an alkene. Hydrosilylation of alkenes represents a commercially important method for preparing organosilicon compounds. The process is mechanistically similar to the hydrogenation of alkenes. In fact, similar catalysts are sometimes employed for the two catalytic processes.
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Oxidative carbonylation is a class of reactions that use carbon monoxide in combination with an oxidant to generate esters and carbonate esters. These transformations utilize transition metal complexes as homogeneous catalysts. Many of these reactions employ palladium catalysts. Mechanistically, these reactions resemble the Wacker process.
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Mechanistically, the Skeeter syndrome appears to be a particularly intense variant of the ordinary mosquito bite reaction. It involves sequential Type I, III, and IV hypersensitivity reactions that are mediated by the IgE, IgG, and T cells that are directed against mosquito salivary proteins.
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Mechanistically, NCOA2 inhibited Wnt/β-catenin signaling through simultaneously upregulating inhibitors and downregulating stimulators of Wnt/β-catenin pathway. NCOA2 is a novel negative growth regulatory gene repressing the Wnt/β-catenin pathway in CRC, where recurrent fusion with LACTB2 contributes to its disruption.
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In order for paracrine factors to successfully induce a response in the receiving cell, that cell must have the appropriate receptors available on the cell membrane to receive the signals, also known as being competent. Additionally, the responding cell must also have the ability to be mechanistically induced.
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This provides a unique opportunity for the development of AR-specific peptides. Even though small molecule antagonists and NTD antagonist targeting AF2 surface differ in binding sites, they both inhibit AR function by disrupting AF2 function. Therefore, mechanistically, these NTD antagonists may also be classified as ‘AF2 antagonists’.
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Like other lyases, PAL requires only one substrate for the forward reaction, but two for the reverse. It is thought to be mechanistically similar to the related enzyme histidine ammonia-lyase (EC:4.3.1.3, HAL). The systematic name of this enzyme class is L-phenylalanine ammonia-lyase (trans-cinnamate- forming).
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519 Mechanistically, Schopenhauer believed that a person inherits his intellect through his mother, and personal character through the father.On the Suffering of the World (1970), p. 35. Penguin Books – Great Ideas. This belief in heritability of traits informed Schopenhauer's view of love – placing it at the highest level of importance.
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The KYNA made by the GOT2 is thought to be an important factor in brain pathology. It is suggested that KYNA synthesized by GOT2 could constitute a common, and mechanistically relevant, feature of the neurotoxicity caused by mitochondrial poisons, such as rotenone, malonate, 1-methyl-4-phenylpyridinium, and 3-nitropropionic acid.
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Mechanistically, CTCF may function as a boundary element to stop the spread of DNA methylation. Results from experiments conducted by Soto- Reyes et al. indicate a negative effect of methylation on the function and expression of miR-125b1. Therefore, they concluded that DNA methylation has a part in silencing the gene.
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Bacon emphasizes that grammatical rules cannot be applied mechanistically but must be understood as a structure through which to attempt to understand the author's intent ('). The desire to communicate some particular idea may require breaking some of the standard rules. Such exceptions must, however, be linguistically justified. In this he follows Kilwardby.
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Swarming wasps of the genus Epiponini generally place scent-markings on surfaces around the nest during the formation of swarm clusters. A. pallens, however, has a different mode of communication. Apoica has the Richards' Gland, an endocrine gland that is mechanistically important in signaling swarming. but apparently does not employ it during swarming.
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When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants.
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The wing of the cicada, the surface of which is covered in nanoscale pillars, induces lysis of bacteria. While the nano-pillars were not observed to prevent cell adhesion, they acted mechanistically to stretch microbial membranes to breakage. In vitro testing of the cicada wing demonstrated its efficacy against a variety of bacterial strains.
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The figure shows how, in the cholesterol biosynthesis pathway, squalene is converted to oxidosqualene, which is then converted to lanosterol by oxidosqualene cyclase. Lanosterol is a precursor to cholesterol. This final conversion occurs in many steps. Mechanistically, the enzyme catalyzes the formation of four rings along the long chain of the substrate (oxidosqualene), producing lanosterol.
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While the Barton reaction has not enjoyed the popularity or widespread use of many other organic reactions, together with the mechanistically similar Hofmann–Löffler reaction it represents one of the first examples of C-H activation chemistry, a field which is now the topic of much frontline research in industrial and academic chemistry circles.
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Erin M. Gibson is a glial and circadian biologist as well as an assistant professor in the Department of Psychiatry and Behavioral Sciences and the Stanford Center for Sleep Sciences and Medicine at Stanford University. Gibson investigates the role of glial cells in sculpting neural circuits and mechanistically probes how the circadian rhythm modulates glial biology.
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J Immunol. 2012 Sep 15;189(6):3007-17. except trace amount in thymus and immune cells, suggesting a selection pressure during evolution. Obviously, the immune selection pressure against iGb3 is mechanistically different from the well known anti-alpha-Gal antibodies, which caused the loss of alpha1,3-galactose epitope on glycoproteins in humans, apes, and old world monkeys.
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Mechanistically, KMT2C and KMT2D are required for the binding of H3K27 acetyltransferases CREB-binding protein (CBP) and/or p300 on enhancers, enhancer activation, and enhancer-promotor looping prior to gene transcription. The KMT2C and KMT2D proteins, rather than the KMT2C and KMT2D-mediated H3K4me1, control p300 recruitment to enhancers, enhancer activation, and transcription from promoters in embryonic stem cells.
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There is strong evidence that after activation of CaMKII, CaMKII plays a role in the trafficking of AMPA receptors into the membrane and then the PSD of the dendrite. Movement of AMPA receptors increases postsynaptic response to presynaptic depolarization through strengthening the synapses. This produces LTP. Mechanistically, CaMKII phosphorylates AMPA receptors at the P2 serine 831 site.
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Organozinc compounds derived from methylene bromide or iodide can electrophilically add to carbonyl groups to form terminal alkenes. The reaction is mechanistically related to the Tebbe reaction and can be catalyzed by various Lewis acids (e.g. TiCl4 or Al2Me6). The reaction is used to introduce deuterium into molecules for isotopic labeling or as an alternative to the Wittig reaction.
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Human memory is often thought to be a very complex process mechanistically, but very little is actually known about how memories are created and stored. When discussing human memory, there are three important categories to consider. This first type of memory is sensory, which involves rapid input of stimulus around a person. Sensory memory is constant, but fleeting.
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The orientation of dipole moments generated by helices within the active site generates an electropositive region for ideal reactivity with MIO. The partially positive regions in the active site may also help stabilize the charge of a carbanion intermediate. PAL is structurally similar to the mechanistically related histidine ammonia lyase, although PAL has approximately 215 additional residues.
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A mechanistically elegant study is especially important, as supporters argue that the quantity of work alone is in favor the ceRNA hypothesis. Two recent studies resolved this issue, demonstrating physiological effects and site- specific effects for ceRNA regulation. Supporters of the ceRNA hypothesis criticized the studies by Denzler et al. for their focus on competition for a single miRNA.
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The fusogens of classes I–III have many structural differences. However, the method they utilize to induce membrane fusion is mechanistically similar. When activated, all of these fusogens form elongated trimeric structures and bury their fusion peptides into the membrane of the target cell. They are secured in the viral membrane by hydrophobic trans-membrane regions.
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"Castillo, Jorge. "The Development of a Style" XXIII Bienal Internacional de Sao Paolo. 8 December 1996 He rejects the idea to paint mechanistically determined matters, instead emphasizing energy and life. It is what is considered a naïve style: one that "allowed him to caricature the social conventions of the bourgeoisie in his native Uruguay with a sort of wide-eyed innocence.
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Mechanistically, replicative senescence can be triggered by a DNA damage response due to the shortening of telomeres. Cells can also be induced to senesce by DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes, and cell-cell fusion. Normally, cell senescence is reached through a combination of a variety of factors (i.e., both telomere shortening and oxidative stress).
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MOPs are biomimetic materials that have potential for biomedical and biochemical applications. In order for the cage to work effectively and have biomedical relevance, it has to be chemically stable, biocompatible, and needs to operate mechanistically in aqueous media. Macromolecular cages in general can be used for a variety of applications (e.g. nanoencapsulation, biosensing, drug delivery, regulation of nanoparticle synthesis, and catalysis).
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The Hoffmann's reflex is sometimes described as the upper limb equivalent of the Babinski sign because both indicate upper motor neuron dysfunction. Mechanistically, they differ significantly; the finger flexor reflex is a simple monosynaptic spinal reflex involving the flexor digitorum profundus that is normally fully inhibited by upper motor neurons. The pathway producing the plantar response is more complicated, and is not monosynaptic.
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As BLVRB is a promiscuous enzyme catalysing the pyridine-nucleotide-dependent reduction of a variety of flavins, biliverdins, PQQ (pyrroloquinoline quinone), and ferric ion. Mechanistically it is a good model for BVR-A (biliverdin-IXalpha reductase), a potential pharmacological target for neonatal jaundice, and also a potential target for adjunct therapy to maintain protective levels of biliverdin-IXalpha during organ transplantation.
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This discovery helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. Bortezomib (Boronated MG132), a molecule developed by Millennium Pharmaceuticals and marketed as Velcade, is the first proteasome inhibitor to reach clinical use as a chemotherapy agent.United States Food and Drug Administration press release 13 May 2003. Access date 29 December 2006.
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Balsekar taught from the tradition of Advaita Vedanta nondualism. His teaching begins with the idea of an ultimate Source, Brahman, from which creation arises. Once creation has arisen, the world and life operate mechanistically according to both Divine and natural laws. While people believe that they are actually doing things and making choices, free will is in fact an illusion.
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Its expression in adipose tissues is increased following cold exposure. Genetic elevation of circulating PM20D1 in mice leads to accumulation of multiple circulating N-acyl amino acid species and a hypermetabolic phenotype. Conversely, PM20D1-KO exhibit bidirectional dysregulation of circulating N-acyl amino acids, insulin resistance, and glucose intolerance. Mechanistically, N-fatty acyl amino acids function as UCP1-independent uncouplers of mitochondrial respiration.
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Mechanistically this is because there are insufficient water molecules to effectively solvate the ions. This can result in ion-dipole interactions between the salts and hydrogen bonding species which are more favorable than normal hydrogen bonds. Common chaotropic agents used include n-butanol, ethanol, guanidinium chloride, lithium perchlorate, lithium acetate, magnesium chloride, phenol, 2-propanol, sodium dodecyl sulfate, thiourea, and urea.
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Lactacystin modifies the amino-terminal threonine of specific proteasome subunits. This work helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. The work led to the use of bortezomib to treat multiple myeloma. In 1996, Schreiber and co-workers used the small molecules trapoxin and depudecin to investigate the histone deacetylases (HDACs).
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Though the challenging identification of new genetic variants may not be the most efficient approach to developing mechanistically-informed drugs, it may lead to the development of more safe, individualized, and effective interventional strategies, risk- assessments and prognoses. Zuk et al. argue that biomedical research should focus on interacting molecular mechanisms of genetic variants already discovered. They argue that genetic interactions are common.
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Oxytocin has a positive impact on the awareness of social cues in individuals with social impairment. The release of oxytocin both mediates directly prosocial behavior and increases perception of social salience. The salience of mortality is also an active moderator of social salience. Mechanistically, increasing salience of mortality increases fear of isolation and thereby improves the rate of altruistic pro-social behavior.
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Human inputs of phosphate further encourage these red tides, so strong interest exists in learning more about dinoflagellates, from both medical and economic perspectives. Dinoflagellates are known to be particularly capable of scavenging dissolved organic phosphorus for P-nutrient, several HAS species have been found to be highly versatile and mechanistically diversified in utilizing different types of DOPs. The ecology of harmful algal blooms is extensively studied.
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Mechanistically, acetylating Lys304 sterically hinders the NADP+ from entering the NADP+ structural site, which reduces the stability of the enzyme. Cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates pentose phosphate pathway to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. Regulation can also occur through genetic pathways.
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His thesis investigating the evolution and development of mammalian molar cusp patterns was supervised by Irma Thesleff and Mikael Fortelius. This led to the description of enamel knot as molecular signaling centers in teeth. He also discovered and coined the term ‘secondary enamel knot’, previously overlooked signaling centers regulating tooth cusp development. This discovery helped to mechanistically link molecular regulation of growth and differentiation to shape.
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This acceleration of flowering by prolonged cold is a classic epigenetic process called vernalisation. FLC regulation involves an antisense-mediated chromatin mechanism that coordinately influences transcription initiation and elongation. As plants overwinter FLC expression is then epigenetically silenced through a cold-induced, cis-based, Polycomb switching mechanism. The group are mechanistically dissecting these conserved chromatin mechanisms and investigating how they have been modulated during adaptation.
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One of the products of the irradiation of CpW(CO)3Me in the presence of PPh3 is . The mechanism of said reaction was studied and theorized to be isolobal to the disproportionation of metal-metal bonded dimers involving 19-valence electron intermediates. The reactions are composed of isolobal fragments and the key intermediates of both reactions are isolobal. Thus, the reaction pathways are mechanistically isolobal.
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In recent years, studies with stem cells uncovered that neurogenesis still occurs in the adult hippocampus, where cognitive actions such as memory and learning are determined. This discovery provides an approach to understand mechanistically the CNS risk of space radiation. Accumulating data indicate that radiation not only affects differentiated neural cells, but also the proliferation and differentiation of neuronal precursor cells and even adult stem cells.
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Folic acid is first reduced to dihydrofolate and then to tetrahydrofolate. Each step consumes one molecule of NADPH (biosynthetically derived from vitamin B3) and produces one molecule of NADP. Mechanistically, hydride is transferred from NADPH to the C6 position of the pteridine ring. A one-carbon (1C) methyl group is added to tetrahydrofolate through the action of serine hydroxymethyltransferase (SHMT) to yield 5,10-methylenetetrahydrofolate (5,10-CH2-THF).
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Iodotyrosine deiodinase is thus necessary to keep levels of both iodide and thyroid hormones in balance. Dehalogenation in aerobic organisms is usually done through oxidation and hydrolysis; however, iodotyrosine deiodinase uses reductive dehalogenation. Iodotyrosine deiodinase and iodothyronine deiodinase have been determined as the only two known enzymes to catalyze reductive dehalogenation in mammals. Although these two enzymes perform similar functions, they are structurally and mechanistically different.
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It is assumed that any species of mosquito that causes an ordinary mosquito bite reaction in humans is capable of causing MBA. In addition to mosquitoes, the Diptera order includes numerous other types of biting insects such as midges (e.g. sand flies) and gnats. Bites by the latter insects or possibly some other insects may cause reactions that are mechanistically and clinically similar to those seen with mosquito bites.
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Rational enzyme engineering is characterized by making specific amino acid mutations based on mechanistic or structural information. While P450 enzymes are mechanistically well understood, mutations based on structural information are often limited by crystallization difficulty. Although, when obtainable, the high degree of flexibility and active site plasticity present in P450s make crystal structures largely obsolete for rational design. Another issue presents itself when attempting to expand substrate scope.
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It can occur during shallow dives, but does not usually become noticeable at depths less than . Except for helium and probably neon, all gases that can be breathed have a narcotic effect, although widely varying in degree. The effect is consistently greater for gases with a higher lipid solubility, and there is good evidence that the two properties are mechanistically related. As depth increases, the mental impairment may become hazardous.
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Most intriguingly, a recent study identified that TNF-induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/Nfkb2 in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.
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Descartes denied that animals had reason or intelligence.Waddicor, M. H., Montesquieu and the Philosophy of Natural Law (Leiden: Martinus Nijhoff Publishers, 1970), p. 63. He argued that animals did not lack sensations or perceptions, but these could be explained mechanistically. Whereas humans had a soul, or mind, and were able to feel pain and anxiety, animals by virtue of not having a soul could not feel pain or anxiety.
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Rejecting the cosmological and other proofs of God's existence, he denies that God can be regarded as the cause of movement. Movement can only be explained mechanistically from the nature of extension. The attribute of extension together with that of thought constitutes the world or universe, and its exists co-eternally with God. Wyermars reinterprets the dogma of creation ex nihilo as the absolute dependence of the world on God's power.
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Hypokalemic sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate. Individuals with this condition are sometimes diagnosed as having attention deficit hyperactivity disorder (ADHD), raising the possibility that a subtype of ADHD has a cause that can be understood mechanistically and treated in a novel way. It is not to be confused with hot tooth syndrome.
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Current noninvasive treatments used to combat fungal infections consist of a class of drugs known as azoles. Azole drugs such as voriconazole, itraconazole, and imidazole kill fungi by inhibiting the production of ergosterol—a critical element of fungal cell membranes. Mechanistically, these drugs act by inhibiting the fungal cytochrome p450 enzyme known as 14α-demethylase. However, A. fumigatus resistance to azoles is increasing, potentially due to the use of low levels of azoles in agriculture.
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Halohydrin dehalogenases mechanistically cleaves the carbon-halogen bond through the formation of an epoxide from a vicinal hydroxyl group. The substrate binds to the active site through hydrogen bonding that is coordinated by Ser132 and the deprotonated form of Tyr145. Failure to deprotonate Tyr145 by the Arg149 residue results in destabilization of the interaction between the enzyme and substrate resulting in reduced biological activity. The oxygen in Tyr145 deprotonates the hydroxyl group of the substrate.
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By blocking the M2 channel, the virus is unable to replicate because of impaired replication, protein synthesis, and exocytosis. Amantadine and rimantadine function in a mechanistically identical fashion, entering the barrel of the tetrameric M2 channel and blocking pore function—i.e., proton translocation. Resistance to the drug class is a consequence of mutations to the pore-lining residues of the channel, preventing both amantadine and rimantadine from inhibiting the channel in their usual way.
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Mechanistically, promoter escape occurs through DNA scrunching, providing the energy needed to break interactions between RNA polymerase holoenzyme and the promoter. In bacteria, it was historically thought that the sigma factor is definitely released after promoter clearance occurs. This theory had been known as the obligate release model. However, later data showed that upon and following promoter clearance, the sigma factor is released according to a stochastic model known as the stochastic release model.
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In chemistry, redistribution usually refers to the exchange of anionic ligands bonded to metal and metalloid centers. The conversion does not involve redox, in contrast to disproportionation reactions. Some useful redistribution reactions are conducted at higher temperatures; upon cooling the mixture, the product mixture is kinetically frozen and the individual products can be separated. In cases where redistribution is rapid at mild temperatures, the reaction is less useful synthetically but still important mechanistically.
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Exactly which RNAP they are most similar to is a topic of debate. Most other viruses that synthesize RNA use unrelated mechanics. Many viruses use a single-subunit DNA- dependent RNAP (ssRNAP) that is structurally and mechanistically related to the single-subunit RNAP of eukaryotic chloroplasts (RpoT) and mitochondria (POLRMT) and, more distantly, to DNA polymerases and reverse transcriptases. Perhaps the most widely studied such single-subunit RNAP is bacteriophage T7 RNA polymerase.
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Propargylglycine and β-cyanoalanine are two irreversible inhibitors of cystathionase used to treat elevated H2S levels. Mechanistically, the amino group of propargylglycine attacks the aldimine to form an external aldimine. The β position of the alkyne is then deprotonated to form the allene, which is then attacked by the phenol of Tyr114. The internal aldimine can regenerate, but the newly created vinyl ether sterically hinders the active site, blocking cysteine from attacking pyridoxal phosphate.
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Stratton's later work reflected these elements of his experience. He was also a scholar of the classics and translated some Greek philosophers. Stratton saw humans not as machines to be analyzed mechanistically, but also as seating will, emotion and drives, all of which had to analyzed as scientifically as the traditional psychological concepts of sensation, perception and memory. He also believed in a supreme actuality behind the world registered by our senses.
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Fluorophosphonate-rhodamine (FP-Rhodamine) activity-based probe for profiling of the serine hydrolase superfamily. In this probe the fluorophosphonate is the reactive group (RG) as it binds irreversibly to the active-site serine nucleophile of serine hydrolases and the tag is rhodamine, a fluorophore for in-gel visualization. Activity-based proteomics, or activity-based protein profiling (ABPP) is a functional proteomic technology that uses chemical probes that react with mechanistically related classes of enzymes.
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This theory is supported by multiple studies, which show that caloric restriction typically results in impaired fertility, but leave an otherwise healthy organism. Evolutionarily, an organism would want to delay reproduction to when resources were more plentiful. During a resource-barren period, it would evolutionarily unwise to invest resources in progeny that would be unlikely to survive in famine. Mechanistically, the NAD-dependent deacetylase Sirtuin 1 (SIRT-1) is upregulated during low-nutrient periods.
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Mitogen-activated protein kinase 4 is an enzyme that in humans is encoded by the MAPK4 gene. Mitogen-activated protein kinase 4 is a member of the mitogen- activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus where it phosphorylates nuclear targets. The Arabidopsis MAPK4 is important in signalling Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308.
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Ciona intestinalis is a hermaphrodite that releases sperm and eggs into the surrounding seawater almost simultaneously. It is self-sterile, and thus has been used for studies on the mechanism of self-incompatibility. Self/non-self-recognition molecules play a key role in the process of interaction between sperm and the vitelline coat of the egg. It appears that self/non-self recognition in ascidians such as C. intestinalis is mechanistically similar to self-incompatibility systems in flowering plants.
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Examination of dimerized and trimerized natural products has shown that an element of bilateral symmetry is often present. Bilateral symmetry refers to a molecule or system that contains a C2, Cs, or C2v point group identity. C2 symmetry tends to be much more abundant than other types of bilateral symmetry. This finding sheds light on how these compounds might be mechanistically created, as well as providing insight into the thermodynamic properties that make these compounds more favorable.
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A diagram explaining factors affecting arterial pressure Pathophysiology is a branch of medicine which explains the function of the body as it relates to diseases and conditions. The pathophysiology of hypertension is an area which attempts to explain mechanistically the causes of hypertension, which is a chronic disease characterized by elevation of blood pressure. Hypertension can be classified by cause as either essential (also known as primary or idiopathic) or secondary. About 90–95% of hypertension is essential hypertension.
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RNA silencing-based resistance is a powerful tool for engineering resistant crops. The advantage of RNAi as a novel gene therapy against fungal, viral and bacterial infection in plants lies in the fact that it regulates gene expression via messenger RNA degradation, translation repression and chromatin remodelling through small non-coding RNAs. Mechanistically, the silencing processes are guided by processing products of the double-stranded RNA (dsRNA) trigger, which are known as small interfering RNAs and microRNAs.
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In preclinical and early clinical studies, local application of IL-2 in the tumor has been shown to be clinical more effective in anticancer therapy than systemic IL-2 therapy, over a broad range of doses, without serious side effects. Tumour blood vessels are more vulnerable than normal blood vessels to the actions of IL-2. When injected inside a tumor, i.e. local application, a process mechanistically similar to the vascular leakage syndrome, occurs in tumor tissue only.
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These reactions demonstrate that the acidity of the methyl hydrogens in a pentamethylcyclopentadienyl complex can be considerably increased by the presence of the metal centre. Mechanistically, the reaction proceeds with potassium hydroxide deprotonating a methyl group and the resulting carbanion undergoing nucleophilic substitution with methyl iodide to form a new carbon–carbon bond. The compounds pentaphenylrhodocenium tetrafluoroborate [(η5-C5Ph5)Rh(η5-C5H5)]BF4, and pentamethylpentaphenylrhodocenium tetrafluoroborate [(η5-C5Ph5)Rh(η5-C5Me5)]BF4 have also been reported.
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The acylurea functional group is also found in some pharmaceutical drugs such as the anticonvulsants phenacemide, pheneturide, chlorphenacemide, and acetylpheneturide (which are phenylureides), and the sedatives acecarbromal, bromisoval, and carbromal (which are bromoureides). Others include apronal (apronalide), capuride, and ectylurea. As the barbiturates are basically cyclic ureas, these drugs are structurally and mechanistically related to them. The phenylureides are also closely related to the hydantoins, such as phenytoin, and may be considered ring-opened analogues of them.
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The exact mechanism of action of aristolochic acid is not known, especially in regards to nephropathy. The carcinogenic effects of aristolochic acids are thought to be a result of mutation of the tumor suppressor gene TP53, which seems to be unique to aristolochic acid-associated carcinogenesis. Nephropathy caused by aristolochic acid consumption is not mechanistically understood, but DNA adducts characteristic of aristolochic acid-induced mutations are found in the kidneys of AAN patients, indicating these might play a role.
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Except for helium and possibly neon, all gases that can be breathed have a narcotic effect under pressure,although widely varying in degree. Narcosis produces a state similar to drunkenness (alcohol intoxication), or nitrous oxide inhalation. It can occur during shallow dives, but does not usually become noticeable at depths less than about . The effect is consistently greater for gases with a higher lipid solubility, and there is good evidence that the two properties are mechanistically related.
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The Tr mechanism of DNA translocation is conserved by all ATP-dependent chromatin remodelers; two RecA-like lobes are mechanistically responsible for translocating the DNA. After binding two helical turns away from a nucleosome, the complex causes the shifting of the aforementioned nucleosome upstream one-two base pairs. In this ATP-driven mechanism, energy from hydrolysis causes the lobes to 'crawl' along the DNA towards the nucleosome dyad until the nucleosomes are correctly assembled, accessed or edited.
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Virtually any metal-R bond capable of transmetalation has been demonstrated. Indium derived nucleophiles require no copper or base. Note that this scope is applicable for the first generation coupling as the second and third generations are mechanistically distinct and have only been demonstrated with thioesters capable of forming the six-membered metallocycle, boronic acids, and stannanes. 450x450px The first-generation approach to cross coupling is run under anaerobic conditions using stoichiometric copper and catalytic palladium.
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The active site is exposed to the solvent via a perpendicular channel that consists of Arg150, Tyr146, Asp20, Pro67, His98, and His19. Although mechanistically similar to triosephosphate isomerase (TIM), MGS contains widely dissimilar protein folding that prevents structural alignment with TIM which suggests convergent evolution of their chemical reactions. However, Asp71 in MGS may act similarly to the Glu165, the catalytic base in TIM. Additionally, His19 and His98 may perform the role of the electrophilic catalyst similar to His95 in TIM.
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Mechanistically, eukaryotic translation termination matches its prokaryotic counterpart. In this case, termination of the polypeptide chain is achieved through the hydrolytic action of a heterodimer consisting of release factors, eRF1 and eRF3. Translation termination is said to be leaky in some cases as noncoding-tRNAs may compete with release factors to bind stop codons. This is possible due to the matching of 2 out 3 bases within the stop codon by tRNAs that may occasionally outcompete release factor base pairing.
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Figure 10. Protein domains in homologous recombination-related proteins are conserved across the three main groups of life: archaea, bacteria and eukaryotes. While the pathways can mechanistically vary, the ability of organisms to perform homologous recombination is universally conserved across all domains of life. Based on the similarity of their amino acid sequences, homologs of a number of proteins can be found in multiple domains of life indicating that they evolved a long time ago, and have since diverged from common ancestral proteins.
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It has been proposed that a second SPE-like enzyme similarly acts to activate Spatzle, as loss of SPE does not completely reduce the activity of Toll signalling, however no second SPE has yet been identified. A number of serine proteases are yet to be characterized, including many with homology to SPE. The Toll pathway also interacts with renal filtration of microbiota-derived peptidoglycan, maintaining immune homeostasis. Mechanistically, nephrocytes endocytose Lys-type PGN from systemic circulation and route it to lysosomes for degradation.
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The β3 isotype increases tumor aggressiveness by two distinct mechanisms. Incorporation of this isotype makes microtubule networks hypostable, allowing them to resist the cytotoxic effects of microtubule stabilizing drugs like taxanes or epothilones. Mechanistically, it was found that overexpression of β3-tubulin increases the rate of microtubule detachment from microtubule organizing centers, an activity that is suppressed by drugs such as paclitaxel. Expression of β3-tubulin also makes cells more aggressive by altering their response to drug-induced suppression of microtubule dynamics.
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Classical genetics is often referred to as the oldest form of genetics, and began with Gregor Mendel's experiments that formulated and defined a fundamental biological concept known as Mendelian inheritance. Mendelian inheritance is the process in which genes and traits are passed from a set of parents to their offspring. These inherited traits are passed down mechanistically with one gene from one parent and the second gene from another parent in sexually reproducing organisms. This creates the pair of genes in diploid organisms.
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In eukaryotes, about 10–20% of the genes are rhythmically expressed (as gauged by rhythms of mRNA abundance). However, in cyanobacteria, a much larger percentage of genes are controlled by the circadian clock. For example, one study has shown that the activity of essentially all promoters is rhythmically regulated. The mechanism by which this global gene regulation is mechanistically linked to the circadian clock is not known, but it may be related to rhythmic changes in the topology of the entire cyanobacterial chromosome.
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XBP1 is part of the endoplasmic reticulum (ER) stress response, the unfolded protein response (UPR). Conditions that exceed capacity of the ER provoke ER stress and trigger the unfolded protein response (UPR). As a result, GRP78 is released from IRE1 to support protein folding. IRE1 oligomerises and activates its ribonuclease domain through auto (self) phosphorylation. Activated IRE1 catalyses the excision of a 26 nucleotide unconventional intron from ubiquitously expressed XBP1u mRNA, in a manner mechanistically similar to pre-tRNA splicing.
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The alpha-ketol rearrangement is an interconversion of a hydroxyl alpha to a carbonyl to the complementary carbonyl and hydroxyl groups, with migration of a substituent. It is mechanistically equivalent to the benzyllic acid rearrangement at the point after the nucleophile attacks the 1,2-dicarbonyl. This variation of the reaction has been known to occur in many substrates bearing the acyloin functional group. The picture below shows the ring expansion of a cyclopentane to a cyclohexane ring as an example reaction.
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Ciona intestinalis (class Ascidiacea) is a hermaphrodite that releases sperm and eggs into the surrounding seawater almost simultaneously. It is self-sterile, and thus has been used for studies on the mechanism of self-incompatibility. Self/non-self- recognition molecules play a key role in the process of interaction between sperm and the vitelline coat of the egg. It appears that self/non-self recognition in ascidians such as C. intestinalis is mechanistically similar to self-incompatibility systems in flowering plants.
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Scene perseveration refers to seeing a previously-viewed, short stereotyped scene that continuously replays for several minutes. For example, a patient might view a person throwing a ball, and then an hour later, perceives the same action sequence repeated many times. The palinoptic scene usually has the same color and clarity as the original. Our understanding of visual memory considers a short scene as a unit of memory, similar to an image, thus scene perseveration is probably mechanistically related to formed image perseveration.
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C. intestinalis is an hermaphrodite that releases sperm and eggs into the surrounding seawater almost simultaneously. C. intestinalis is self-sterile, and thus has been used for studies on the mechanism of self-incompatibility. Self/non-self-recognition molecules are considered to play a key role in the process of interaction between sperm and the vitelline coat of the egg. It appears that self/non-self recognition in ascidians such as C. intestinalis is mechanistically similar to self- incompatibility systems in flowering plants.
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BHLHE41 is thought to be a critical regulator of the metastasis of triple- negative-breast cancer (TNBC). Regulated by the p63 metastasis suppressor, BHLHE41 inhibits TNBC through the inhibition of HIF-1α and hypoxia-inducible factor 2α (HIF-2α). Studies have shown that BHLHE41 is both required and sufficient to limit the expression of HIF-target genes, by mechanistically binding to HIFs and promoting proteasomal degradation. Breast cancer tumors that show high expression of BHLHE41 and CyclinG2 are believed to have a lower metastatic risk.
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Video of Mimosa pudica closing when touched in Hainan, China The leaflets also close when stimulated in other ways, such as touching, warming, blowing, shaking, which are all encapsulated within mechanical or electrical stimulation. These types of movements have been termed seismonastic movements. This reflex may have evolved as a defense mechanism to disincentivize predators, or alternatively to shade the plant in order to reduce water lossage due to evaporation. The main structure mechanistically responsible for the drooping of the leaves is the pulvinus.
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Mechanistically speaking, this has no effect on the overall reaction. In yeast, the forward direction is Mg^2+-dependent, while the reverse direction is Ca^2+-dependent. PAP1, a cytosolic phosphatidate phosphatase found in the lung, is also Mg^2+-dependent, but PAP2, a six-transmembrane-domain integral protein found in the plasma membrane, is not. Reactants and products of the reaction catalyzed by the enzyme phosphatidate phosphatase, and thus also those of the reverse reaction, which is catalyzed by the enzyme diacylglycerol kinase.
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Other important factors are the likelihoods that nucleases and competent cells will encounter DNA molecules, the relative inefficiencies of nucleotide uptake from the environment and from the periplasm (where one strand is degraded by competent cells), and the advantage of producing ready-to-use nucleotide monophosphates from the other strand in the cytoplasm. Another complicating factor is the self-bias of the DNA uptake systems of species in the family Pasteurellaceae and the genus Neisseria, which could reflect either selection for recombination or for mechanistically efficient uptake.
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In 1983, Cacchi and coworkers disclosed a reductive Heck arylation of enones and enals in the presence of a trialkylamine base, tetrabutylammonium halide, and formic acid additive. Under these conditions, the conjugate addition product is formed preferentially to the vinylic substitution (Mizoroki–Heck) product in high yield and selectivity. Notably, reductive Heck coupling on enones/enals features some mechanistically distinct aspects, as described in studies by Cacchi and later Minnaard. Both the conjugate addition and vinylic substitution mechanisms proceed through a common alkylpalladium(II) intermediate 34.
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Intrinsic Immunity combines aspects of the two traditional branches of the immune system - adaptive and innate immunity – but is mechanistically distinct. Innate cellular immunity recognizes viral infection using toll-like receptors (TLRs), or pattern recognition receptors, which sense Pathogen- associated molecular patterns (PAMPs), triggering the expression of nonspecific antiviral proteins. Intrinsic immune proteins, however, are specific both in virus recognition and their mechanism of viral attenuation. Like innate immunity, however, the intrinsic immune system does not respond differently upon repeat infection by the same pathogen.
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In Drosophila melanogaster, SCRIB is involved in synaptic function, neuroblast differentiation, and epithelial polarization. Mechanistically, the human homolog is a scaffold protein linked to cellular differentiation centered on the regulation of epithelial as well as neuronal morphogenesis. Deficiency in SCRIB impairs many aspects of cell polarity and cell movement. SCRIB is also likely involved in establishing apical-basal polarity as well as progression from the G1 phase to S phase in the cell cycle as a result of its relationship with cell proliferation and exocytosis.
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RNR inhibitors, gemcitabine) or treatments (e.g. ionizing radiation) and so more combination therapies are currently been studied to reduce biological resistance mechanisms and drug tolerance in patients. For example, gemcitabine is a FDA-approved pyrimidine nucleoside analogue and a dCK activity based prodrug that has been used to treat pancreatic, breast, bladder and non-small cell lung cancer. Mechanistically, dCK, which uptakes preformed nucleosides, adds the first phosphoryl group on dFdC (gemcitabine's original form as a deoxycytidine analog) to convert it into dFdCMP, its monophosphate form.
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Later, five more human IAPs were discovered which included XIAP, cIAP1 , C-IAP2, NAIP, Livin and Survivin. The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase-7, thereby inhibiting their activation and preventing apoptosis. Also cIAP1 and cIAP2 have been shown to bind caspases, although how the IAPs inhibit apoptosis mechanistically at the molecular level is not completely understood. Activity of XIAP is blocked by binding to DIABLO (Smac) and HTRA2 (Omi) proteins released from mitochondria after proapoptotic stimuli.
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Survivin, like the others, was discovered by its structural homology to IAP family of proteins in human B-cell lymphoma. The human IAPs, XIAP, c-IAPl, C-IAP2 have been shown to bind to caspase-3 and -7, which are the effector caspases in the signaling pathway of apoptosis. It is not known with absolute certainty though, how the IAPs inhibit apoptosis mechanistically at the molecular level. A common feature that is present in all IAPs in the presence of a BIR (Baculovirus IAP Repeat, a ~70 amino acid motif) in one to three copies.
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Although mechanistically simple and quite robust on molecular level, several issues need to be addressed before an in vivo implementation of computational genes can be considered. First, the DNA material must be internalised into the cell, specifically into the nucleus. In fact, the transfer of DNA or RNA through biological membranes is a key step in the drug delivery. Some results show that nuclear localisation signals can be irreversibly linked to one end of the oligonucleotides, forming an oligonucleotide-peptide conjugate that allows effective internalisation of DNA into the nucleus.
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While dispersal is a key aspect to all three population survival strategies, evolutionary rescue is the only one driven by adaptive evolution mechanistically. Demographic rescue is simply a dynamic driven by source-sink immigration dynamics, whereas genetic rescue is primarily driven by hybridization in combination with immigration. Given the reliance on immigration, it can be difficult to disentangle demographic rescue from genetic rescue. The distinction between these three rescue strategies may be difficult to prove, if it exists, although rescue from negative population growth may be a hallmark.
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Hypokalemic sensory overstimulation is a term coined by MM Segal and colleagues to describe a syndrome of sensory overstimulation, ineffectiveness of the local anesthetic lidocaine, and in females, premenstrual syndrome. This initial report was followed by discussion in a second article of tens of families with apparent autosomal dominant inheritance of this condition. The similarities were described clinically to ADHD and mechanistically and therapeutically to disorders of ion channels, in particular to the muscle disorder hypokalemic periodic paralysis. Some females with premenstrual syndrome may have the same autosomal dominant disorder underlying their symptoms.
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These sensors also formulate input for cell-specific homeostatic plasticity regulation systems. In synaptic scaling, neurons use this information to determine a scale factor. Each neuron subsequently uses the scaling factor to globally scale (either up-regulate or down-regulate) the quantity of transmembrane AMPA receptors at all post-synaptic sites. Some research indicates there are two mechanistically distinct forms of homeostatic plasticity involving trafficking or translation of AMPA receptors at post- synapse of synaptic connections: # Local synthesis of AMPA receptors: Local area AMPA receptor synthesis takes place within a time scale of 4 hours.
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Endomorphins maintain a variety of functions. Mechanistically, they bind inhibitory μ-opioid G-protein receptors, which act to close calcium ion channels and open potassium ion channels in the membranes of bound neurons. The elimination of calcium influx and facilitation of potassium ion efflux prevents neuronal depolarization, inhibits the generation of action potentials, and depresses the activity of excitatory neurons. In other instances, endomorphin binding causes excitation, where its activation of phospholipase C and adenylyl cyclase initiates an increase in calcium ion concentration, cellular depolarization, and the release of norepinephrine and serotonin.
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Eribulin is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin B, the parent molecule being a potent naturally occurring mitotic inhibitor with a unique mechanism of action found in the sponge genus Halichondria. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules. Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein apoptosis of cancer cells is induced following prolonged and irreversible mitotic blockade.
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In contrast to the canonical signaling that relies on NEMO-IKK2 mediated degradation of IκBα, -β, -ε, non-canonical signaling depends on NIK mediated processing of p100 into p52. Given their distinct regulations, these two pathways were thought to be independent of each other. However, it was found that syntheses of the constituents of the non-canonical pathway, viz RelB and p52, are controlled by canonical IKK2-IκB-RelA:p50 signaling. Moreover, generation of the canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are mechanistically interlinked.
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The EFI is developing an integrated sequence-structure based strategy for functional assignment by predicting the substrate specificities of unknown members of mechanistically diverse enzyme superfamilies. The approach leverages conserved features within a given superfamily such as known chemistry, identity of active site functional groups, and composition of specificity-determining residues, motifs, or structures to predict function but relies on multidisciplinary expertise to streamline, refine, and test the predictions. The integrated sequence-strategy under development will be generally applicable to deciphering the ligand specificities of any functionally unknown protein.
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Darwin's pangenesis theory attempted to explain the process of sexual reproduction, inheritance of traits, and complex developmental phenomena such as cellular regeneration in a unified mechanistic structure. Yongshen Liu wrote that in modern terms, pangenesis deals with issues of "dominance inheritance, graft hybridization, reversion, xenia, telegony, the inheritance of acquired characters, regeneration and many groups of facts pertaining to variation, inheritance and development." Mechanistically, Darwin proposed pangenesis to occur through the transfer of organic particles which he named 'gemmules.' Gemmules, which he also sometimes referred to as },Allaby, Michael.
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Restrictive dermopathy (RD) is caused either by the loss of the gene ZMPSTE24, which encodes a protein responsible for the cleavage of farnesylated prelamin A into mature non-farnesylated lamin, or by a mutation in the LMNA gene. This results in the accumulation of farnesyl-prelamin A at the nuclear membrane. Mechanistically, restrictive dermopathy is somewhat similar to Hutchinson–Gilford progeria syndrome (HGPS), a disease where the last step in lamin processing is hindered by a mutation that causes the loss of the ZMPSTE24 cleavage site in the lamin A gene.
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The ligand-binding mechanisms of P2Y receptors are not currently well established. The binding complex of P2Y receptors with ATP is of significant interest, as no P2Y receptor contains amino acids sequences similar to any of the many established ATP-binding sites. Recent x-ray crystallography of the human P2Y12 receptor has shown several structural irregularities in regions that are typically highly conserved across GPCRs. In contrast to the unusual structure and behavior of the extracellular ligand binding domains, P2Y intracellular domains appear to be structurally and mechanistically similar to other GPCRs.
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Human phenotypes are predicted from DNA using direct or indirect methods. With direct methods, genetic variants mechanistically linked with variable expression of the relevant phenotypes are measured and used with appropriate statistical methodologies to infer trait value. With indirect methods, variants associated with genetic component(s) of ancestry that correlate with the phenotype of interest, such as Ancestry Informative Markers, are measured and used with appropriate statistical methodologies to infer trait value. The direct method is always preferable, for obvious reasons, but depending on the genetic architecture of the phenotype, is not always possible.
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Mechanistically, the causes of pelvic floor dysfunction are two-fold: widening of the pelvic floor hiatus and descent of pelvic floor below the pubococcygeal line, with specific organ prolapse graded relative to the hiatus. Associations include obesity, menopause, pregnancy and childbirth.Abbey Hospitals Gynaecology and Vaginal Repair information Some women may be more likely to developing pelvic floor dysfunction because of an inherited deficiency in their collagen type. Some women may have congenitally weak connective tissue and fascia and are therefore at risk of stress urinary incontinence and pelvic organ prolapse.
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Ligands do not bind to NGFIB, so modulation occurs at the level of protein expression and posttranslational modification. Besides these, NR4A1 can mediate T cell function, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumor and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector gene expression by inhibiting AP-1 function.
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The regulation of stem cell self-renewal Morrison developed methods to distinguish self-renewing stem cells from multipotent progenitors in the blood-forming system and in the peripheral and central nervous systems. This work showed that self-renewal potential is determined cell-intrinsically in stem cells and made it possible to identify gene products that regulate stem cell maintenance across multiple tissues. The Morrison laboratory identified a series of key stem cell self- renewal regulators, revealing several important principles. First, stem cell self-renewal is mechanistically distinct from restricted progenitor proliferation.
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Much of the ongoing work in the field of carbonate-associated sulfate is dedicated to characterizing sources of variation in the CAS record, answering questions like: how are sulfate ions incorporated into the mineral structure of different Ca-carbonate and Ca-Mg-carbonate morphotypes, mechanistically speaking? And which morphotypes are most likely to contain CAS derived from primary marine sulfate? Just as for other geochemical proxies, the utility and reliability of CAS measurements will improve with the advent of more sensitive measurement techniques, and the characterization of more isotope standards.
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Each subunit has three different structural domains: a short N-terminal epidermal growth factor (EGF) domain; an α-helical membrane-binding moiety; and a C-terminal catalytic domain. PTGS (COX, which can be confused with "cytochrome oxidase") enzymes are monotopic membrane proteins; the membrane-binding domain consists of a series of amphipathic α helices with several hydrophobic amino acids exposed to a membrane monolayer. PTGS1 (COX-1) and PTGS2 (COX-2) are bifunctional enzymes that carry out two consecutive chemical reactions in spatially distinct but mechanistically coupled active sites.
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Examples of aldol reactions in biochemistry include the splitting of fructose-1,6-bisphosphate into dihydroxyacetone and glyceraldehyde-3-phosphate in the fourth stage of glycolysis, which is an example of a reverse ("retro") aldol reaction catalyzed by the enzyme aldolase A (also known as fructose-1,6-bisphosphate aldolase). In the glyoxylate cycle of plants and some prokaryotes, isocitrate lyase produces glyoxylate and succinate from isocitrate. Following deprotonation of the OH group, isocitrate lyase cleaves isocitrate into the four-carbon succinate and the two-carbon glyoxylate by an aldol cleavage reaction. This cleavage is very similar mechanistically to the aldolase A reaction of glycolysis.
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Using single channel electrophysiological recordings, it was found that RyR1 channels exposed to vejocalcin move from an open state to a subconductance open state, with the latter conducting approximately 60% of the full-conductance level. Evidence from [3H]ryanodine binding assays shows that vejocalcin is able to enhance [3H]ryanodine binding to RyR1. This effect of vejocalcin is dose-dependent and happens at all Ca2+ levels, with an apparent dissociation constant Kd= 3.7 ± 0.4 nM. Mechanistically, vejocalcin is thought to promote this action by increasing the “openness” of the channel in a long-lasting, reversible and transient manner.
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The vinylcyclopropane rearrangement or vinylcyclopropane-cyclopentene rearrangement is a ring expansion reaction, converting a vinyl-substituted cyclopropane ring into a cyclopentene ring. Vinylcyclopropane Rearrangement Intense experimental as well as computational investigations have revealed that mechanistically, the vinylcyclopropane rearrangement can be thought of as either a diradical-mediated two-step and/or orbital-symmetry-controlled pericyclic process. The amount by which each of the two mechanisms is operative is highly dependent on the substrate. Due to its ability to form cyclopentene rings the vinylcyclopropane rearrangement has served several times as a key reaction in complex natural product synthesis.
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Fis can modulate supercoiling by repressing the transcription of the genes encoding DNA gyrase. There is genetic evidence to suggest that HU controls supercoiling levels by stimulating DNA gyrase and reducing the activity of Topo I. In support of the genetic studies, HU was shown to stimulate DNA gyrase-catalyzed decatenation of DNA in vitro. It is unclear mechanistically how HU modulates the activities of the gyrase and Topo I. HU might physically interact with DNA gyrase and Topo I or DNA organization activities of HU such as DNA bending may facilitate or inhibit the action of DNA gyrase and Topo I respectively.
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DD-transpeptidase is mechanistically similar to the proteolytic reactions of the trypsin protein family. DD-transpeptidase catalytic mechanism Crosslinking of peptidyl moieties of adjacent glycan strands is a two-step reaction. The first step involves the cleavage of the D-alanyl-D-alanine bond of a peptide unit precursor acting as carbonyl donor, the release of the carboxyl-terminal D-alanine, and the formation of the acyl- enzyme. The second step involves the breakdown of the acyl-enzyme intermediate and the formation of a new peptide bond between the carbonyl of the D-alanyl moiety and theamino group of another peptide unit.
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The reduced catalyst then shuttles the transferred electron to the halogenated substrate, reducing the weak C-X bond and inducing fragmentation. Diagram of the catalytic cycle proposed for the mechanism of their tin-free reduction of activated halogens Unactivated carbon-iodine bonds can be reduced using the strongly reducing photocatalyst tris-(2,2’-phenylpyridine)iridium (Ir(ppy)3). This reaction is mechanistically distinct from the previous transformation of activated bromides and chlorides. The increased reduction potential of Ir(ppy)3 compared to [Ru(bipy)3]2+ allows direct reduction of the carbon-iodine bond without interacting with a stoichiometric reductant.
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In line with the hypothesis that syndapin I induces bulk endocytosis, characterization of syndapin I knock-out mice revealed a crucial role of syndapin I in presynaptic membrane trafficking processes and accumulation of endocytic intermediates was especially evident under high-capacity retrieval conditions. Mechanistically, the F-BAR domain protein syndapin I possibly acts through further interactions with Arp2/3 and N-WASP. The GTPase dynamin then pinches off the large membrane-vacuole, which is either degraded or reused for synaptic vesicle production (possibly through clathrin coating). Clathrin-mediated endocytosis and bulk endocytosis appear to occur concurrently in highly active synaptic terminals.
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The degradation of this enzyme results from phosphorylation and subsequent ubiquitination induced by cigarette smoke. In rat and mouse models, cigarette smoke was observed to increase acetylation of lysine 9 on histone H3 (H3K9), lysine 12 on histone H4 (H4K12) and phosphorylation of serine 10 on histone H3 (H3S10). These marks are associated with an increase in gene expression and prevent the accumulation of repressive histone modifications. Mechanistically, the increased frequency of these marks, especially the modifications on histone H3, are linked to the activation of IKK-α which directly phosphorylates histone H3 as a consequence of exposure to cigarette smoke.
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Recent studies suggested that the function the non-canonical NF-κB pathway is modulated by canonical NF-κB signalling. For example, syntheses of the constituents of the non-canonical pathway, viz RelB and p52, are controlled by canonical IKK2-IκB-RelA:p50 signalling. Moreover, generation of canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are mechanistically interlinked. These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway.
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Due to the wide variety of type IV secretion systems in both origin and function, it is difficult to state much mechanistically about the group as a whole. In general, after DNA is packaged in a conjugative system it is recruited by ATPase analogues to the VirD4 coupling protein, then translocated through the pilus. In A. tumefaciens specifically, the DNA passes through a characterized chain of enzymes before reaching the pilus. The DNA is recruited by VirD4, then VirB11, then to the intermembrane proteins (VirB6, and VirB8), moved to VirB9, and finally sent to the pilus (VirB2).
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Mechanistically, RHAMM has been shown to promote cell motility through a number of different pathways. As with CD44, RHAMM can promote focal adhesion turnover by controlling focal adhesion kinase (FAK) phosphorylation and cooperating with the α4β1 and α5β1 integrins. RHAMM also activates a number of downstream kinases including enhancing the intensity and sustaining the duration of ERK1 / ERK2 activation through the map kinase (MAPK) pathway, pp60 (c-src), and the downstream targets of rho kinase (ROK). Finally, once a metastatic lesion has been established, RHAMM can cooperate with CD44 to promote angiogenesis by promoting migration of neighboring endothelial cells towards the tumor.
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Compared to other carbohydrates, isomaltulose ingestion is associated with higher rates of fat oxidation and lower rates of fat storage. Mechanistically this involves a lower blood glucose concentration, which then provides a reduced stimulus to insulin secretion, which in turn allows more fatty acids to be released from adipose tissue for oxidation as an energy source. The lower insulin concentration also decreases carbohydrate oxidation, allowing more fatty acids to be oxidized. A lower insulin concentration also lowers the rate of liver free fatty acid recycling via plasma triglycerides and reduces the storage of triglycerides in adipose tissue.
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When this happens, calnexin will send the incorrectly folded protein to be degraded through other sugar recognizing proteins that were again discovered with Thomas and separately by Helenius and Parodi. This represents the first protein folding code to be mechanistically solved and represents the basis for several protein misfolding diseases. Using the new technology of proteomics that Dr. Bergeron pioneered in Quebec and Canada, he elucidated the major resident proteins of the secretory pathway common to all cells. This led to the discovery of several proteins characterized for the first time involved in organ biogenesis and disease.
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His commitment to public service was demonstrated by his long tenure as a member of the Science Board to the US Food and Drug Administration (FDA). FitzGerald's work contributed substantially to the development of low-dose aspirin to prevent heart attacks and strokes. FitzGerald's lab was the first to predict and then mechanistically explain the cardiovascular hazard from Nonsteroidal anti-inflammatory drugs (NSAIDs), a common class of painkiller. His work showing that selective COX-2 inhibitors depress the production of prostacyclin in the endothelium, thereby increasing cardiovascular risk, was instrumental in the withdrawal of Vioxx (rofecoxib) from the U.S. market in 2004.
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Yohimbine, historically used as an aphrodisiac, is sometimes used in veterinary medicine (although now largely replaced by atipamezole) for reversing the effects of α2s such as medetomidine that are used as sedatives during surgery. The tetracyclic antidepressants mianserin and mirtazapine are α2 blockers, although their efficacy as antidepressants may come from their activity at other receptor sites. Mechanistically, α2 blockers increase adrenergic, dopaminergic and serotonergic neurotransmitters and induce insulin secretion, decreasing blood sugar levels. Withdrawal from α2 blockers can be difficult or dangerous as the global downregulation of neurotransmitters may cause symptoms of depression and other neurological problems, and increased blood sugar levels together with decreased insulin sensitivity can cause diabetes.
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Some of the studies cited above have suggested that 9-HODEs, 13-HODEs, their hydroperoxy counterparts, and/or their oxo counterparts contribute mechanistically to these oxidative- stress-related diseases. That is, the free radical oxidation of linoleic acid makes these products which then proceed to contribute to the tissue injury, DNA damage, and/or systemic dysfunctions that characterize the diseases. Furthermore, certain of these HODE-related products may serve as signals to activate pathways that combat the reactive oxygen species and in this and other ways the oxidative stress. It remains unclear whether or not the HODEs and their counterparts promote, dampen, or merely reflect oxidative-stress- related diseases.
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Artwork of a Civil Protection Officer Some elements of the Combine's appearance, such as that of the Advisor, are inspired by the works of Frank Herbert. The towering Striders seen throughout Half-Life 2 and its subsequent episodes are based directly on the Martian tripods of the H.G. Wells novel The War of the Worlds, where said Martians invade Victorian England, using the tripods as their main "weapon". The name "Combine" itself is a tribute to Ken Kesey's novel One Flew Over the Cuckoo's Nest, which features a collection of authorities which mechanistically manipulate and process individuals. During Half-Life 2s development, various concepts for Combine non-player characters were cut.
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Philosophical atomism is a reductive argument, proposing not only that everything is composed of atoms and void, but that nothing they compose really exists: the only things that really exist are atoms ricocheting off each other mechanistically in an otherwise empty void. Atomism stands in contrast to a substance theory wherein a prime material continuum remains qualitatively invariant under division (for example, the ratio of the four classical elements would be the same in any portion of a homogeneous material). Indian Buddhists, such as Dharmakirti ( 6th or 7th century) and others, developed distinctive theories of atomism, for example, involving momentary (instantaneous) atoms (kalapas) that flash in and out of existence.
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EFS regulates T-cell function and maturation, preventing expansion of autoreactive clones and pathological immune responses. Two studies that have reported that EFS expression in medullar thymus epithelial cells is important for negative selection of T-cells during their development, which implies an important role of EFS in maintaining immune homeostasis and autoimmunity prevention. In these studies, mice with defective EFS progressed normally during embryogenesis but then developed massive inflammatory lesions in multiple tissues that bore a striking histological resemblance to inflammatory bowel diseases such as Crohn’s disease. Mechanistically, EFS expressed in medullary thymic epithelial cells (mTECs) is crucial for their functional maturation and growth factor- mediated expansion.
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The proneural genes also have an important role in the development of distinct types of sensory organs, namely chordotonal organs (proprioceptorsthat detect mechanical and sound vibrations) and external sensory organs. Members of achaete-scute complex, such as achaete and scute, as well as ‘’atonal’’ and ‘’daughterless’’ confer to ectodermal cells the ability to become sensory mother cells (SMCs). In the development of sensory organs there are two main phases: determination and differentiation that may not be mechanistically separable. Proneural proteins are involved in both processes, through the activation of the downstream “differentiating genes” that in turn regulate the induction of sensory-organ-subtype characteristics.
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These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non- canonical pathway. Most intriguingly, a recent study identified that TNF- induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/Nfkb2 in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.
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A man cutting open a Lithium-ion battery for use in an Electric Vehicle Lithium-ion (and the mechanistically similar lithium polymer) batteries, were initially developed and commercialized for use in laptops and consumer electronics. With their high energy density and long cycle life they have become the leading battery type for use in EVs. The first commercialized lithium-ion chemistry was a lithium cobalt oxide cathode and a graphite anode first demonstrated by N. Godshall in 1979, and by John Goodenough, and Akira Yoshino shortly thereafter. Godshall, Ned A. (18 May 1980) Electrochemical and Thermodynamic Investigation of Ternary Lithium-Transition Metal-Oxygen Cathode Materials for Lithium Batteries.
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Lastly, autoimmune disease patients with SLE, Sjögren syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. A role of the proteasome subunit alpha type-3 has been linked in underlying mechanisms of human malignancies. It has been suggested that Cables1 as a novel p21 regulator through maintaining p21 stability and supporting the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21. In this process, Cables 1 mechanistically interferes the proteasome subunit alpha type-3 (PMSA3) hereby binding to p21 to induce cell death and inhibit cell proliferation.
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Mammalian cells with mutant ERCC1–XPF are moderately more sensitive than normal cells to agents (such as ionizing radiation) that cause double- stranded breaks in DNA. Particular pathways of both homologous recombination repair and non-homologous end-joining rely on ERCC1-XPF function. The relevant activity of ERCC1–XPF for both types of double-strand break repair is the ability to remove non-homologous 3′ single-stranded tails from DNA ends before rejoining. This activity is needed during a single-strand annealing subpathway of homologous recombination. Trimming of 3’ single-stranded tail is also needed in a mechanistically distinct subpathway of non-homologous end-joining, dependent on the Ku proteins.
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Descartes, like Galen, thought of the nervous system in hydraulic terms. He believed that the highest cognitive functions are carried out by a non- physical res cogitans, but that the majority of behaviors of humans, and all behaviors of animals, could be explained mechanistically. The first real progress toward a modern understanding of nervous function, though, came from the investigations of Luigi Galvani (1737–1798), who discovered that a shock of static electricity applied to an exposed nerve of a dead frog could cause its leg to contract. Since that time, each major advance in understanding has followed more or less directly from the development of a new technique of investigation.
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The unusual alkyl nitrite starting material of the Barton reaction is prepared by attack of an alcohol on a nitrosylium cation generated in situ by dehydration of doubly protonated nitrous acid. This series of steps is mechanistically identical to the first half of the mechanism formation of the more well-known aryl and alkyl diazonium salts. While the synthesis of alkyl nitrites from nitrosyl chloride is known and oft-employed in the context of complex molecule synthesis, the reaction is reversible and the products are in thermodynamic equilibrium with the starting material. Furthermore, nitrosyl chloride is a powerful oxidizing agent, and oxidation of the alcohols with concomitant chlorination has been observed.
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1903 Volume 40, Part 2, 1539 It is detected infrequently, is best heard at the left sternal border, and sounds similar to aortic insufficiency, although it is without decrescendo. Its location, timing, association with severe anemia, and resolution upon correction of anemia, are consistent mechanistically with a functional murmur arising from high volume flow dynamics in the left main coronary artery, which has almost entirely diastolic flow. It is named for Richard Clarke Cabot and his colleague, Locke. They reported on a series of three patients who had been clinically diagnosed with heart valve disease, but who had normal valvular anatomy at subsequent autopsy.
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RNA silencing describes several mechanistically related pathways which are involved in controlling and regulating gene expression. RNA silencing pathways are associated with the regulatory activity of small non-coding RNAs (approximately 20–30 nucleotides in length) that function as factors involved in inactivating homologous sequences, promoting endonuclease activity, translational arrest, and/or chromatic or DNA modification. In the context in which the phenomenon was first studied, small RNA was found to play an important role in defending plants against viruses. For example, these studies demonstrated that enzymes detect double-stranded RNA (dsRNA) not normally found in cells and digest it into small pieces that are not able to cause disease.
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Dianin's method for preparing bisphenol A from 1891 remains the most widely-known approach to this important compound, though the method has been refined for industrial-scale synthesis. It involves the catalysed condensation of a 2:1 mixture of phenol and acetone in the presence of concentrated hydrochloric acid or sulfuric acid. The reaction proceeds readily at room temperature producing a crude product containing a great variety of side products (including Dianin's compound) in a matter of hours. The overall equation is simple, with water as the only by-product: 700px Mechanistically, the acid catalyst converts the acetone to a carbenium ion that undergoes an electrophilic aromatic substitution reaction with the phenol, producing predominantly para-substituted products.
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The Fbxl3 gene function was independently identified in 2007 by three groups lead by Michele Pagano, Joseph S. Takahashi, Dr. Patrick Nolan and Michael Hastings, respectively. Takahashi used forward genetics N-ethyl-N-nitrosourea (ENU) mutagenesis to screen for mice with varied circadian activity which led to the discovery of the Overtime (Ovtm) mutant of the Fbxl3 gene. Nolan discovered the Fbxl3 mutation After hours (Afh) by a forward screen assessing wheel activity behavior of mutagenized mice. The phenotypes identified in mice were mechanistically explained by Pagano who discovered that the FBXL3 protein is necessary for the reactivation of the CLOCK and BMAL1 protein heterodimer by inducing the degradation of CRY proteins.
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Homologation reactions like the Kowalski ester homologation provide simple examples of insertion process in organic synthesis. In the Arndt-Eistert reaction, a methylene unit is inserted into the carboxyl-carbon bond of carboxylic acid to form the next acid in the homologous series. Organic Syntheses provides the example of t-BOC protected (S)-phenylalanine (2-amino-3-phenylpropanoic acid) being reacted sequentially with triethylamine, ethyl chloroformate, and diazomethane to produce the α-diazoketone, which is then reacted with silver trifluoroacetate / triethylamine in aqueous solution to generate the t-BOC protected form of (S)-3-amino-4-phenylbutanoic acid. :Homologation of N-boc-phenylalanine Mechanistically, the α-diazoketone undergoes a Wolff rearrangement to form a ketene in a 1,2-rearrangement.
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Interference involves the crRNAs within a multi-protein complex called CASCADE, which can recognize and specifically base-pair with regions of inserting complementary foreign DNA. The crRNA-foreign nucleic acid complex is then cleaved, however if there are mismatches between the spacer and the target DNA, or if there are mutations in the PAM, then cleavage will not be initiated. In the latter scenario, the foreign DNA is not targeted for attack by the cell, thus the replication of the virus proceeds and the host is not immune to viral infection. The interference stage can be mechanistically and temporally distinct from CRISPR acquisition and expression, yet for complete function as a defense system, all three phases must be functional.
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Organotantalum compounds are invoked as intermediates in C-alkylation of secondary amines with 1-alkenes using Ta(NMe2)5. The chemistry developed by Maspero was later brought to fruition when Hartwig and Herzon reported the hydroaminoalkylation of olefins to form alkylamines: Hartwig hydroaminoalkylation reaction scheme Mechanistically, the first step of the catalytic cycle is believed to be the C-H activation (via β-hydrogen abstraction) of the bisamide, which results in the formation of a metallaaziridine. Subsequent olefin insertion, protonolysis of the tantalum- carbon bond, and β-hydrogen abstraction affords the alkylamine product. Notable advancements in this area were also made by Doye and Schafer when they showed tantalum catalyzed hydroaminoalkylations were exclusively branch selective and highly diastereoselective.
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Sources of resistance exist in Prunus, but are not common. A team of scientists from the United States and France has genetically engineered a plum pox-resistant plum called C5,GM Crop Database ARS-PLMC5-6 (C5) Center for Environmental Risk Assessment, 24 February 2009, Retrieved 25 April 2011 and the resistance can be transferred through hybridization to other plum trees. The transgenic plum expresses a plum pox virus coat protein, the plant produces the coat protein mRNA and it is processed by a system called post transcriptional gene silencing (PTGS), which functions like the plants' immune system and is mechanistically similar to RNAi. C5 provides a unique source of germplasm for future breeding programs worldwide.
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Multiple studies have found support that increasing potassium concentrations may increase stomatal opening in the mornings, before the photosynthesis process starts, but that later in the day sucrose plays a larger role in regulating stomatal opening. Stomatal density and aperture (length of stomata) varies under a number of environmental factors such as atmospheric CO2 concentration, light intensity, air temperature and photoperiod (daytime duration). Decreasing stomatal density is one way plants have responded to the increase in concentration of atmospheric CO2 ([CO2]atm). Although changes in [CO2]atm response is the least understood mechanistically, this stomatal response has begun to plateau where it is soon expected to impact transpiration and photosynthesis processes in plants.
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A chromate ester is a chemical structure that contains a chromium atom (symbol Cr) in a +6 oxidation state that is connected via an oxygen (O) linkage to a carbon (C) atom. The Cr itself is in its chromate form, with several oxygens attached, and the Cr–O–C attachment makes this chemical group structurally similar to other ester functional groups. They can be synthesized from various chromium(VI) metal compounds, such as CrO3, chromium chloride complexes, and aqueous chromate ions, and tend to react via redox reactions to liberate chromium(IV). Chromate esters are the key reactive intermediates in the Jones oxidation, the mechanistically related oxidations using pyridinium dichromate or pyridinium chlorochromate.
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Active site of malate dehydrogenase The active site of malate dehydrogenase is a hydrophobic cavity within the protein complex that has specific binding sites for the substrate and its coenzyme, NAD+. In its active state, MDH undergoes a conformational change that encloses the substrate to minimize solvent exposure and to position key residues in closer proximity to the substrate. The three residues in particular that comprise a catalytic triad are histidine (His-195), aspartate (Asp-168), both of which work together as a proton transfer system, and arginines (Arg-102, Arg-109, Arg-171), which secure the substrate. Mechanistically, malate dehydrogenase catalyzes the oxidation of the hydroxyl group of malate by utilizing NAD+ as an electron acceptor.
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Guerriero G, Sergeant K, Legay S. Hausman J-F, Cauchie H-M, Ahmad I, Siddiqui KS. 2018 Novel insights from comparative in silico analysis of green microalgae cellulases. Int. J. Mol. Sci. 19 (6), 1782. Several different kinds of cellulases are known, which differ structurally and mechanistically. Synonyms, derivatives, and specific enzymes associated with the name "cellulase" include endo-1,4-beta-D-glucanase (beta-1,4-glucanase, beta-1,4-endoglucan hydrolase, endoglucanase D, 1,4-(1,3,1,4)-beta-D-glucan 4-glucanohydrolase), carboxymethyl cellulase (CMCase), avicelase, celludextrinase, cellulase A, cellulosin AP, alkali cellulase, cellulase A 3, 9.5 cellulase, and pancellase SS. Enzymes that cleave lignin have occasionally been called cellulases, but this old usage is deprecated; they are lignin-modifying enzymes.
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NM-IIB is dephosphorylated by a myosin phosphatase. Detailed kinetic studies on NM-IIB show that this isoform of non-muscle myosin II has a slower actomyosin ATPase cycle relative to other myosin II isoforms, and that the markedly high affinity of NM-IIB head for ADP as well as the slow rate of ADP release can mechanistically explain affinity this finding. These data indicate that NM-IIB spends a large amount of its kinetic cycle in a configuration where it is strongly attached to actin. NM- IIB, along with the other non-muscle myosin isoforms IIA and IIC, play a role in cell-cell and cell-matrix adhesion, cell migration, cell polarity, and embryonic stem cell apoptosis.
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It has been shownAbsence of SN1 Involvement in the Solvolysis of Secondary Alkyl Compounds, T. J. Murphy, J. Chem. Educ.; 2009; 86(4) pp 519-24; (Article) doi: 10.1021/ed041p678 that except in uncommon (but predictable cases) primary and secondary substrates go exclusively by the SN2 mechanism while tertiary substrates go via the SN1 reaction. There are two factors which complicate determining the mechanism of nucleophilic substitution reactions at secondary carbons: 1) Many reactions studied are solvolysis reactions where a solvent molecule–often an alcohol, is the nucleophile. While still a second order reaction mechanistically, the reaction is kinetically first order as the concentration of the nucleophile–the solvent molecule, is effectively constant during the reaction.
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Other notions of agency have arisen in the field of economics/management, psychology and social cybernetics: In economics (contract theory): Economic agency is an internal instrumentality through which external influences operate mechanistically on action. Internal agency events are a reflection of the impact of external environments from which causal attributes are ignored, and the self-system is simply a repository and conduit for environmental forces. In psychology: The term of agency used in different fields of psychology with different meaning. It can refer to the ability of recognizing agents or attributing agency to objects based on simple perceptual cues or principles, for instance the principle of rationality, which holds that context-sensitive, goal-directed efficient actions are the crucial characteristics of agents.
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The target of lactacystin was subsequently found to be the proteasome on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995. The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery that helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease.
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This photoredox transformation was shown to be mechanistically distinct from another organocatalytic radical process termed singly-occupied molecular orbital (SOMO) catalysis. SOMO catalysis employs superstoichiometric ceric ammonium nitrate (CAN) to oxidize the catalytically-generated enamine to the corresponding radical cation, which can then add to a suitable coupling partner such as allyl silane. This type of mechanism is excluded for the photocatalytic alkylation reaction because whereas enamine radical cation was observed to cyclize onto pendant olefins and open cyclopropane radical clocks in SOMO catalysis, these structures were unreactive in the photoredox reaction. Diagram of Enantioselective Alkylation of Aldehydes via the synergistic combination of organo- and photoredox catalysis This transformation include alkylations with other classes of activated alkyl halides of synthetic interest.
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Erives' major work is on “regulatory grammars” for transcriptional enhancers underlying animal development and cancer diseases. Exploiting assemblies for animal genomes, Erives discovered complex gene regulatory codes underlie non- homologous subsets of mechanistically-equivalent enhancers. These codes are composed of a combinatorial “lexicon” of transcription factor (TF) binding sites, functional inflections of those binding sites (so-called “specialized sites” constrained for binding affinity and competition by multiple TFs), and complex site ordering (orientation and positional spacing of those sites). The relationship of these complex regulatory codes within a nucleosomal "regulatory reading frame" is a key goal. His lab’s work also elucidated how a mutational mechanism (microsatellite repeat slippage) plays a significant evolutionary role in functionally adjusting complex binding site arrangements that recruit poly-glutamine rich factors.
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Drugs or toxic chemicals are useful in killing pathogenic bacteria or tumor cells, and studying how they mechanistically develop tolerance to a wide range of drugs can improve anti-bacterial and cancer therapeutics. Pdr5p has a similar mechanism of actions and functions to human multidrug resistance protein, whose overexpression is shown to provide chemical tolerance to cancer cells. Studying Pdr5p and how it is regulated by Pdr1p in yeast can give insights into how multi drug resistance occurs in mammals. By using pdr1-3 and fusing the promoter of Pdr5p to genes that code for membrane proteins of interests, yeast membrane proteins such as Pdr5p, Yor1, and Drs2 can be expressed highly so that they can be efficiently cloned and purified for further studies.
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The HDDA reaction is a derivative of, and mechanistically related to, the classical Diels–Alder reaction. As described by Hoye and coworkers, the HDDA reaction can be viewed conceptually as a member of a series of pericyclic reactions with increasing unsaturation (by incremental removal of hydrogen pairs). The “hexadehydro” descriptor is derived from this interpretation, as the simplest HDDA reaction product (o-benzyne, 4 hydrogens) has 6 fewer hydrogen atoms than the simplest Diels–Alder reaction product (cyclohexene, 10 hydrogens). HDDA Figure 2 - DA- DHDA-THDA-HDDA comparison Formally, the hexadehydro Diels–Alder reaction describes only the formation of the benzyne, but this species is an unstable intermediate that reacts readily with a variety of trapping partners, including reaction solvents.
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During her postdoctoral studies at Rockefeller, Barson continued to follow up on her graduate work, exploring mechanistically the regulation of neuropeptides in the regulation of addiction and food consumption. Since previous studies showed that, just like the opioid enkephalin, galanin and orexin are also stimulated by dietary fats. Following up on this knowledge, Barson and her team explored which areas of the hypothalamic paraventricular nucleus (PVN) are specifically stimulated by high fat diets as well as exploring whether the ligands or receptors for galanin and orexin are over- expressed in these areas. Interestingly, Barson found strong overlap in galanin expressing cells and enkephalin expressing cells in the medial PVN of rats fed a high fat diet but not rats fed normal chow.
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The more sophisticated nuclear shell model is needed to mechanistically explain the route to the more energetically favorable outcome, in which one fission product is slightly smaller than the other. A theory of fission based on the shell model has been formulated by Maria Goeppert Mayer. The most common fission process is binary fission, and it produces the fission products noted above, at 95±15 and 135±15 u. However, the binary process happens merely because it is the most probable. In anywhere from 2 to 4 fissions per 1000 in a nuclear reactor, a process called ternary fission produces three positively charged fragments (plus neutrons) and the smallest of these may range from so small a charge and mass as a proton (Z = 1), to as large a fragment as argon (Z = 18).
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Mammalian cells with mutant ERCC1–XPF are moderately more sensitive than normal cells to agents (such as ionizing radiation) that cause double-stranded breaks in DNA. Particular pathways of both homologous recombination repair and non-homologous end-joining rely on ERCC1-XPF function. The relevant activity of ERCC1–XPF for both types of double-strand break repair is the ability to remove non-homologous 3′ single-stranded tails from DNA ends before rejoining. This activity is needed during a single-strand annealing subpathway of homologous recombination. Trimming of 3’ single- stranded tails is also needed in a mechanistically distinct subpathway of non- homologous end-joining, independent of the Ku proteins Homologous integration of DNA, an important technique for genetic manipulation, is dependent on the function of ERCC1-XPF in the host cell.
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The observations of tissue selectivity with tibolone have been theorized to be the result of metabolism, enzyme modulation (e.g., of estrogen sulfatase and estrogen sulfotransferase), and receptor modulation that vary in different target tissues. This selectivity differs mechanistically from that of selective estrogen receptor modulators (SERMs) such as tamoxifen, which produce their tissue selectivity via means of modulation of the ER. As such, to distinguish it from SERMs, tibolone has been variously described as a "selective tissue estrogenic activity regulator" (STEAR), "selective estrogen enzyme modulator" (SEEM), or "tissue-specific receptor and intracrine mediator" (TRIM). More encompassingly, tibolone has also been described as a "selective progestogen, estrogen, and androgen regulator" (SPEAR), which is meant to reflect the fact that it is tissue-selective and that it regulates effects not only of estrogens but of all three of the major sex hormone classes.
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The septic penetrating setal emboli (SPSE) hypothesis is the most probable mechanism of action for ETC exposure leading to MRLS. SPSE is believed to be a completely novel hypothesis, without precedent in biology or medicine. Reviewing the speed with which ETC dosing produced LFLs in controlled experiments and the barbed nature of ETC hairs (setae), and thereafter) intestinal blood vessel penetration by barbed ETC setal fragments, followed by their systemic distribution following cardiac output (SPSE) and then distant tissue penetration by these distributed fragments to tissues with reduced immune responses, i.e., the early- and late-term fetus, the eye, and the heart/pericardial space/fluid, followed by bacterial proliferation in the reduced immune response tissue (fetus, eye, pericardial fluid) would both quantitatively account for and mechanistically link all four MRLS syndromes, including most particularly the unique and unprecedented single-eye lesions.
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In this conception, neural processing begins with stimuli that activate sensory neurons, producing signals that propagate through chains of connections in the spinal cord and brain, giving rise eventually to activation of motor neurons and thereby to muscle contraction, i.e., to overt responses. Descartes believed that all of the behaviors of animals, and most of the behaviors of humans, could be explained in terms of stimulus-response circuits, although he also believed that higher cognitive functions such as language were not capable of being explained mechanistically. Charles Sherrington, in his influential 1906 book The Integrative Action of the Nervous System, developed the concept of stimulus- response mechanisms in much more detail, and Behaviorism, the school of thought that dominated Psychology through the middle of the 20th century, attempted to explain every aspect of human behavior in stimulus-response terms.
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Acyl-CoA dehydrogenases (ACADs) are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid β-oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrate Flavin adenine dinucleotide (FAD) is a required co-factor in addition to the presence of an active site glutamate in order for the enzyme to function. The following reaction is the oxidation of the fatty acid by FAD to afford an α,β-unsaturated fatty acid thioester of Coenzyme A: center ACADs can be categorized into three distinct groups based on their specificity for short-, medium-, or long-chain fatty acid acyl-CoA substrates. While different dehydrogenases target fatty acids of varying chain length, all types of ACADs are mechanistically similar.
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Sautrāntika, Encyclopædia Britannica It stated that each personal act "perfumes" the individual and leads to the planting of a "seed" that would later germinate as a good or bad karmic result. The Pudgalavada school of early Buddhism accepted the core premise of Buddhism that there is no attā (ātman, soul, self), but asserted that there is a "personal entity" (pudgala, puggala) that retains a karma balance sheet and is mechanistically involved in rebirth; this personal entity, stated Pudgalavada Buddhists, is neither different nor identical to the five aggregates (skandhas). This concept of personal entity to explain rebirth by Pudgalavada Buddhists was polemically attacked by Theravada Buddhists in the early 1st millennium CE. The personal entity concept was rejected by the mid-1st millennium CE Pali scholar Buddhaghosa, who attempted to explain rebirth mechanism with "rebirth- linking consciousness" (patisandhi).
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The problem of constructing practical algorithms to determine whether sentences with large numbers of propositional variables are tautologies is an area of contemporary research in the area of automated theorem proving. The method of truth tables illustrated above is provably correct – the truth table for a tautology will end in a column with only T, while the truth table for a sentence that is not a tautology will contain a row whose final column is F, and the valuation corresponding to that row is a valuation that does not satisfy the sentence being tested. This method for verifying tautologies is an effective procedure, which means that given unlimited computational resources it can always be used to mechanistically determine whether a sentence is a tautology. This means, in particular, the set of tautologies over a fixed finite or countable alphabet is a decidable set.
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Researchers have proposed that most common psychiatric and drug abuse disorders can be traced to a small number of dimensions of genetic riskMost psychiatric disorders share a small number of genetic risk factors, VCU study shows, Virginia Commonwealth University and reports show significant associations between specific genomic regions and psychiatric disorders. Though, to date only a few genetic lesions have been demonstrated to be mechanistically responsible for psychiatric conditions. For example, one reported finding suggests that in persons diagnosed as schizophrenic as well as in their relatives with chronic psychiatric illnesses, the gene that encodes phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation. The reasons for the relative lack of genetic understanding is because the links between genes and mental states defined as abnormal appear highly complex, involve extensive environmental influences and can be mediated in numerous different ways, for example by personality, temperament or life events.
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For example, the Orc4 subunit in S. pombe ORC contains several AT-hooks that preferentially bind AT-rich DNA, while in metazoan ORC the TFIIB-like domain of Orc6 is thought to perform a similar function. Metazoan Orc1 proteins also harbor a bromo-adjacent homology (BAH) domain that interacts with H4K20me2-nucleosomes. Particularly in mammalian cells, H4K20 methylation has been reported to be required for efficient replication initiation, and the Orc1-BAH domain facilitates ORC association with chromosomes and Epstein-Barr virus origin- dependent replication. Therefore, it is intriguing to speculate that both observations are mechanistically linked at least in a subset of metazoa, but this possibility needs to be further explored in future studies. In addition to the recognition of certain DNA or epigenetic features, ORC also associates directly or indirectly with several partner proteins that could aid initiator recruitment, including LRWD1, PHIP (or DCAF14), HMGA1a, among others.
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The mechanistic details of this reaction have been extensively explored by Crich’s laboratories.Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.Crich, D.; Chandrasekera, N. S. Angew. Chem. Int. Ed. 2004, 43, 5386. Low-temperature 1H, 13C, and 19F NMR spectroscopic investigations revealed that anomeric triflate 3 derived from 1 is the intermediate glycosyl donor. Moreover, the mechanism of glycosidic bond forming reaction (3→2) was examined thoroughly by the determination of kinetic isotopic effects (KIEs) and NMR spectroscopy. Consequently, the magnitude of KIEs indicated that the displacement of the triflate from 3 proceeded with the development of significant oxacarbenium ion character at the anomeric position. This might be rationalized either by (1) a dissociative mechanism involving the intermediacy of either a transient contact ion pair (CIP) 4 or a solvent-separated ion pair (SSIP) 5, or (2) a mechanistically variant transition state 7 (Scheme 2).
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Chronic low-grade inflammation (CLGI) plays a key role in metabolic deterioration in the obese population. Jak3 expression and activation provide protection against development of CLGI and associated health complications. Studies in rodent model show that loss of Jak3 results in increased body weight, basal systemic CLGI, compromised glycemic homeostasis, hyperinsulinemia, and early symptoms of liver steatosis. Lack of Jak3 also results in exaggerated symptoms of metabolic syndrome by western high-fat diet. Mechanistically, it is shown that Jak3 is essential for reduced expression and activation of toll like receptors (TLRs) in murine intestinal mucosa and human intestinal epithelial cells where Jak3 interacted with and activated p85, the regulatory sub-unit of the PI3K, through tyrosine phosphorylation of adapter protein insulin receptor substrate (IRS1). These interactions resulted in activation of PI3K-Akt axis, which was essential for reduced TLR expression and TLR associated NF-κB activation. Overall, Jak3 plays an essential role in promoting mucosal tolerance through suppressed expression and limiting activation of TLRs thereby preventing intestinal and systemic CLGI and associated obesity and MetS.
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