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472 Sentences With "activators"

How to use activators in a sentence? Find typical usage patterns (collocations)/phrases/context for "activators" and check conjugation/comparative form for "activators". Mastering all the usages of "activators" from sentence examples published by news publications.

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It would have also banned trigger activators, including bump stocks, designed to make weapons simulate automatic machine gun fire.
Telomerase has been of huge interest to the anti-aging community, and supplements claiming to be "telomerase activators" are circulating online.
Her phrases were torturously submitted to combination-permutation perversions by anonymous activators as part of their PLEASE CHANGE BELIEFS online project.
I would need to recruit people to be my surrogate brain activators, and have access to an fMRI scan for multiple days.
Cantley now refers to insulin and a closely related hormone, IGF-1 (insulinlike growth factor 1), as "the champion" activators of metabolic proteins linked to cancer.
Likewise, pro-gun organizations like the NRA and the National Shooting Sports Foundation (NSSF) have not returned our requests for comment on their official positions regarding trigger activators.
The measure would have banned assault weapons and high capacity magazines (more than 12 rounds), trigger activators that are designed to make weapons fire more rapidly, and silencers.
The goal is to get to a $1 billion perpetual fund backed by 1 million investors (or activators, as SheEO calls them) and invested in 10,000 women-led ventures.
Squint, cross your eyes, hold your breath, and turn on all your wishful-thinking activators, and you might be able to make an argument that it's about responsibility and unintentional harm.
But after I got the hang of layering base, powder, activators, bonders, and topcoats, I was seduced by the results: A glossy mani that lasted much longer than my favorite drugstore polish.
Watch this MinuteEarth video for an explanation of Turing's model: Scientists are still figuring out which specific dots and stripes develop from a Turing mechanism, and what the actual activators and inhibitors are in living creatures.
The measure, HB 961, looks to ban assault weapons -- defined as semi-automatic rifles and pistols -- high-capacity magazines (more than 12 rounds), trigger activators that are designed to make weapons fire more rapidly, and silencers.
Open now through March 31, the exhibit features a series of black and white photographs of Turner's pieces by Dario Calmese, which explore the role of Black churches "as activators not only for imagination but as crucibles for the construction of self" within the African American community.
Alkaline activators are usually based on sodium hydroxide. Some cosolvents double as activators. Amine activators, alkalines weaker than inorganic hydroxides, are favored when the substrate could be corroded by strong acids or bases. Surfactants assist with wetting the surface, increasing the area of where the solvent can penetrate the paint layer.
12 (6): 1453-1465. doi:10.1016/S1097-2765(03)00488-X “General Translational Repression by Activators of mRNA Decapping”(2005) Coller and Parker singled out activators for decapping mechanisms in this study. These decapping activators inhibit translation and stimulate the formation of P bodies. Using staining techniques to identify the activity of decapping activators, they were successfully able to conclude that there is a mechanism which signals mRNAs for decapping and therefore restricts mRNAs from going through translation.
PRPP and ATP are also allosteric activators of orotate synthesis.
Plant activators are compounds that activate a plant's immune system in response to invasion by pathogens. They play a crucial role in crop survival. Unlike pesticides, plant activators are not pathogen specific and are not affected by drug resistance, making them ideal for use in agriculture. Wet- rice farmers across East Asia use plant activators as a sustainable means to enhance crop health.
FibrinolysisPlasminogen activators are serine proteases that catalyze the activation of plasmin via proteolytic cleavage of its zymogen form plasminogen. Plasmin is an important factor in fibrinolysis, the breakdown of fibrin polymers formed during blood clotting. There are two main plasminogen activators: urokinase (uPA) and tissue plasminogen activator (tPA). Tissue plasminogen activators are used to treat medical conditions related to blood clotting including embolic or thrombotic stroke, myocardial infarction, and pulmonary embolism.
Tanning activators are chemicals that increase the effect of UV-radiation on the human skin.
Some allosteric activators are referred to as "essential", or "obligate" activators, in the sense that in their absence, the activity of their target enzyme activity is very low or negligible, as is the case with N-acetylglutamate's activity on carbamoyl phosphate synthetase I, for example.
Plasminogen activators are inhibited by plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, and protein C inhibitor.
For blockers and activators of voltage gated potassium channels see: potassium channel blocker and potassium channel opener.
For this reason, doubt has been cast on the feasibility of AMPAR activators for use in medicine. However, low doses of AMPAR activators may nonetheless be useful, and AMPAR PAMs, which, unlike agonists, show selectivity for AMPAR subpopulations of different subunit compositions, may hold greater potential for medical applications.
In context of phosphors and scintillators, dopants are better known as activators, and are used to enhance the luminescence process.
Proteins with no homology to the cyclin family can be direct activators of CDKs. One family of such activators is the RINGO/Speedy family, which was originally discovered in Xenopus. All five members discovered so far directly activate Cdk1 and Cdk2, but the RINGO/Speedy-CDK2 complex recognizes different substrates than cyclin A-CDK2 complex.
Domains in the LicR/CelR family of transcriptional activators show C-terminal domains exhibiting weak sequence similarity to IIBGat and IIAGat.
1H-Tetrazole and 5-(benzylthio)-1H-tetrazole (BTT) are widely used as acidic activators of the coupling reaction in oligonucleotide synthesis.
These are in most telemanipulators, which use the surgeon's activators on one side to control the "effector" on the other side.
The activation of plant responses is often associated with arrested growth and reductions in yield, for reasons that remain unclear. The molecular mechanisms governing plant activators are largely unknown. Screening can distinguish compounds that independently induce immune responses from those that do so exclusively in the presence of some pathogen. Independent activators can be toxic to cells.
These activators can be introduced into the system through attachment to dCas9 or to the sgRNA. Some researchers have noted that the extent of transcriptional upregulation can be modulated by using multiple sites for activator attachment in one experiment and by using different variations and combinations of activators at once in a given experiment or sample.
Other viruses have been reported to target upstream activators of pattern recognition proteins, antagonizing upstream proteins that removed inhibitory post-translational modifications.
In addition, protease nexin acts as an inhibitor of tPA and urokinase. PAI-1, however, is the main inhibitor of the plasminogen activators.
Activated MMP7 activates MMP2 and MMP9 zymogens, and mediates the proteolytic process of the precursors of tumor necrosis factors and urokinase plasminogen activators.
Assembly is known to occur in at least three distinct rate-determining steps. The products of these steps have been found, though specific subunit compositions have not been determined. Synthesis and assembly of COX subunits I, II, and III are facilitated by translational activators, which interact with the 5’ untranslated regions of mitochondrial mRNA transcripts. Translational activators are encoded in the nucleus.
GIRK channel inhibitors may serve to treat addictions to cocaine, opioids, cannabinoids, and ethanol while GIRK channel activators may serve to treat withdrawal symptoms.
Soluble guanylate cyclase (sGC) is the intracellular receptor for NO. , the sGC activators cinaciguat and riociguat were undergoing clinical trials for the treatment of PAH.
Nonetheless, there is a great deal of redundancy among the family members. Mouse embryos lacking E2F1, E2F2, and one of the E2F3 isoforms, can develop normally when either E2F3a or E2F3b, is expressed. The E2F family is generally split by function into two groups: transcription activators and repressors. Activators such as E2F1, E2F2, E2F3a promote and help carryout the cell cycle, while repressors inhibit the cell cycle.
Radium emanation activators, apparatuses that would apply radium emanation to water, started being produced and marketed. Scientifically constructed emanators were sold to hospitals, universities, and independent researchers. Certain companies advertised that they would only give them out to others on a medical prescription and would guarantee the strength of radium in each dose. Many products which imitated emanation activators were more broadly marketed to the public.
The consumption of bleach activators in 2002 was approximately 105,000 tonnes.G. Reinhardt, To Bleach or Not to Bleach – New Oxygen-Based Bleach Technology, in 5th World Conference on Detergents: Reinventing the Industry: Opportunities and Challenges, edit. A. Cahn, AOCS Publishing, 2003, . Consumption, however, is stagnant or declining due to cost pressures on detergents and the advance of liquid detergent formulations (which contain no bleach and bleach activators).
Another function of IL-25 is the activation of natural lymphoid cells 2 (ILC2). IL-25 and IL-33 are the most potent activators of ILC2.
Eventually, blood clots are reorganised and resorbed by a process termed fibrinolysis. The main enzyme responsible for this process (plasmin) is regulated by various activators and inhibitors.
The use of accelerators and activators lowers the activation energy of vulcanization reaction to 80-125kJ/mole from 210kJ/mole which is necessary if we use sulfur alone. Accelerators and activators break sulfur chains. Accelerated sulfur vulcanization systems require only 5-15 sulfur atoms per cross-link as compared to 40-45 S atoms/crosslink for a non-accelerated sulfur vulcanization. There are many accelerators available for the vulcanization of rubber.
All peroxide-based bleaches release hydrogen peroxide when dissolved in water. Peroxide bleaches are often used along with bleach activators, such as tetraacetylethylenediamine (TAED) or sodium nonanoyloxybenzenesulfonate (NOBS).
In the Lubrication Equipment Division (LED), Graco produces automatic lubrication equipment, vehicle lubrication maintenance and repair equipment, and a variety of activators and switches for the lubrication process.
As disordered telomerase function is a feature of almost all cancers, there is an unproven, but theoretical risk of oncogene-mediated cancer promotion through the use of telomerase activators.
The TFs binding sites are physical DNA sites recognized by transcription factors within a genome, including enhancer, upstream activator (UAS) and operator sites that may bind repressors or activators.
For genes with multiple regulatory sequences, the rate of transcription is the product of all of the elements combined. Binding of activators and repressors to multiple regulatory sequences has a cooperative effect on transcription initiation. Although all organisms use both transcriptional activators and repressors, eukaryotic genes are said to be 'default off', whereas prokaryotic genes are 'default on'. The core promoter of eukaryotic genes typically requires additional activation by promoter elements for expression to occur.
Activators consist of various metal salts, fatty acids, as well as nitrogen-containing bases, the most important these being zinc oxide. Zinc actives many accelerants by coordination, for example causing thiuram to convert into ziram. Zinc also coordinates to the sulfur-chains of sulfurating agents, changing the most likely bond to break during cross-link formation. Ultimately, activators promote the efficient use of sulfur to give a high density of cross-links.
Three strategies have emerged so far: excitation of spectrally separated fluorophores using an emission beamsplitter, using of multiple activators/reporters in STORM mode and ratiometric imaging of spectrally close fluorophores.
The SAM domain of p63 is thought to be imperative for protein-protein interactions, while the TI domain may play a role in the repression of other isoforms of p63. Recent work has shown that mutations within these domains lead to repression of other known transcriptional activators of epidermal differentiation. These transcription activators include: GRHL3, HOPX, PRDM1, KLF4, and ZNF750. Most notably, Hay-Wells-type p63 mutations cause irregular repression of the genes that encode for ZNF750.
Heat shock factors (HSF) are transcriptional activators of heat shock genes. These activators bind specifically to Heat Shock sequence Elements (HSE) throughout the genome whose consensus-sequence is a tandem array of three oppositely oriented "AGAAN" motifs or a degenerate version thereof. Under non-stressed conditions, Drosophila HSF is a nuclear-localized unbound monomer, whereas heat shock activation results in trimerization and binding to the HSE. The Heat Shock sequence Element is highly conserved from yeast to humans.
TRPV1 is a nonselective cation channel that may be activated by a wide variety of exogenous and endogenous physical and chemical stimuli. The best-known activators of TRPV1 are: temperature greater than ; acidic conditions; capsaicin (the irritating compound in hot chili peppers); and allyl isothiocyanate, the pungent compound in mustard and wasabi. The activation of TRPV1 leads to a painful, burning sensation. Its endogenous activators include: low pH (acidic conditions), the endocannabinoid anandamide, N-oleyl-dopamine, and N-arachidonoyl-dopamine.
These complexes include SAGA (Spt/Ada/Gcn5L acetyltransferase), PCAF, ADA (transcriptional adaptor), TFIID (transcription factor II D), TFTC (TBP-free TAF-containing complex), and NuA3/NuA4 (nucleosomal acetyltransferases of H3 and H4). These complexes modulate HAT specificity by bringing HATs to their target genes where they can then acetylate nucleosomal histones. Some HAT transcriptional co-activators contain a bromodomain, a 110-amino acid module that recognizes acetylated lysine residues and is functionally linked to the co-activators in the regulation of transcription.
In general, CAPP expression is controlled by an autoregulatory translational mechanism and with the developmental regulation of CAPP subunits (Janssens & Goris, 2001). Ceramide is the defining activator of CAPP while other activators include theophylline and sodium selenate. Mechanisms for their modes of activation are unknown and more research is needed to explore and identify new CAPP activators. I1PP2A and I2PP2A inhibit all possible forms of CAPP by associating with the catalytic subunit using their C-terminal domains (Li, Makkinje, & Damuni, 1996).
Other transcription factors are already in the nucleus, and are modified to enable the interaction with partner transcription factors. Some post-translational modifications known to regulate the functional state of transcription factors are phosphorylation, acetylation, SUMOylation and ubiquitylation. Transcription factors can be divided in two main categories: activators and repressors. While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions.
When activated, these receptors become associated with other activators and initiate gene transcription. TRs are also involved in cell viability, and are believed to have other non-genomic affects that are currently being investigated.
Cytokinetics, Inc. is a publicly traded biopharmaceutical company based in South San Francisco, California, that develops muscle activators and muscle inhibitors as potential treatments for people with diseases characterized by impaired or declining muscle function.
Since the cargo-linkage mechanism of this complex is believed to be phosphporylation-dependent, phosphorylation by JNK kinase can release its own upstream activators from the scaffold, thus driving a strong local positive feedback loop.
E2F1, E2F2, and E2F3A are the three canonical activators of the E2F family of transcription factors. During G2, cyclin F targets all three activator E2Fs for degradation, thereby turning off a main cell-cycle transcriptional engine.
Temperature sensors are installed outside to sense the same temperature conditions that the surface that the snow melting system will experience. Other activators, such as manual timers or switches can be installed in a convenient location.
Strategies for multicolor localization microscopy. Left: spectral separation. Center: multiple activators (STORM). Right: Ratiometric imaging The peculiar photophysical properties of the fluorophores employed in PALM/STORM super resolution imaging pose both constraints and opportunities for multicolor imaging.
In the absence of NACA, proteins lacking signal peptides can be mis-translocated into the endoplasmic reticulum. The NACA protein is expressed in bone during development and acts as a transcriptional coactivator in conjunction with acidic activators.
Like many other transcription factors, STATs are capable of recruiting co-activators such as CBP and p300, and these co-activators increase the rate of transcription of target genes. The coactivators are able to do this by making genes on DNA more accessible to STATs and by recruiting proteins needed for transcription of genes. The interaction between STATs and coactivators occurs through the transactivation domains (TADs) of STATs. The TADs on STATs can also interact with histone acetyltransferases (HATs); these HATs add acetyl groups to lysine residues on proteins associated with DNA called histones.
A transcriptional activator is a protein (transcription factor) that increases gene transcription of a gene or set of genes. Most activators are DNA-binding proteins that bind to enhancers or promoter-proximal elements. Most activators function by binding sequence-specifically to a DNA site located in or near a promoter and making protein–protein interactions with the general transcription machinery (RNA polymerase and general transcription factors), thereby facilitating the binding of the general transcription machinery to the promoter. The DNA site bound by the activator is referred to as an "activator site".
Among the latter are the TAF proteins. Different TAFs are predicted to mediate the function of distinct transcriptional activators for a variety of gene promoters and RNA polymerases. TAF12 interacts directly with TBP as well as with TAF2I.
ZFP-TFs, consisting of activators and repressors are transcription factors composed of a zinc finger protein domain and any of a variety of transcription-factor effector-domains which exert their modulatory effect around any sequence to which the ZFP domain binds.
The down-regulation of ZNF750 has been shown to hinder the expression of the other before mentioned differentiation-activators such as HOPX, PRDM1, KLF4, and GRHL3. In contrast, recapitulating the expression of ZNF750 leads to significant rescue of normal epidermal differentiation.
Upon engaging the transcription factors LEF1, TCF1, TCF2 or TCF3, β-catenin forces them to disengage their previous partners: Groucho proteins. Unlike Groucho, that recruit transcriptional repressors (e.g. histone-lysine methyltransferases), beta-catenin will bind transcriptional activators, switching on target genes.
Recent studies also show that mutations in Sos1 can cause Noonan syndrome and hereditary gingival fibromatosis type 1. Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes. activators of the MAP kinase pathway.
Lorlatinib must not be combined with strong inducers (i.e. activators) of the liver enzymes CYP3A4/5 if it can be avoided, as serious cases of liver toxicity have been observed under combination with the CYP3A4/5 inducer rifampicin. on Lorbrena.
One of the earliest and most well known form of sensory substitution devices was Paul Bach-y-Rita's TVSS that converted the image from a video camera into a tactile image and coupled it to the tactile receptors on the back of his blind subject. Recently, several new systems have been developed that interface the tactile image to tactile receptors on different areas of the body such as the on the chest, brow, fingertip, abdomen, and forehead. The tactile image is produced by hundreds of activators placed on the person. The activators are solenoids of one millimeter diameter.
EAAT2/GLT-1, being the most abundant subtype of glutamate transporter in the CNS, plays a key role in regulation of glutamate neurotransmission. Dysfunction of EAAT2 has been correlated with various pathologies such as traumatic brain injury, stroke, Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, among others. Therefore, activators of the function or enhancers of the expression of EAAT2/GLT-1 could serve as a potential therapy for these conditions. Translational activators of EAAT2/GLT-1, such as ceftriaxone and LDN/OSU-0212320, have been described to have significant protective effects in animal models of ALS and epilepsy.
In addition, pharmacological activators of the activity of EAAT2/GLT-1 have been explored for decades and are currently emerging as promising tools for neuroprotection, having potential advantages over expression activators. DL- TBOA, WAY-213,613, and dihydrokainic acid are known inhibitors of the protein, and function as excitotoxins. They can be considered a novel class of nerve agent toxins, inducing toxic levels of glutamate through transport inhibition in a manner analogous to the effect of sarin on cholinesterase. Antidotes for such a poisoning have never been formally tested for efficacy and are not readily available for medical use.
Chemical compounds can bind to troponin C to act as troponin activators (calcium sensitizers) or troponin inhibitors (calcium desensitizers). There are already multiple troponin activators that bind to fast skeletal troponin C, of which tirasemtiv has been tested in multiple clinical trials. In contrast, there are no known compounds that bind with high affinity to cardiac troponin C. The calcium sensitizer, levosimendan, is purported to bind to troponin C, but only weak or inconsistent binding has been detected, precluding any structure determination. In contrast, levosimendan inhibits type 3 phosphodiesterase with nanomolar affinity, so its biological target is controversial.
Some compounds have been identified to bind cNTnC with low affinity and act as troponin activators: DFBP-O (a structural analog of levosimendan), 4-(4-(2,5-dimethylphenyl)-1-piperazinyl)-3-pyridinamine (NCI147866), and bepridil. The calmodulin antagonist, W7, has also been found to bind to cNTnC to act as a troponin inhibitor. All of these compounds bind to the hydrophobic patch in the open conformation of cNTnC, with troponin activators promoting interaction with the cTnI switch peptide and troponin inhibitors destabilizing the interaction. A number of compounds can also bind to cCTnC with low affinity: EMD 57033, resveratrol, bepridil, and EGCG.
See: Transcriptional Activator, Transcription Factor Transcriptional Activators are protein domains or whole proteins linked to dCas9 or sgRNAs that assist in the recruitment of important co-factors as well as RNA Polymerase for transcription of the gene(s) targeted by the system. In order for a protein to be made from the gene that encodes it, RNA polymerase must make RNA from the DNA template of the gene during a process called transcription. Transcriptional activators have a DNA binding domain and a domain for activation of transcription. The activation domain can recruit general transcription factors or RNA polymerase to the gene sequence.
Ruxolitinib is a janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.
Simplified Representation of Neurospora Circadian Clock. WC-1 and WC-2 (WCC) act as positive activators of frq transcription. FRQ protein binds to an RNA helicase, FRH, and to CK1 forming a complex. This complex interacts with WCC, promoting phosphorylation of WCC.
A mouse model of Dravet syndrome has been treated using a variant of CRISPR that relies on a guide RNA and a dead Cas9 (dCas9) protein to recruit transcriptional activators to the promoter region of the sodium channel gene Scn1a in interneurons.
Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products, succinyl CoA and NADH. A high energy charge in the cell will also be inhibitive. ADP and calcium ions are allosteric activators of the enzyme.
Activators regenerated by electron transfer (ARGET) employs non-radical forming reducing agents for regeneration of CuI. A good reducing agent (e.g. hydrazine, phenols, sugars, ascorbic acid) should only react with CuII and not with radicals or other reagents in the reaction mixture.
The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010].
The etymology stems from ligare, which means 'to bind'. Ligand binding to a receptor protein alters the conformation by affecting the three-dimensional shape orientation. The conformation of a receptor protein composes the functional state. Ligands include substrates, inhibitors, activators, signaling lipids, and neurotransmitters.
Kinetic scheme for reversible enzyme inhibitors. Enzyme inhibitors are molecules that reduce or abolish enzyme activity, while enzyme activators are molecules that increase the catalytic rate of enzymes. These interactions can be either reversible (i.e., removal of the inhibitor restores enzyme activity) or irreversible (i.e.
Positive regulation of L-arabinose operon via dimeric AraC and CAP/cAMP Expression of the araBAD operon is activated in the absence of glucose and in the presence of arabinose. When arabinose is present, both AraC and CAP work together and function as activators.
In reality, most genes are hundreds of times larger. An internal control region is a sequence of DNA located with the coding region of eukaryotic genes that binds regulatory elements such as activators or repressors. This region can recruit RNA Polymerase or contribute to splicing.
EBNA2 has an acidic activation domain, which can interact with many different general transcription factors and co- activators. Regulation of transcription initiation and elongation by EBNA 2 is done part through cyclin-dependent kinase 9 (CDK9) dependent phosphorylation of the RNA polymerase C-terminal domain.
Activation of EP4 stimulates duodenum epithelial cells to secrete bicarbonate (HCO3-) in mice and humans; this response neutralizes the acidic fluid flowing from the stomach thereby contributing to the process of intestinal ulcer healing. Activators of this receptor therefore may useful as anti-ulcer drugs.
Differential modulation of the active site environment of CAXII by cationic quantum dots and polylysine helps design CAXII specific activators and inhibitors of the enzyme. CAXII specific inhibition provides a tool to interfere with cell proliferation, resulting in cell apoptosis in T-cell lymphomas.
Activation domains can also function by facilitating transcription by stalled RNA polymerases, and in eukaryotes can act to move nucleosomes on the DNA or modify histones to increase gene expression.Ma, J. (August 2011). Transcriptional activators and activation mechanisms. Protein and Cell, 2(11), 879-888.
Many metal halides are precatalysts for olefin polymerization, see Kaminsky catalyst and Ziegler-Natta catalysis. The precatalysts, e.g. titanium trichloride, are activated by organoaluminium compounds, which function as catalyst activators. Metal oxides are often classified as catalysts, but in fact are almost always precatalysts.
Activated Plk activates cdc25. Activation of Cdc25 and inactivation of Wee1/Myt1 lead to further activation of Cyclin-B1/CDK1. Also shown is the putative role of cyclin-A/CDK2 and Cdc25A as initial activators of the feedback loop, discussed in a later section.
This occurs when Whi5 is phosphorylated by Cdc8 which is a G1/S Cdk. Suppression of histone gene expression outside of S phases is dependent on Hir proteins which form inactive chromatin structure at the locus of histone genes, causing transcriptional activators to be blocked.
When different genes were targeted by dCas9, they all showed significantly greater expression with dCas9-VPR than with dCas9-VP64. It has also been demonstrated that dCas9-VPR can be used to increase expression of multiple genes within the same cell by putting multiple sgRNAs into the same cell. dCas9-VPR has been used to activate the neurogenin 2 (link) and neurogenic differentiation 1 (link) genes, resulting in differentiation of induced pluripotent stem cells into induced neurons. A study comparing dCas9 activators found that the VPR, SAM, and Suntag activators worked best with dCas9 to increase gene expression in a variety of fruit fly, mouse, and human cell types.
Chromatin remodeling complexes in the dynamic regulation of transcription: In the presence of acetylated histones (HAT mediated) and absence of methylase (HMT) activity, chromatin is loosely packaged. Additional nucleosome repositioning by chromatin remodeler complex, SWI/SNF opens up DNA region where transcription machinery proteins, like RNA Pol II, transcription factors and co-activators bind to turn on gene transcription. In the absence of SWI/SNF, nucleosomes can not move farther and remain tightly aligned to one another. Additional methylation by HMT and deacetylation by HDAC proteins condenses DNA around histones and thus, make DNA unavailable for binding by RNA Pol II and other activators, leading to gene silencing.
Well-defined vanadium compounds do not appear as catalysts in any commercial process. However organovanadium species are clearly implicated as catalysts for the production of butadiene-based rubbers. These catalysts are generated in situ by treating soluble coordination complexes such as vanadium(III) acetylacetonate with organoaluminium activators.
However, other molecules also act as activators. Norrin and R-Spondin2 activate Wnt signaling in the absence of Wnt ligand. Interactions between Wnt signaling pathways also regulate Wnt signaling. As previously mentioned, the Wnt/calcium pathway can inhibit TCF/β-catenin, preventing canonical Wnt pathway signaling.
Others enhance resistance only in the presence of pathogens. In 2012, five activators that protected against Pseudomonas bacteria by priming immune response without directly activating defense genes. The compounds inhibit two enzymes that inactivate the defense hormone salicylic acid (SA glucosyltransferases or SAGTs), providing enhanced disease resistance.
Activating and repressing sites overlap in sequence. Eve is only expressed in a narrow stripe of cells that contain high concentrations of the activators and low concentration of the repressors for this enhancer sequence. Other enhancer regions drive eve expression in 6 other stripes in the embryo.
Mechano/sono-ATRP uses mechanical forces, typically ultrasonic agitation, as an external stimulus to induce the (re)generation of activators in ATRP. Esser-Kahn, et al. demonstrated the first example of mechanoATRP using the piezoelectricity of barium titanate to reduce Cu(II) species. Matyjaszewski, et al.
Research conducted on mice suggests that stabilizing HIF using an HIF prolyl-hydroxylase inhibitor enhances hippocampal memory, likely by increasing erythropoietin expression. HIF pathway activators such as ML-228 may have neuroprotective effects and are of interest as potential treatments for stroke and spinal cord injury.
Several studies have indicated that the proteolytic activity of APC contributes to the observed cytoprotective properties of APC, but variants that are proteolytically inactive also are able to regulate formation of PAR-activators thrombin and factor Xa and express cytoprotective properties in vitro and in vivo.
FAM89A contains a conserved leucine-rich adapter protein domain (LURAP) called PF14854, located at amino acid positions 84-122. The LURAP superfamily of proteins are activators of the canonical NF-κB pathway, involved in promoting antigen presentation in dendritic cells and the production of pro-inflammatory cytokines.
Bleach activation is also known as perhydrolysis. Persalts are inorganic salts that are used as hydrogen peroxide carriers (examples include sodium percarbonate and sodium perborate). Persalts and bleach activators are included together in powder laundry detergents that contain bleach. In the wash, both compounds dissolve in the water.
Enhancers can facilitate highly cooperative action of several transcription factors (which constitute enhanceosomes). Remote enhancers allow transcription regulation at a distance. Insulators situated between enhancers and promoters help define the genes that an enhancer can or cannot influence. Eukaryotic transcriptional activators have separate DNA-binding and activating functions.
Briscoe was educated at the University of Warwick and King's College London where he was awarded a PhD in 1996 for research on Janus kinases (JAKS), Signal Transducers and Activators of Transcriptions (STATs) and signal transduction in response to the interferons and Interleukin-6 supervised by Ian M. Kerr.
Due to the unknown structure and mechanism of MAO, alternatives have been found in tetrakisperfluoroarylborate salts such as tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anion (BArF4−). Such well- defined activators may be used stoichiometrically, whereas MAO is typically present in a reaction mixture in approximately hundredfold to thousandfold excess.
Certificates are issued at point intervals. Other variants of this radio-sport along the same lines exist, for example WWFF (World Wide Flora and Fauna in Amateur Radio) where activators set up a station in a nature area and chasers contact an operator who is in the nature area.
The cure package consists of various reagents that modify the kinetics and chemistry of crosslinking. These include accelerants, activators, retarders and inhibitors. Note that these are merely the additives used for vulcanization and that other compounds may also be added to the rubber, such as fillers or polymer stabilizers.
E2F is a group of genes that encodes a family of transcription factors (TF) in higher eukaryotes. Three of them are activators: E2F1, 2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8. All of them are involved in the cell cycle regulation and synthesis of DNA in mammalian cells.
Dock6 ( _D_ edicator _o_ f _c_ yto _k_ inesis 6), also known as Zir1 is a large (~200 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins.
Fibroblast growth factor receptor substrate 3 is a protein that in humans is encoded by the FRS3 gene. The protein encoded by this gene is a substrate for the fibroblast growth factor receptor. It is found in peripheral plasma membrane and functions in linking FGF receptor stimulation to activators of Ras.
An alternative method for lowering dissociation temperatures is doping with activators. This strategy has been used for aluminium hydride, but the complex synthesis makes the approach unattractive. Proposed hydrides for use in a hydrogen economy include simple hydrides of magnesiumCNRS Institut Neel H2 Storage. Neel.cnrs.fr. Retrieved on 2012-01-08.
The toxins mezerein and daphnetoxin are both present in the genus Daphne. Daphnetoxin has a structure similar to mezerein, with the phenyl-pentadienoyl component (top left of the mezerein structural diagram) missing. They are both PKC activators but with a different selectivity: mezerein exhibits antileukemic properties while daphnetoxin does not.
PAK1 contains an autoinhibitory domain that suppresses the catalytic activity of its kinase domain. PAK1 activators relieve this autoinhibition and initiate conformational rearrangements and autophosphorylation events leading to kinase activation. IPA-3 (1,1′-disulfanediyldinaphthalen-2-ol) is a small molecule allosteric inhibitor of PAK1. Preactivated PAK1 is resistant to IPA-3.
There are three FOXM1 isoforms, A, B and C. Isoform FOXM1A has been shown to be a gene transcriptional repressor whereas the remaining isoforms (B and C) are both transcriptional activators. Hence, it is not surprising that FOXM1B and C isoforms have been found to be upregulated in human cancers.
The 1,3/1,6-ß-D-glucan in this complex are macromolecules consisting solely of the carbohydrate glucose. There are many varieties of glucan. The main difference lies in the effectiveness and efficiency of these glucans. According to the most recent experimental studies, it is one of the most effective activators.
DOCK8 ( _D_ edicator _o_ f _c_ yto _k_ inesis 8), also known as Zir3, is a large (~190 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins.
The EDF1 gene encodes a protein that acts as a transcriptional coactivator by interconnecting the general transcription factor TATA element-binding protein (TBP) and gene-specific activators. TFIID and human mediator coactivator (THRAP3) complexes (mediator complex, plus THRAP3 protein) assemble cooperatively on promoter DNA, from which they become part of the RNAPII holoenzyme.
They do not trigger a response of change in apoptosis and therefore have no chromatin margination or cleave poly ADP-ribose polymerase (PARP). Instead, the phenotype of the mitochondria is changed using primarily erastin or RSL3. Iron is also a necessity for these activators. They therefore can be inhibited by iron chelators.
Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock11 activates the small G protein Cdc42.
The sulfonylurea receptors (SUR), involved in insulin secretion, neuronal function, and muscle function, are also part of this family of proteins. Mutations in SUR proteins are a potential cause of Neonatal diabetes mellitus. SUR is also the binding site for drugs such as sulfonylureas and potassium-channel openers activators such as diazoxide.
The SQUAMOSA promoter binding protein-like (SBP or SPL) family of transcription factors are defined by a plant-specific DNA-binding domain. The founding member of the family was identified based on its specific in vitro binding to the promoter of the snapdragon SQUAMOSA gene. SBP proteins are thought to be transcriptional activators.
Activators generated by electron transfer uses a reducing agent unable to initiate new chains (instead of organic radicals) as regenerator for the low- valent metal. Examples are metallic copper, tin(II), ascorbic acid, or triethylamine. It allows for lower concentrations of transition metals, and may also be possible in aqueous or dispersed media.
In 2004, Sinclair, along with serial entrepreneur Andrew Perlman, Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel, founded Sirtris Pharmaceuticals. Sirtris was focused on developing Sinclair's research into activators of sirtuins, work that began in the Guarente lab. The company was specifically focused on resveratrol formulations and derivatives as activators of the SIRT1 enzyme; Sinclair became known for making statements about resveratrol like: “(It's) as close to a miraculous molecule as you can find.... One hundred years from now, people will maybe be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer.” Most of the anti-aging field was more cautious, especially with regard to what else resveratrol might do in the body and its lack of bioavailability.
Furthermore, IP(-/-) mice on a high salt diet develop significantly higher levels of hypertension, cardiac fibrosis, and cardiac hypertrophy than control mice. The vasodilating and, perhaps, platelet-inhibiting effects of IP receptors likely underlie its ability suppress hypertension and protect tissues such as the heart in this model as well as the heart, brain, and gastrointestinal tract in various animal models of ischemic injury. Indeed, IP agonists are used to treat patients pathological vasoconstriction diseases. The injection of IP activators into the skin of rodents increases local capillary permeability and swelling; IP(-/-) mice fail to show this increased capillary permeability and swelling in response not only to IP activators but also in a model of carrageenan- or bradykinin-induced paw edema.
Nektarios Tavernarakis has contributed to the elucidation of the molecular mechanisms of necrotic cell death and neurodegeneration, the interplay between cellular metabolism and ageing, the mechanisms of sensory transduction and integration by the nervous system. He has also contributed towards the development of novel genetic tools for biomedical research, including an RNA interference (RNAi) method that allows efficient knockdown of neuronal genes. His PhD Thesis research focused on the expression and function of key stress response transcriptional activators in the yeast Saccharomyces cerevisiae, and provided original insights on the regulation of these activators by nutrient limitation, and the role of DNA in determining interactions between transcription factors and co-factors. His laboratory at IMBB was the first to commence Caenorhabditis elegans research in Greece.
Sirt6 deacetylation activity can be stimulated by high concentrations (several hundred micromolar) of fatty acids, and more potently by a first series of synthetic activators based on a pyrrolo[1,2-a]quinoxaline scaffold. Crystal structures of Sirt6/activator complexes show that the compounds exploit a SIRT6 specific pocket in the enzyme's substrate acyl binding channel.
Barouch has also worked on immunologic strategies to cure HIV infection. In 2016 and 2018, he demonstrated the potential of combining therapeutic vaccines or broadly neutralizing antibodies with immune activators, also known as the "shock and kill" strategy. Barouch has also discussed his research and has commented on the research of others in the media.
Hypoprolactinemia can result from autoimmune disease, hypopituitarism, growth hormone deficiency, hypothyroidism, excessive dopamine action in the tuberoinfundibular pathway and/or the anterior pituitary, and ingestion of drugs that activate the D2 receptor, such as direct D2 receptor agonists like bromocriptine and pergolide, and indirect D2 receptor activators like amphetamines (through the induction of dopamine release).
Cancer Biother. Radiopharm.32, 327–334 (2017). Expression of ETS1was increased in cancer tissues as compared with the expression in corresponding non-neoplastic tissues. Finally, USF is an upstream stimulating factor, which is involved in mediating recruitment of chromatin remodelling enzymes and interacting with co-activators and members of the transcription pre-initiation complex.
The full length of mature staphylokinase mRNA is 489bp. The first 27 amino acids code for a signal peptide which is cleaved off in the mature protein (mSak). There is little or no homology between the primary structure of Sak and other plasminogen activators. The natural variants of Sak are Sak42D, SakφC and SakSTAR.
Viral microRNAs play an important role in the regulation of gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host–virus interactions and pathogenesis of viral diseases. The expression of transcription activators by human herpesvirus-6 DNA is believed to be regulated by viral miRNA.
Pathogenic expansions have typically over 200 repeats and are methylated. This gene belongs to the AFF family of genes which currently has four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the nucleus and have a role as transcriptional activators with a positive action on RNA elongation.
The activation of ionic polymers, on the other hand, requires only 1-2 volts. They however need to maintain wetness, though some polymers have been developed as self-contained encapsulated activators which allows their use in dry environments. Ionic polymers also have a low electromechanical coupling. They are however ideal for bio-mimetic devices.
Active infections involve the linear dsDNA genome circularizing by end to end covalent linkages. This process was first reported for the herpes simplex virus. Once circularized, HHV-6 begins to express what are known as "immediate early" genes. These gene products are believed to be transcription activators and may be regulated by the expression of viral micro RNAs.
Dock9 ( _D_ edicator _o_ f _c_ yto _k_ inesis 9), also known as Zizimin1, is a large (~230 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors that function as activators of small G proteins. Dock9 activates the small G protein Cdc42.
Dock9 was discovered using an affinity proteomic approach designed to identify novel activators of the small G protein Cdc42 in fibroblasts. Subsequent northern blot analysis revealed that Dock9 is expressed primarily in the brain, heart, skeletal muscle, kidney, placenta and lung. Lower levels were detected in the colon, thymus, liver, small intestine and in leukocytes from peripheral blood.
This is an example of exon skipping. The intron upstream from exon 4 has a polypyrimidine tract that doesn't match the consensus sequence well, so that U2AF proteins bind poorly to it without assistance from splicing activators. This 3' splice acceptor site is therefore not used in males. Females, however, produce the splicing activator Transformer (Tra) (see below).
For example, LTBP-4 is reported to bind only to TGF-β1, thus, mutation in LTBP-4 can lead to TGF-β associated complications which are specific to tissues that predominantly involves TGF-β1. Moreover, the structural differences within the LAP's provide different latent TGF-β complexes which are selective but to specific stimuli generated by specific activators.
Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large (~240 kDa) protein involved in intracellular signalling networks that in humans is encoded by the DOCK10 gene. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors, which function as activators of small G proteins.
FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver- specific transcripts such as albumin and transthyretin, and they also interact with chromatin as a pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.
Eukaryotic genes also contain regulatory sequences beyond the core promoter. These cis-acting control elements bind transcriptional activators or repressors to increase or decrease transcription from the core promoter. Well-characterized regulatory elements include enhancers, silencers, and insulators. These regulatory sequences can be spread over a large genomic distance, sometimes located hundreds of kilobases from the core promoters.
There are thirteen kinds of mammalian phospholipase C that are classified into six isotypes (β, γ, δ, ε, ζ, η) according to structure. Each PLC has unique and overlapping controls over expression and subcellular distribution. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.
Pneumatic air muscle Joint actuators also face the challenge of being lightweight, yet powerful. Technologies used include pneumatic activators, hydraulic cylinders, and electronic servomotors. Elastic actuators are being investigated to simulate control of stiffness in human limbs and provide touch perception. The air muscle, braided pneumatic actuator or McKibben air muscle, is also used to enhance tactile feedback.
HES1 influences the maintenance of certain stem cells and progenitor cells. Specifically, HES1 influences the timing of differentiation by repressing bHLH activators, and determines binary cell fate. HES1 has been shown to play a large role in both the nervous, and digestive systems. HES1 has been shown to influence these two systems partially through the Notch signaling pathway.
This includes downregulation and desensitization of the GABAA receptor, reduced effects of allopregnanolone and other GABAA receptor activators (e.g., and benzodiazepines), and rebound or withdrawal effects upon falls in allopregnanolone levels. In addition, changes in allopregnanolone levels have been implicated in adverse neuropsychiatric effects associated with the menstrual cycle (e.g., dysphoria, depression, anxiety, irritability) and postpartum period (e.g.
CRISPR activation (CRISPRa) is one type of CRISPR tool that use modified versions of dCas9, a mutation of Cas9 without endonuclease activity, with added transcriptional activators on dCas9 or the guide RNAs (gRNAs). Like a standard CRISPR-Cas9 system, dCas9 activation systems rely on similar components such as Cas9 variants for modulation or modification of genes, gRNAs to guide Cas9 to intended targets, and vectors for introduction into cells. However, while a standard CRISPR-Cas9 system relies on creating breaks in DNA through the endonuclease activity of Cas9 and then manipulating DNA Repair mechanisms for gene editing, dCas9 activation systems are modified and employ transcriptional activators to increase expression of genes of interest. Such systems are usable for many purposes including but not limited to, genetic screens and overexpression of proteins of interest.
Coller, Jeff; Parker, Roy (23 September 2005). “General Translational Repression by Activators of mRNA Decapping”. Cell. 122 (6): 875-886. doi:10.1016/j.cell.2005.07.012 “Movement of Eukaryotic mRNAs between Polysomes and Cytoplasmic Processing Bodies”(2005) Throughout this paper, Parker and two other scientists, Brengues and Teixeira, demonstrated that mRNAs migrate between polysomes and cytoplasmic processing bodies as a form of mRNA packing.
In activators, E2F binding with pRB has been shown to mask the transactivation domain responsible for transcription activation. In repressors E2F4 and E2F5, pocket protein binding (more often p107 and p130 than pRB) mediates recruitment of repression complexes to silence target genes. E2F6, E2F7, and E2F8 do not have pocket protein binding sites and their mechanism for gene silencing is unclear.
The G-less cassette technique is used to determine promoter strength beyond basal levels of transcription (i.e. in the presence of transcription activators or transcription factors). For example, to measure the effects of a TATA box consensus sequence modification in Saccharomyces cerevisiae in the presence of TFIID, G-less cassettes were implemented to measure the relative strength of each promoter.
It is also administered intrapleurally to improve the drainage of complicated pleural effusions and empyemas. Urokinase is marketed as Kinlytic (formerly Abbokinase) and competes with recombinant tissue plasminogen activator (e.g., alteplase) as a thrombolytic drug. All plasminogen activators (urokinase, tPA) catalyze the production of plasmin, which in turn leads to the breakdown of the fibrin lattice structure in blood clots.
Members of the RAS subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation.
Protein kinases, many of which are regulated by autophosphorylation, are vital in controlling the cellular proliferation, differentiation, metabolism, migration and survival. Mutations in the genes encoding them or their potential activators or repressors can affect any number of functions within an organism. Phosphorylation is easily reversed by phosphatases. Therefore, it is an effective method of turning 'on' and 'off' kinase activity.
Dock7 ( _D_ edicator _o_ f _c_ yto _k_ inesis 7), also known as Zir2, is a large (~240 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock7 activates isoforms of the small G protein Rac.
Dock4, ( _D_ edicator _o_ f _c_ yto _k_ inesis 4) also known as DOCK4, is a large (~190 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock4 activates the small G proteins Rac and Rap1.
Clinicians Report 2012;5(3): 1-4. a)Can be used in total-etch, self-etch, and selective etch techniques; b)Can be used with light-cure, self-cure, and dual- cure materials (without the separate activators); c)Can be used for both direct and indirect substrates; d)Can bond to all dental substrates, such as dentin, enamel, metal, ceramic, porcelain, and zirconia.
Bleach activators are typically made up of two parts: the peroxy acid precursor and the leaving group; and are modified by altering these parts. The peroxy acid precursor affects the bleaching properties of the peroxy acid: determining the activity, selectivity, hydrophobic/hydrophilic balance and oxidation potential. The leaving group influences the solubility, perhydrolysis rate and storage stability of the activator.
NO also reduces pulmonary smooth muscle cell growth and antagonises platelet inhibition, factors which play a key role in the pathogenesis of PAH. In contrast to NO- and haem-independent sGC activators like cinaciguat, the sGC stimulator riociguat directly stimulates sGC activity independent of NO and also acts in synergy with NO to produce anti-aggregatory, anti-proliferative, and vasodilatory effects.
As early as in 1932, the saliva of the vampire bat (Desmodus rotundus) was known to lead to interference with the haemostatic mechanism of the host animal. In 1991, the DNA coding of four plasminogen activators present in the saliva of the vampire bat was completed. Of the four, recombinant D. rotundus salivary plasminogen activator alpha 1 (rDSPAα1; desmoteplase) was investigated further.
Dock5 ( _D_ edicator _o_ f _c_ yto _k_ inesis 5), also known as DOCK5, is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock5 is predicted to activate the small G protein Rac.
Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes () of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic.
Mission Control is CosmoBot's child-friendly version of a keyboard. It contains four large, pressure-sensitive buttons, called aFFx Activators, and incorporates a microphone. It also includes two USB ports for connection of gestural sensors. The therapist uses the GUI to assign a function to each button, such as indicating that depression of the red button will move CosmoBot forward.
Activators increase the penetration rate; for dichloromethane water is suitable, other choices are amines, strong acids or strong alkalis. The activator's role is to disrupt the molecular and intermolecular bonds in the paint film and assist with weakening this. Its composition depends on the character of the paint to be removed. Mineral acids are used for epoxy resins to hydrolyze their ether bonds.
This is important as if the bubble coalesce, minerals fall off their surface. The bubbles however should not be too stable as this prevents easy transportation and dewatering of the concentrate formed. The mechanism of these frothers is not completely known and further research into their mechanisms is being performed. Depressants and activators are used to selectively separate one mineral from another.
Today, manufactured wings for the Airbus A380 aircraft leave Mostyn on the ship Ville de Bordeaux, after travelling down the River Dee by barge from the Airbus wing factory at Broughton, Flintshire. See Itinéraire à Grand Gabarit for more details of the transportation. Mostyn's port area is home to the headquarters of Warwick International Group Limited, manufacturers of bleach activators for detergent applications.
This gene encodes one of the smaller subunits of TFIID that binds to the basal transcription factor GTF2B as well as to several transcriptional activators such as p53 and VP16. A similar but distinct gene (TAF9B) has been found on the X chromosome and a pseudogene has been identified on chromosome 19. Alternative splicing results in multiple transcript variants encoding different isoforms.
Reporter genes can also be expressed by induction during growth. In these cases, trans-acting elements, such as transcription factors are used to express the reporter gene. Reporter gene assay have been increasingly used in high throughput screening (HTS) to identify small molecule inhibitors and activators of protein targets and pathways for drug discovery and chemical biology. Because the reporter enzymes themselves (e.g.
Hydrogen peroxide is insufficiently active as a bleach at temperature below 60°C, which traditionally made hot washes the norm. The development of bleach activators in the 1970s and 80s allowed for cooler washing temperatures to be effective. These compounds, such as tetraacetylethylenediamine (TAED), react with hydrogen peroxide to produce peracetic acid, which is an even more effective bleach, particularly at lower temperatures.
Dock2 ( _D_ edicator _o_ f _c_ yto _k_ inesis 2), also known as DOCK2, is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac.
However, cyclin A2/CDK complexes do not function strictly as activators of cyclin B1/CDK1 in G2, as CDK2 has been shown to be required for activation of the p53-independent G2 checkpoint activity, perhaps through a stabilizing phosphorylation on Cdc6. CDK2-/- cells also have aberrantly high levels of Cdc25A. Cyclin A2/CDK1 has also been shown to mediate proteasomal destruction of Cdc25B.
This family of transcription factors are exclusive to vascular plants. They can be divided into two groups, TCP-C and TCP-P, that appear to have separated following an early gene duplication event. This duplication event may have led to functional divergence and it has been proposed that the TCP-P subfamily are transcriptional repressors, while the TPC-C subfamily are transcription activators.
Particular promoters can be placed upstream of the luc gene, that is, the luc sequence can be fused to the promoter sequence at DNA level. If such construct is not too large in size, it can simply be introduced into eukaryotic cells using plasmids. This approach is widely used to study the activity of a given promoter in a given cell/tissue type, since the amount of light produced by the luciferase is directly proportional to the promoter activity. In addition to studying the promoters, firefly luciferase assays offer the option of studying transcriptional activators: in these experiments typically the GAL4/UAS_system is used and its Gal4 upstream activating DNA sequence (UAS) is placed upstream the luc gene while the different activators or the different variants/fragments of the same activator are fused to the GAL4 DNA binding module at protein level.
This update also enabled the ability to customize the motion-sensing controls to be used for virtual reality games. A second update in June 2016 enabled buttons to be "Activators" which can respond differently based on the type of input on the button, distinguishing between a single short tap, an extended hold, and a double-tap, for example. Activators can also be used to simulate the constant holding of a button with a single press, such as often used for the action of crouching in many first-person or third-person shooters. Valve is planning on supporting similar controller customization features and user interfaces to other compatible controllers, and released the first such update in the Steam software for Sony's DualShock 4 controller in December 2016, and beta support for other controllers including Xbox One in January 2017.
These modifications act in a context dependent manner to promote TBX3 protein stability, nuclear localization and transcriptional activity. TBX3 can activate and/or repress its target genes by binding a T-element, or half T-element sites. Indeed, Tbx3 binds highly conserved T-elements to activate the promoters of Eomes, T, Sox17 and Gata6, which are factors essential for mesoderm differentiation and extra embryonic endodermal. Furthermore, in the cancer context, TBX3 directly represses the cell cycle regulators p19ARF/p14ARF , p21WAF1 and TBX2 as well as E-cadherin which encodes a cell adhesion molecule, to promote proliferation and migration. TBX3 directly represses a region of the PTEN promoter which lacks putative T-elements, but which forms an important regulatory unit for PTEN transcriptional activators, thus raising the possibility that TBX3 may also repress some of its target genes through interfering with transcriptional activators.
Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present. CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.. CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.
The ACTIVATE program was created in order to empower youth to drive their own physical activity projects in their communities through Youth Driven Development (YDD). The ACTIVATE Program consists of leadership training opportunities including the ACTIVATE National Youth Leadership Conference and ACTIVATE Regional Forums. After participating, ACTIVATORS plan and implement their projects, which usually focus on community sports, with the support of Motivate Canada staff members.
This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme.
MAML proteins may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C), tumour suppressor pathway (p53) and colon carcinoma survival (beta-catenin). MAML proteins could mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.
The minimization of amino acid racemization during coupling is also of vital importance to avoid epimerization in the final peptide product. Amide bond formation between an amine and carboxylic acid is slow, and as such usually requires 'coupling reagents' or 'activators'. A wide range of coupling reagents exist, due in part to their varying effectivness for particular couplings, many of these reagents are commercially available.
Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene. It forms part of the Mediator complex. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus.
Ras GTPase-activating protein nGAP is an enzyme that in humans is encoded by the RASAL2 gene. This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system.
Peroxy acids are more active bleaches than hydrogen peroxide at lower temperatures (<60 °C) but are too unstable to be stored in their active form and hence must be generated in situ. The most common bleach activators used commercially are tetraacetylethylenediamine (TAED) and sodium nonanoyloxybenzenesulfonate (NOBS). NOBS is the main activator used in the U.S.A. and Japan, TAED is the main activator used in Europe.
Constructed from an elastomeric material, these preformed activators are used in the primary to adult dentition but ideal for use in the early through late mixed dentition. Along with their activator properties, ideal for correction of class II malocclusion, being based on tooth size, these appliances aptly coined EGAs (Eruptive Guidance Appliances) also function as a positioner along with correcting overbite and mild to moderate crowding.
Purified chymopapain is the main component of the injection, composed basically of 20 mg in five millilitres. It is provided in vials containing 10.000 units of the lyophilized agent with 0.37 mg of disodium edetate, 3.5 mg of cysteine hydrochloride monohydrate and 1.0 mg of bisulfide. All of them work as stabilisers and activators. Sodium hydroxide is in charge of adjusting the PH of the solution.
Depressants inhibit the flotation of one mineral or minerals while activators enable the flotation of others. Examples of these include CN−, used to depress all sulfides but galena and this depressant is believed to operate by changing the solubility of chemisorbed and physisorbed collectors on sulfides. This theory originates from Russia. An example of an activator is Cu2+ ions, used for the flotation of sphalerite.
TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators.
The use of a triple filament or multifilament set-up improves ionization efficiency and provides the rate of evaporation and ionization to be controlled separately. Filaments need to be loaded with activators. An activator represses the evaporation of the desired element and can either increase or decrease the ionization potential of the filament. This results in high ionization efficiency and a higher total yield.
Ostromislensky pioneered the studies of non-sulfur activators of vulcanization of rubber. He also proposed organic additions to rubber, such as toluidine and naphthylamine, in order to improve its properties. Those additives were later exploited by US companies, such as Union Carbide. In 1913, Ostromislensky published a book on "Rubber and its analogs", which was the first Russian textbook on chemistry and technology of rubber.
The entire list of functions of UCP2 and UCP3 is not known. However, studies indicate that these proteins are involved in a negative-feedback loop limiting the concentration of reactive oxygen species (ROS). Current scientific consensus states that UCP2 and UCP3 perform proton transportation only when activation species are present. Among these activators are fatty acids, ROS, and certain ROS byproducts that are also reactive.
Kraft et al. have shown that the substrates' D boxes bind directly to the highly conserved WD40 repeat propeller region on the APC activators. It is important to note that the conserved area of the propeller of Cdh1 is much larger than that of Cdc20, allowing Cdh1 to have a broader substrate specificity, consistent with the fact that APC/CCdh1 also activates APC-mediated destruction of KEN box containing substrates.
The cell fate can be effectively manipulated by epigenome editing. In particular, by directly activating of specific endogenous gene expression with CRISPR-mediated activator. When dCas9 (that has been modified so that it no longer cuts DNA, but still can be guided to specific sequences and to bind to them) is combined with transcription activators, it can precisely manipulate endogenous gene expression. Using this method, Wei et al.
Interferons induce the formation of two transcriptional activators: gamma- activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). A natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease was found in two unrelated patients with unexplained mycobacterial disease. Dupuis S, Dargemont C, Fieschi C, et al. Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science. 2001;293(5528):300–303.
A wide range of environmental organotins that mimic petidergic hormones in the HPA axis as mentioned before, additionally mimic lipid activators of the cannabinoid system and inhibit AMPK activity. Endocannaboid levels are high in those suffering from obesity due to hyperactivity of cannaboid signalling pathways. It is these high levels that have been found to be closely associated with increased fat stores linking the lipid activator mimics to the actual disease.
AF4/FMR2 family member 1 is a protein that in humans is encoded by the AFF1 gene. At its same location was a record for a separate PBM1 gene, which has since been withdrawn and considered an alias. It was previously known as AF4 (ALL1-fused gene from chromosome 4). The gene is a member of the AF4/FMR2 (AFF) family, a group of nuclear transcriptional activators which encourage RNA elongation.
HES1 also plays an important role in the Notch signaling pathway. In the absence of Notch signaling, RBPJ inhibits the expression of HES1. After Notch signals have been processed within the cell, however, the plasma membrane releases the intracellular domain of Notch, which moves to the nucleus where it associates with RBPJ. The binding causes a conformational change which leads co- repressors to disassociate and allows co-activators to bind.
Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RASGRP3, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000).
Most applications have been directed toward the detection of environmentally harmful chemicals, such as those affecting the endocrine system (environmental hormones). CALUX is an effect based screening method as it measures the total effect ligands (from a sample) have on a specific receptor. Unlike chemical analysis, CALUX is thus able to measure total activity on the receptor of interest. This includes both identified and unidentified activators (agonists) and inhibitors (receptor antagonists).
Regulator of G-protein signaling 5 is a protein that in humans is encoded by the RGS5 gene. The regulator of G protein signaling (RGS) proteins are signal transduction molecules that have structural homology to SST2 of Saccharomyces cerevisiae and EGL-10 of Caenorhabditis elegans. Multiple genes homologous to SST2 are present in higher eukaryotes. RGS proteins are involved in the regulation of heterotrimeric G proteins by acting as GTPase activators.
Msx2-interacting protein is a protein that in humans is encoded by the SPEN gene. This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins.
First, two lists are made that form two nonintersecting partitions: the list of objects and the list of rules. Objects are denoted by circles. Each rule in a mivar network is an extension of productions, hyper-rules with multi-activators or computational procedures. It is proved that from the perspective of further processing, these formalisms are identical and in fact are nodes of the bipartite graph, denoted by rectangles.
Antigonadotropins may also have the effect of lowering circulating neurosteroid levels. The translocator protein (TSPO), also initially described as the peripheral benzodiazepine receptor (PBR), is a mitochondrial protein that is involved in neurosteroid biosynthesis. It is activated by certain benzodiazepines such as diazepam and midazolam, and via this action, inhibitory neurosteroid levels are increased. Selective TSPO activators, such as emapunil, are under investigation for clinical use as possible anxiolytics.
Signal transducer and activator of transcription 6 (STAT6) is a human gene. The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein plays a central role in exerting IL4 mediated biological responses.
HATs are part of a multiprotein complex that is recruited to chromatin when activators bind to DNA binding sites. Acetylation effectively neutralizes the basic charge on lysine, which was involved in stabilizing chromatin through its affinity for negatively charged DNA. Acetylated histones therefore favor the dissociation of nucleosomes and thus unwinding of chromatin can occur. Under a loose chromatin state, DNA is more accessible to transcriptional machinery and thus expression is activated.
Activators are maximally expressed late in G1 and can be found in association with E2F regulated promoters during the G1/S transition. The activation of E2F-3a genes follows upon the growth factor stimulation and the subsequent phosphorylation of the E2F inhibitor retinoblastoma protein, pRB. The phosphorylation of pRB is initiated by cyclin D/cdk4, cdk6 complex and continued by cyclin E/cdk2. Cyclin D/cdk4,6 itself is activated by the MAPK signaling pathway.
Scientists have found that binding depressors to Bcl-2 anti-apoptotic proteins inhibits them and leaves direct activators free to interact with Bax and Bak. Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase activity blocks cell death in human disease including neurodegenerative disorders, stroke, heart attack and liver injury. Therefore, caspase inhibitors are a promising pharmacological tool providing treatments for stroke and other human diseases.
KMT2D is partially functionally redundant with KMT2C in the liver as well. Heterozygous Kmt2d+/- mice exhibit enhanced glucose tolerance and insulin sensitivity and increased serum bile acid. KMT2C and KMT2D are significant epigenetic regulators of the hepatic circadian clock and are co- activators of the circadian transcription factors retinoid-related orphan receptor (ROR)-α and -γ. In mice, KMT2D also acts as a coactivator of PPARγ within the liver to direct over-nutrition induced steatosis.
PAMPs are known to be potent activators of innate immune signaling. There are approximately 10 human Toll-Like Receptors (TLRs). Different TLRs in human detect different PAMPS: lipopolysaccharides by TLR4, viral dsRNA by TLR3, viral ssRNA by TLR7/TLR8, viral or bacterial unmethylated DNA by TLR9. TLR9 has evolved to detect CpG DNA commonly found in bacteria and viruses and to initiate the production of IFN (type I interferons ) and other cytokines.
The pathogenesis of NCGS is not yet well understood. For this reasons, it is a controversial syndrome and some authors still question it. There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system.
Furthermore, specific LTBP isoforms have a propensity to associate with specific TGF-β isoforms. For example, LTBP-4 is reported to bind only to TGF-β1, thus, mutation in LTBP-4 can lead to TGF-β associated complications which are specific to tissues that predominantly involves TGF-β1. Moreover, the structural differences within the LTBP’s provide different latent TGF-β complexes which are selective but to specific stimuli generated by specific activators.
Nevertheless, the p50 and p52 NF-κB members play critical roles in modulating the specificity of NF-κB function. Although homodimers of p50 and p52 are, in general, repressors of κB site transcription, both p50 and p52 participate in target gene transactivation by forming heterodimers with RelA, RelB, or c-Rel. In addition, p50 and p52 homodimers also bind to the nuclear protein Bcl-3, and such complexes can function as transcriptional activators.
However, acetylation is not always associated with enhanced transcriptional activity. For instance, acetylation of H4K12 has been associated with condensed and transcriptionally inactive chromatin. In addition, some histone modifications are associated with both enhanced and repressed activity, in a context-dependent manner. HATs act as transcriptional co-activators or gene silencers and are most often found in large complexes made up of 10 to 20 subunits, some of which shared among different HAT complexes.
Specific protein activators regulate the PIKK kinases but binding of them to the kinase complex causes a conformational change that increases substrate access to the kinase domain. Protein kinases have become popular drug targets. They have been targeted for the discovery and design of small molecule inhibitors and biologics as potential therapeutic agents. Small-molecule inhibitors of protein kinases generally prevent either phosphorylation of proteins substrates or autophosphorylation of the kinase itself.
All steps in the transcription are subject to some degree of regulation. Transcription initiation in particular is the primary level at which gene expression is regulated. Targeting the rate-limiting initial step is the most efficient in terms of energy costs for the cell. Transcription initiation is regulated by cis-acting elements (enhancers, silencers, isolators) within the regulatory regions of the DNA, and sequence-specific trans-acting factors that act as activators or repressors.
Next day sedation can be worsened if people take zolpidem while they are also taking antipsychotics, other sedatives, anxiolytics, antidepressant agents, antiepileptic drugs, and antihistamines. Some people taking antidepressants have had visual hallucinations when they also took zolpidem. Cytochrome P450 inhibitors, particularly CYP3A4 and CYP1A2 inhibitors, fluvoxamine and ciprofloxacin will increase the effects of a given dose of zolpidem. Cytochrome P450 activators like St. John's Wort may decrease the activity of zolpidem.
MetaCyc includes mini reviews for pathways and enzymes that provide background information as well as relevant literature references. It also provides extensive data on individual enzymes, describing their subunit structure, cofactors, activators and inhibitors, substrate specificity, and, when available, kinetic constants. MetaCyc data on metabolites includes chemical structures, predicted Standard energy of formation, and links to external databases. Reactions in MetaCyc are presented in a visual display that includes the structures of all components.
Efficiency of UCNPs doped with only activators is usually low, due to their low absorption cross section and necessarily low concentration. Sensitizer ions are doped into the host lattice along with the activator ions in UCNPs to facilitate Electron Transfer Upconversion. The most commonly used sensitizer ion is trivalent Yb3+. This ion provides a much larger absorption cross- section for incoming near-IR radiation, while only displaying a single excited 4f state.
C/EBPα bZip domain bound to DNA. PDB entry CCAAT-enhancer-binding proteins (or C/EBPs) is a family of transcription factors composed of six members, named from C/EBPα to C/EBPζ. They promote the expression of certain genes through interaction with their promoters. Once bound to DNA, C/EBPs can recruit so-called co-activators (such as CBP) that in turn can open up chromatin structure or recruit basal transcription factors.
However, the terms single- and multi-unit smooth muscle represents an oversimplification. This is due to the fact that smooth muscles for the most part are controlled and influenced by a combination of different neural elements. In addition, it has been observed that most of the time there will be some cell to cell communication and activators/ inhibitors produced locally. This leads to a somewhat coordinated response even in multiunit smooth muscle.
This balance is the proportion of proapoptotic homodimers that form in the outer-membrane of the mitochondrion. The proapoptotic homodimers are required to make the mitochondrial membrane permeable for the release of caspase activators such as cytochrome c and SMAC. Control of proapoptotic proteins under normal cell conditions of nonapoptotic cells is incompletely understood, but in general, Bax or Bak are activated by the activation of BH3-only proteins, part of the Bcl-2 family.
IFN-α8 enhances the proliferation of human B cells, as well as being able to activate NK cells. The subtypes α10 and α2, along with α8, are the most efficient and powerful NK cell activators. Subtypes α21 and α2 enhance the expression of IFN-gamma-inducible protein-10 (IP-10) in dendritic cells. Activated dendritic cells initiate immune responses and induce the expression of IP-10, a chemokine which promotes a Th1 inflammatory response.
Amongst members of the ETS family, there is extensive conservation in the DNA-binding ETS domain and, therefore, a lot of redundancy in DNA binding. It is thought that interactions with other proteins (eg: Modulator of the activity of Ets called Mae) is one way in which specific binding to DNA is achieved. Transcription factor Ets are a site of signalling convergence. ETS factors act as transcriptional repressors, transcriptional activators, or both.
The main inhibitor of tissue plasminogen activator and urokinase is plasminogen activator inhibitor-1 (PAI-1). Plasminogen activator inhibitor-1 is a serine protease, synthesized by endothelial cells, that specifically inhibits tissue plasminogen activator (tPA) and urokinase (uPA). Tissue plasminogen activator and urokinase are the activators of plasminogen and results in the breakdown of blood clots (fibrinolysis). PAI-1 levels has also been studied in patients and how they influence certain diseases.
DNA binding protein ERG fuses with RNA binding proteins EWS and TLS/FUS in Ewing's sarcoma and acute myeloid leukemias respectively and function as transcriptional activators. ERG and its fusion proteins EWS-ERG and TLS/FUS-ERG inhibit apoptosis. Morpholino splice- switching oligonucleotides have been used to induce exon 4 skipping in prostate cancer cell lines, mouse models and tissue explants, leading to anti- cancer effects, including reduction of proliferation and induction of apoptosis.
PAK4 activity is stimulated by upstream activators and signals, including by HGF, PKD, PKA, CDK5RAP3, and SH3RF2. In addition to other mechanisms, PAK4 functions are mediated though phosphorylation of its effector proteins, including, LIMK1-Thr508, integrin β5-Ser759/Ser762, p120-catenin-Ser288, superior cervical ganglia 10 (SCG10)-Ser50, GEF-H1-Ser810 β-catenin-Ser675, and Smad2-Ser465. PAK4 and/or PAK4-dependent signals also modulate the expression of genomic targets, including MT1-MMP and p57Kip2.
When the Hippo pathway is not activated, YAP1/TAZ enter the nucleus and regulate gene expression. It is reported that several genes are regulated by YAP1, including Birc2, Birc5, connective tissue growth factor (CTGF), amphiregulin (AREG), Cyr61, Hoxa1 and Hoxc13. YAP/TAZ have also been shown to act as stiffness sensors, regulating mechanotransduction independently of the Hippo signalling cascade. As YAP and TAZ are transcriptional co-activators, they do not have DNA-binding domains.
Many EAEC encode a transcriptional factor named aggR (aggregative regulator), part of the AraC family of transcription activators. AggR regulates many plasmid, as well chromosomally encoded, virulence factors, that include genes implicated in aggregative adherence fimbriae biogenesis and toxin production. Several toxins have been linked to EAEC virulence, including ShET1 (Shigella enterotoxin 1), Pet (plasmid‐encoded toxin), and EAST-1. However, further studies of these factors have failed to elucidate their role in pathogenesis.
They are also used in pesticides. Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity, while enzyme substrates bind and are converted to products in the normal catalytic cycle of the enzyme. The binding of an inhibitor can stop a substrate from entering the enzyme's active site and/or hinder the enzyme from catalyzing its reaction. Inhibitor binding is either reversible or irreversible.
With respect to PFK1, fructose 2,6-bisphosphate and ADP are examples of metabolites that are allosteric activators. Physiological enzyme inhibition can also be produced by specific protein inhibitors. This mechanism occurs in the pancreas, which synthesises many digestive precursor enzymes known as zymogens. Many of these are activated by the trypsin protease, so it is important to inhibit the activity of trypsin in the pancreas to prevent the organ from digesting itself.
Cyclohexylthiophthalimide is used to impede the onset of vulcanization. To ensure high quality vulcanization, the rubber, sulfur, accelerants, activators and other compounds are blended to give a homogeneous mixture. In practice, mixing can result in melting the sulfur (melting point 115 °C for S8). At these temperatures vulcanization can begin prematurely, which is often undesirable, as the mixture may still need to be pumped and moulded into its final form before it sets solid.
While viral latency exhibits no active viral shedding nor causes any pathologies or symptoms, the virus is still able to reactivate via external activators (i.e. sunlight, stress) to cause an acute infection. In the case of herpes simplex virus, which generally infects an individual for life, a serotype of the virus reactivates occasionally to cause cold sores. Although the sores are quickly resolved by the immune system, they may be a minor annoyance from time to time.
Fluorescence of Aragonite Gemstones, minerals, may have a distinctive fluorescence or may fluoresce differently under short-wave ultraviolet, long-wave ultraviolet, visible light, or X-rays. Many types of calcite and amber will fluoresce under shortwave UV, longwave UV and visible light. Rubies, emeralds, and diamonds exhibit red fluorescence under long-wave UV, blue and sometimes green light; diamonds also emit light under X-ray radiation. Fluorescence in minerals is caused by a wide range of activators.
Trivalent chromium at low concentration is the source of the red fluorescence of ruby. Divalent europium is the source of the blue fluorescence, when seen in the mineral fluorite. Trivalent lanthanides such as terbium and dysprosium are the principal activators of the creamy yellow fluorescence exhibited by the yttrofluorite variety of the mineral fluorite, and contribute to the orange fluorescence of zircon. Powellite (calcium molybdate) and scheelite (calcium tungstate) fluoresce intrinsically in yellow and blue, respectively.
Dock3 ( _D_ edicator _o_ f _c_ yto _k_ inesis 3), also known as MOCA ( _m_ odifier _o_ f _c_ ell _a_ dhesion) and PBP ( _p_ resenilin- _b_ inding _p_ rotein), is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock3 specifically activates the small G protein Rac.
In addition to the three C-terminal WH2 domains, also the presence of the linker region L2 between the second and third WH2 domain was of importance for Cobl-mediated actin nucleation. Cobl assembles non-bundled, unbranched actin filaments. In contrast to other actin nucleators, which are directly or indirectly via their activators controlled by Rho type GTPases, Cobl hereby is controlled by calcium/calmodulin signalling and by arginine methylation brought about by the arginine methyltransferase 2 PRMT2.
However, when it bonds to the second subunit of myosin phosphatase, MYPT1 (MW ~130 kDa), this catalytic cleft changes configuration. This results in a dramatic increase in myosin specificity. Thus, it is clear that MYPT1 has great regulatory power over PP1 and myosin phosphatase, even without the presence of other activators or inhibitors. The third subunit, M20 (not to be confused with MLC20, the critical regulatory subunit of myosin), is the smallest and most mysterious subunit.
Many different types of proteins can affect the level of gene expression by promoting or preventing transcription. In prokaryotes (such as bacteria), these proteins often act on a portion of DNA known as the operator at the beginning of the gene. The promoter is where RNA polymerase, the enzyme that copies the genetic sequence and synthesizes the mRNA, attaches to the DNA strand. Some genes are modulated by activators, which have the opposite effect on gene expression as repressors.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g.
Suggested by the idea that the structure of chromatin can be modified to allow or deny access of transcription activators, regulatory functions of histone acetylation and deacetylation can have implications with genes that cause other diseases. Studies on histone modifications may reveal many novel therapeutic targets. Based on different cardiac hypertrophy models, it has been demonstrated that cardiac stress can result in gene expression changes and alter cardiac function. These changes are mediated through HATs/HDACs posttranslational modification signaling.
When a comet passed by Earth, it activated a genetic quirk in some people that would manifest into superpowers either naturally or through special Seedlings called Activators. Swift was one such Seedling. Swift was brought into Stormwatch as a rookie, with her powers only partially activated. Weatherman Henry Bendix later reconfigured the Stormwatch teams, assigning her to Stormwatch Black, Stormwatch's black ops team, alongside Jenny Sparks (with whom she had a brief romance) and Jack Hawksmoor.
TFIIA interacts with the TBP subunit of TFIID and aids in the binding of TBP to TATA-box containing promoter DNA. Interaction of TFIIA with TBP facilitates formation of and stabilizes the preinitiation complex. Interaction of TFIIA with TBP also results in the exclusion of negative (repressive) factors that might otherwise bind to TBP and interfere with PIC formation. TFIIA also acts as a coactivator for some transcriptional activators, assisting with their ability to increase, or activate, transcription.
As opposed to barbital, BZDs are not GABA-receptor activators and rely on increasing the neurotransmitter's natural activity. Bromazepam is an intermediate-acting benzodiazepine, is moderately lipophilic compared to other substances of its class and metabolised hepatically via oxidative pathways. It does not possess any antidepressant or antipsychotic qualities. After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.
In specific cell types or on specific promoters TBP can be replaced by one of several TBP-related factors (TRF1 in Drosophila, TBPL1/TRF2 in metazoans, TBPL2/TRF3 in vertebrates), some of which interact with the TATA box similar to TBP. Interaction of TATA boxes with a variety of activators or repressors can influence the transcription of genes in many ways. Enhancers are long-range regulatory elements that increase promoter activity while silencers repress promoter activity.
HATs are traditionally divided into two different classes based on their subcellular localization. Type A HATs are located in the nucleus and are involved in the regulation of gene expression through acetylation of nucleosomal histones in the context of chromatin. They contain a bromodomain, which helps them recognize and bind to acetylated lysine residues on histone substrates. Gcn5, p300/CBP, and TAFII250 are some examples of type A HATs that cooperate with activators to enhance transcription.
L. monocytogenes can act as a saprophyte or a pathogen, depending on its environment. When this bacterium is present within a host organism, quorum sensing and other signals cause the up-regulation of several virulence genes. Depending on the location of the bacterium within the host organism, different activators up-regulate the virulence genes. SigB, an alternative sigma factor, up-regulates Vir genes in the intestines, whereas PrfA up-regulates gene expression when the bacterium is present in blood.
Antifibrinolytics are a class of medication that are inhibitors of fibrinolysis. Examples include aminocaproic acid (ε-aminocaproic acid) and tranexamic acid. These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin. These drugs block the binding sites of the enzymes or plasminogen respectively and thus stop plasmin formation.
Recruitment of other transcription co-factors (including co- activators and co-repressors) and general transcriptional machinery further ensures the transactivation of AR-regulated gene expression. All these complicated processes are initiated by the ligand-induced conformational changes in the LBD. Ligand specific recruitment of coregulators might be crucial for the agonist or antagonist activity of AR ligands. Binding of DNA is also required for AR-regulated gene expression, also known as classic genomic gene function of AR.
Because of its single-ion nature, ESA does not depend on the lanthanide ion concentration. Two-ion processes are usually dominated by energy transfer upconversion (ETU). This is characterized by the successive transfer of energy from singly excited ions (sensitizers/donors), to the ion which eventually emits (activators/acceptors). This process is commonly portrayed as the optical excitation of the activator followed by further excitation to the final fluorescing state due to energy transfer from a sensitizer.
An extreme example is orotidine 5'-phosphate decarboxylase, which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: inhibitors are molecules that decrease enzyme activity, and activators are molecules that increase activity.
The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage. Some coactivators also have histone acetyltransferase (HAT) activity.
HATs form large multiprotein complexes that weaken the association of histones to DNA by acetylating the N-terminal histone tail. This provides more space for the transcription machinery to bind to the promoter, therefore increasing gene expression. Activators are found in all living organisms, but coactivator proteins are typically only found in eukaryotes because they are more complex and require a more intricate mechanism for gene regulation. In eukaryotes, coactivators are usually proteins that are localized in the nucleus.
Enhancers and silencers may be distantly located from the gene, many thousands of base pairs away. The binding of different transcription factors, therefore, regulates the rate of transcription initiation at different times and in different cells. Regulatory elements can overlap one another, with a section of DNA able to interact with many competing activators and repressors as well as RNA polymerase. For example, some repressor proteins can bind to the core promoter to prevent polymerase binding.
Growth factors that indirectly affect angiogenesis are also targets of proteolytic activation. For example, plasminogen activators drive the activation of latent transforming growth factor beta (TGF-β) from bone ECM and thus modulate angiogenesis in bone. Proteases not only have the ability change the availability of growth factors, but can also modify their properties. This ability was shown for VEGF165 that is cleaved by MMP-3 or MMP-9 to a smaller molecule with properties similar to VEGF121.
The proteolytic activities that take place during angiogenesis require precise spatial and temporal regulation. If not for this control excessive proteolysis could lead to damage of the tissue and the loss of anchorage points for migrating cells. This is illustrated by mice which are deficient for plasminogen activator inhibitor-1 (PAI-1). PAI-1 inhibits plasminogen activators and thus plasmin activation; therefore it could be assumed that PAI-1 deficiency would increase angiogenesis and tumor growth.
One of the most interesting developments in biomedical science during the past few decades has been elucidation of mechanisms mediating innate immunity. One set of innate immune mechanisms is humoral, such as complement activation. Another set comprises pattern recognition receptors such as toll-like receptors, which induce the production of interferons and other cytokines increasing resistance of cells such as monocytes to infections. Cytokines produced during innate immune responses are among the activators of adaptive immune responses.
RanGAP1, is a homodimeric 65-kD polypeptide that specifically induces the GTPase activity of RAN, but not of RAS by over 1,000-fold. RanGAP1 is the immediate antagonist of RCC1, a regulator molecule that keeps RAN in the active, GTP-bound state. The RANGAP1 gene encodes a 587-amino acid polypeptide. The sequence is unrelated to that of GTPase activators for other RAS-related proteins, but is 88% identical to Rangap1 (Fug1), the murine homolog of yeast Rna1p.
This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene.
250px Seen here is a four step diagram depicting the usage of an enhancer. Within this DNA sequence, protein(s) known as transcription factor(s) bind to the enhancer and increase the activity of the promoter. In genetics, an enhancer is a short (50–1500 bp) region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcription factors.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co- activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g.
The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related to ADP-ribosylation factors (ARFs). ARFs, described as activators of cholera toxin (CT) ADP-ribosyltransferase activity, regulate intracellular vesicular membrane trafficking, and stimulate a phospholipase D (PLD) isoform. Although, ARL proteins were initially thought not to activate CT or PLD, later work showed that they are weak stimulators of PLD and CT in a phospholipid dependent manner.
During transport, translation of oskar is repressed by the RNA-binding protein Bruno, which is in turn released by the binding of activators (e.g. Orb) upon arrival at the posterior pole. After proper localization, oskar RNA is translated and organizes germ plasm by recruiting other proteins such as Vasa. Her lab's current research continues to focus on spatial and temporal control of translation and which role ribonucleoprotein complexes (RNPs), cytoskeletal polarization and cytoskeletal motors play in RNA localization.
KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are in vitro activators of KLK7. Once active, KLK7 is able to cleave desmocollin and corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum.
There are a number of activation devices used for snow melting applications. Some activators are a simple manual timer that activate the system to stay on for a specified time period while others sense temperature and moisture or just temperature conditions to automatically activate the snow melt system. Automatic devices can be aerial-mounted, pavement mounted or gutter mounted. High-end activation devices feature adjustable temperature trigger points, adjustable delay off cycle, and upgradeable remote activation.
Maximum Time Aloft boomerangs mostly have one wing considerably longer than the other. This feature, along with carefully executed bends and twists in the wings help to set up an "auto-rotation" effect to maximise the boomerang's hover time in descending from the highest point in its flight. Some boomerangs have turbulators — bumps or pits on the top surface that act to increase the lift as boundary layer transition activators (to keep attached turbulent flow instead of laminar separation).
Although the original Stieglitz reaction is best known for the rearrangement of trityl hydroxylamines, there are several variations which include good leaving groups as N-substituents (such as halogens and sulfonates). Different reagents are commonly applied, depending on the exact nature of the substrate. They function as electrophilic activators for the hydroxyl group by increasing the quality of the leaving group. For example, when using PCl5 as a reagent, the trityl hydroxylamine is first transformed into the activated intermediate via a nucleophilic substitution.
Two years later, he moved to Memorial Sloan Kettering Cancer Center as chair of the cell biology program. In 2005, there was an abundance of activators and targets of the Rho pathway that had been identified, yet very little investigation into the way in which specificity of the pathway is maintained. It was known at this point that several identified Rho targets were structurally similar to scaffold proteins, which have been shown in the past to mediate interaction specificity in other pathways.
Ash1 was discovered as a gene causing an imaginal disc mutant phenotype in Drosophila. Ash1 is a member of the trithorax-group (trxG) of proteins, a group of transcriptional activators that are involved in regulating Hox gene expression and body segment identity. Drosophila Ash1 interacts with trithorax to regulate ultrabithorax expression. The human ASH1L gene spans 227.5 kb on chromosome 1, band q22. This region is rearranged in a variety of human cancers such as leukemia, non-Hodgkin’s lymphoma, and some solid tumors.
This gene encodes a protein that may regulate endothelial cell differentiation. It has been postulated that the protein functions as a bridging molecule that interconnects regulatory proteins and the basal transcriptional machinery, thereby modulating the transcription of genes involved in endothelial differentiation. This protein has also been found to act as a transcriptional coactivator by interconnecting the general transcription factor TATA element-binding protein (TBP) and gene- specific activators. Two alternatively spliced transcripts which encode distinct proteins have been found for this gene.
This hypothesis is supported by the existence of a number of small molecule agonists and antagonists of the pathway that act on SMO. The binding of SHH relieves SMO inhibition, leading to activation of the GLI transcription factors (Process "5"): the activators Gli1 and Gli2 and the repressor Gli3. The sequence of molecular events that connect SMO to GLIs is poorly understood. Activated GLI accumulates in the nucleus (Process "6") and controls the transcription of hedgehog target genes (Process "7").
Locations can be used in two ways: either as a homebase or as a battlesite. When used as a homebase, one's team must match the team description, and the inherent ability applies to the game. Battlesites are somewhat different; they are an alternative to the ability to use 'any hero/character' specials. Instead of those specials, the deck may include character cards, called activators that appear on the list in the battlesite, and the battlesite itself may store specials those characters can play.
An activator binds to a site on the DNA molecule and causes an increase in transcription of a nearby gene. In prokaryotes, a well-known activator protein is the catabolite activator protein (CAP), involved in positive control of the lac operon. In the regulation of gene expression, studied in evolutionary developmental biology (evo-devo), both activators and repressors play important roles. Regulatory genes can also be described as positive or negative regulators, based on the environmental conditions that surround the cell.
In Drosophila, per mRNA levels oscillate with a period of approximately 24 hours, peaking during the early subjective night. The per product PER also oscillates with a nearly 24-hour period, peaking about six hours after per mRNA levels during the middle subjective night. When PER levels increase, the inhibition of per transcription increases, lowering the protein levels. However, because PER protein cannot directly bind to DNA, it does not directly influence its own transcription; alternatively, it inhibits its own activators.
The upstream activation sequence is found adjacently upstream to a minimal promoter (TATA box) and serves as a binding site for transactivators. If the transcriptional transactivator does not bind to the UAS in the proper orientation then transcription cannot begin. To further understand the function of an upstream activation sequence, it is beneficial to see its role in the cascade of events that lead to transcription activation. The pathway begins when activators bind to their target at the UAS recruiting a mediator.
Second, MAPK primes Smad4 for GSK3-mediated phosphorylations that cause transcriptional inhibition and also generate a phosphodegron used as a docking site by the ubiquitin E3 ligase Beta-transducin Repeat Containing (beta-TrCP) that polyubiquitinates Smad4 and targets it for degradation in the proteasome. Smad4 GSK3 phosphorylations have been proposed to regulate the protein stability during pancreatic and colon cancer progression. In the nucleus the heteromeric complex binds promoters and interact with transcriptional activators. SMAD3/SMAD4 complexes can directly bind the SBE.
The process is facilitated by a number of factors including architectural proteins (primarily CTCF and Cohesin), transcription factors, co-activators, and ncRNAs. Importantly, DNA looping can be used to regulate gene expression – looping events can repress or activate genes, depending on the elements involved. Approximately 50% of human genes are believed to be involved in long range chromatin interactions through the process of DNA looping. Looping was first observed by Walther Flemming in 1878 when he was studying amphibian oocytes.
KLF4 can activate transcription by interacting via it N-terminus with specific transcriptional co-activators, such as p300-CBP coactivator family. Transcriptional repression by KLF4 is carried out by KLF4 competing with an activator for binding to a target DNA sequence (9-12). KLF4 has been shown to interact with CREB-binding protein. It was found that the transcription factor Klf4 present at the promoter of an enzymatic subunit of telomerase (TERT), where it formed a complex with β-catenin.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [e.g.
STATs (signal transduction and activators of transcription) are members of a family of transcription factors, and they have src homology 2 (SH2) domains that allow them to bind to these phosphorylated tyrosine residues. After undergoing JAK-mediated phosphorylation, the STAT transcription factors dimerize, translocate to the nucleus, bind DNA at specific elements and induce expression of specific genes. Cytokine receptors selectively activate particular JAK-STAT pathways to induce transcription of different genes. IL-2 and IL-4 activate JAK1, JAK3 and STAT5.
Chemence (Inc., Ltd., Medical, Graphics) is a multinational conglomerate which manufactures products including cyanoacrylate adhesives, anaerobic adhesives, impregnation sealants, adhesive activators, epoxy resins, UV adhesives, photopolymer resins, custom printer ink cartridges, Gas pipe sealants, and soak off nail polishes. Chemence is a supplier of photopolymer and commercial printers to the flexographic industry in the US and Europe, as well as the primary sealant supplier to British Gas, and a primary supplier of private- label adhesives to companies including Tesco, 3M, Bostik, and Bondo.
While all the constructs showed significant direct activation, it decreased with increasing lncRNA-sgRNA length. These lncRNA domains could regulate the reporters independent of dCas9 with pRNA and RepA repressing the GLuc reporter expression (repressors) and TRERNA1, ncRNA-a3 and HOTTIP inducing activation (activators), but were properly targeted to an ectopic location of interest by using the CRISP-Disp system. Thus, CRISP-Disp enables control of gene expression with deployment of both artificial scaffolds as well as natural lncRNA domains.
The placement of a repressive mark on lysine 27 requires the recruitment of chromatin regulators by transcription factors. These modifiers are either histone modification complexes which covalently modify the histones to move around the nucleosomes and open the chromatin, or chromatin remodelling complexes which involve movement of the nucleosomes without directly modifying them. These histone marks can serve as docking sites of other co-activators as seen with H3K27me3. This occurs through polycomb mediated gene silencing via histone methylation and chromodomain interactions.
SV40 large T antigen (Simian Vacuolating Virus 40 TAg) is a hexamer protein that is a dominant-acting oncoprotein derived from the polyomavirus SV40. TAg is capable of inducing malignant transformation of a variety of cell types. The transforming activity of TAg is due in large part to its perturbation of the retinoblastoma (pRb) and p53 tumor suppressor proteins. In addition, TAg binds to several other cellular factors, including the transcriptional co- activators p300 and CBP, which may contribute to its transformation function.
Caspase-1, conserved in vertebrates, is involved in the canonical pathway and is activated by canonical inflammasomes such as NLRP3 and NLRC4 inflammasomes, which are multi-protein complexes that are formed upon recognition of specific inflammatory ligands called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the cytosol by NOD-like receptors (NLRs). Examples include bacterial type 3 secretion system (T3SS) rod protein and flagellin, which are potent activators of NLRC4 inflammasome, and bacterial toxin nigericin that activates NLRP3 inflammasome.
They were first discovered in 1993 and have been found to have structures analogous to replication factories, sites where replication also occurs in discrete sites. The factories contain an RNA polymerase (active or inactive) and the necessary transcription factors (activators and repressors) for transcription. Transcription factories containing RNA polymerase II are the most studied but factories can exist for RNA polymerase I and III; the nucleolus being seen as the prototype for transcription factories. It is possible to view them under both light and electron microscopy.
In general the up regulation of anti-apoptotic proteins leads to the prevention of apoptosis which can be solved by inhibitors and the down regulation of anti-apoptotic proteins leads to the induction of apoptosis which is reversed by activators that are able to bind and modify their activity. An important target molecule in apoptosis based therapies is Bcl-2 for drug design. Bcl-2 was the first oncogene found to cause cancer-inhibiting apoptosis. It is over expressed in tumors and is resistant to chemotherapy.
Furthermore, an absence of ZNF238 results in upregulation of the epithelial- mesenchymal transition process. In tumors such as medulloblastomas, the loss of ZNF238 can disorganize the tumor's cellular divisional processes, resulting in a cellularly diverse neoplasm. This new diversity has been observed to increase the invasiveness of the tumor, yielding proliferation into more areas of the brain than before the loss of ZNF238. C2H2-type zinc finger proteins, such as ZNF238, act on the molecular level as transcriptional activators or repressors and are involved in chromatin assembly.
The N-terminal end allows for the binding of various coactivators, corepressors, and modifiers. All family members share the zinc finger signature KLF-DBD of `CxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxCxxxxxxxxxxxxHxxxH` and use a 9aaTAD. KLFs are divided into three subgroups; Group 1 (KLF 3,8, and 12) are repressors via interaction with the C-terminal Binding Protein 1 and 2 (CtBP1 and CtBP2). Group 2 (KLFs 1,2,4,5,6, and 7) are transcription activators. Group 3 (KLFs 9,10,11,13,12, and 16) have repressor activity via interaction with the common transcriptional co-repressor, Sin3A.
The pathogenesis of NCGS is not yet well understood. There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system. FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in persons with NCGS.
Cdc20 and Cdh1, which are the activators of APC, recruit substrates such as securin and B-type cyclins(Clb) for ubiquitination. Without Cdk1-Clb2 complexes to phosphorylate proteins that are involved in spindle dynamics such as Sli15, Ase1, and Ask1, spindle elongation and chromosomal segregation are promoted, facilitating mitotic exit. The importance of proteolytic degradation in eukaryotic cell cycle changed the view of cell division as a simple kinase cascade to a more complex process in which interactions among phosphorylation, ubiquitination, and proteolysis are necessary.
Mediator of RNA polymerase II transcription subunit 7 is an enzyme that in humans is encoded by the MED7 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.
The network, according to the National Journal, supplies much of the potassium chlorate used in bombs employed by the Taliban in Afghanistan. Also, the network's bombs use more sophisticated remote triggering devices than the pressure-plated activators used elsewhere in Afghanistan. Sirajuddin Haqqani told MSNBC in April 2009 that his fighters had, "acquired the modern technology that we were lacking, and we have mastered new and innovative methods of making bombs and explosives."Dreazen, Yochi J., "The New Enemy", National Journal, 16 July 2011.
The company went public in September 2013. In 2004, he co-founded Sirtris Pharmaceuticals as CEO with Harvard biologist David Sinclair, serial entrepreneur Andrew Perlman, Richard Aldrich, Richard Pops, and Paul Schimmel. The company focused on resveratrol formulations and derivatives as activators of the SIRT1 enzyme. The company's initial product was called SRT501, and was a formulation of reservatrol. Westphal and Sinclair aggressively marketed investment in the company as an anti-aging opportunity, which was controversial but effective; Westphal raised $100 million in 2006.
Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.
The TnsC protein interacts with the transposase enzyme and the target DNA to promote the excision and insertion processes. The ability of TnsC to activate the transposase depends on its interaction with a target DNA along with its appropriate targeting protein, TnsD or TnsE. The TnsD and TnsE proteins are alternative target selectors that are also DNA binding activators that promote excision and insertion of Tn7. Their ability to interact with a particular target DNA is key to the target-site selection of Tn7.
Carpenter carried out research for her Ph.D. in the laboratory of Andrew S. Belmont at the University of Illinois, Urbana- Champaign. There, she developed molecular biology and automated imaging systems to rapidly assess the effects of transcriptional activators on large- scale chromatin structure using fluorescence microscopy. This work laid the foundation for studies of engineered regions of the genome, the movement of genes within the nucleus upon gene activation, and chromatin-related high- throughput screens. She received her PhD in cell biology in May 2003.
Ever since the birth of ICZ research in the late seventies, the field has been burgeoning with continued advances in both technology and organic chemistry techniques. While only a handful of ICZ based compounds have made it past stage II clinical trials, the sheer variety that these molecules can take on leaves much still unexplored territory. Of particular recent interest in synthesis techniques is the use of palladium based catalysts, which have been found to be excellent activators for use in formation of carbon-carbon bonds.
Upon binding to its cis-element, an activator can recruit polymerase directly or recruit other factors needed by the transcriptional machinery. An activator can also recruit nucleosome modifiers that alter chromatin in the vicinity of the promoter and thereby help initiation. Multiple activators can work together, either by recruiting a common or two mutually dependent components of the transcriptional machinery, or by helping each other bind to their DNA sites. These interactions can synergize multiple signaling inputs and produce intricate transcriptional responses to address cellular needs.
Furthermore, BK channels play a role in modulating the activity of dendrites as well as astrocytes and microglia. They not only play a role in the CNS (central nervous system) but also in smooth muscle contractions, the secretion of endocrine cells, and the proliferation of cells. Various γ subunits during early brain development are involved in neuronal excitability and in non-excitable cells they often are responsible as a driving force of calcium. Therefore, these subunits can be targets for therapeutic treatments as BK channel activators.
By contrast, type II activators such as VP16, p53 and E2F1, which supported both initiation and elongation, were able to bind to TFIIH. In one of the most thoroughly characterized transcription systems,Spilianakis C , Kretsovali A , Agalioti T , Makatounakis T , Thanos D , Papamatheakis J (2003) CIITA regulates transcription onset via Ser5-phosphorylation of RNA Pol II. EMBO J 22: 5125–5136 have studied the temporal order of recruitment of transcription factors during the activation of the major histocompatibility class II (MHC II) DRA gene by IFN-gamma.
UV radiation is found to be a possible cause of development of the autoimmune disease dermatomyositis, exposure to pesticides plays a role in rheumatoid arthritis development, and vitamin D has been found to be a key in preventing immune dysfunctions in older populations. Infectious agents are considered T cell activators, a step needed for activation of autoimmune diseases. These mechanisms are relatively unknown, but are one of the current theories to explain autoimmune diseases triggered by infection such as Guillain-Barre syndrome and rheumatic fever.
Interleukin 3 (IL3) is a cytokine that regulates hematopoiesis by controlling the production, differentiation and function of granulocytes and macrophages. The protein, which exists in vivo as a monomer, is produced in activated T cells and mast cells, and is activated by the cleavage of an N-terminal signal sequence. IL3 is produced by T lymphocytes and T-cell lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3 is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B.
Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.
DLC1 is known to be upregulated by at least two hormones: progesterone and peroxisome proliferators. In ovarian cancers, DLC-1 expression is upregulated by the steroid hormone progesterone. Gene profiling studies have shown that the addition of progesterone to ovarian cancer cell lines results in an increase in the expression of DLC1, which in turn results in growth inhibition, decreased cell motility, and increased caspase-3-mediated apoptosis. Lung cancer cells also increase DLC1 expression in response to peroxisome proliferator-activated receptor γ (PPARγ) activators.
The versatility of sgRNAs allows dCas9 activators to increase the expression of any gene within an organism's genome. That could be used to increase expression of a protein coding gene or a transcribed RNA. A paper demonstrated that genome wide activation could be used to determine which proteins are involved in mediated resistance to a specific drug. Another paper used genome wide activation of long, noncoding RNAs and observed that increasing the expression of certain long noncoding RNAs conferred resistance to the drug vemurafenib.
The NR5A1 gene encodes a 461-amino acid protein that shares several conserved domains consistent with members of the nuclear receptor subfamily. The N-terminal domain includes two zinc fingers and is responsible for DNA binding via specific recognition of target sequences. Variations of AGGTCA DNA motifs allows SF-1 to interact with the major groove of the DNA helix and monomerically bind. Following binding, trans-activation of target genes depends on recruitment of co-activators such as SRC-1, GRIP1, PNRC, or GCN5.
Small molecule allosteric activators of PDPK1 were shown to selectively inhibit activation of substrates that require docking site interaction. These compounds do not bind to the active site and allow PDPK1 to activate other substrates that do not require docking site interaction. PDPK1 is constitutively active and at present, there is no known inhibitor proteins for PDPK1. The activation of PDPK1's main effector, AKT, is believed to require a proper orientation of the kinase and PH domains of PDPK1 and AKT at the membrane.
Nitric oxide – activated macrophages produce large amounts of nitric oxide (NO), which induces both cytostasis and cytotoxicity to tumor cells both in vitro and in vivo. Nitric oxide-induced cytostasis targets ribonucleotide reductase by rapid and reversible inhibition. However, other studies show there could be other targets that are responsible for producing long-lasting cytostasis in cells. Lipopolysaccharide (LPS) and lipid A-associated protein – studies have demonstrated that LPS and LAP are potent macrophage activators that have been shown to stimulate tumoricidal (cytostatic) activity in vitro.
The activation device enables the snowmelt system to run 100% automated. Self-regulating trace heating cables automatically regulate the amount of heat supplied so that only those parts with temperatures below the set point are heated. Careful placement of the sensors is important to have an effective result when using these activators. Activation moisture sensors should be placed in a location where they will effectively collect any moisture from a snow storm and in relatively close proximity to the area to be free of snow and ice.
The data stored in SABIO-RK in a comprehensive manner is mainly extracted manually from literature. This includes reactions, their participants (substrates, products), modifiers (inhibitors, activators, cofactors), catalyst details (e.g. EC enzyme classification, protein complex composition, wild type / mutant information), kinetic parameters together with corresponding rate equation, biological sources (organism, tissue, cellular location), environmental conditions (pH, temperature, buffer) and reference details. Data are adapted, normalized and annotated to controlled vocabularies, ontologies and external data sources including KEGG, UniProt, ChEBI, PubChem, NCBI, Reactome, BRENDA, MetaCyc, BioModels, and PubMed.
The SIRT1 enzyme has HDAC activity, and has been shown to modulate energy metabolism and inflammation. SIRT1 overexpression or activation by resveratrol could improve insulin resistance and SIRT1 activators are being developed for diabetes treatment. The role of other HDACs and the potential use of HDAC inhibitors in diabetes is not very clear. Other treatments look towards an anti-inflammatory agent and HAT inhibitor, curcumin, which in trials ameliorated high glucose-induced inflammatory gene expression and histone acetylation at their promoters as well as changes in HAT and HDAC activities in human monocytes.
Other research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade microalgae that are effective activators of human monocytes/macrophages, including "Immunon" from Aphanizomenon flos-aquae. Immunostimulatory activity was measured using transcription factor-based bioassay. Each polysaccharide studied in this research, including AFA, substantially increased mRNA levels of interleukin and tumor necrosis factor-a (TNF-a). These polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.
Rap guanine nucleotide exchange factor 5 is a protein that in humans is encoded by the RAPGEF5 gene. Members of the RAS subfamily (see HRAS; MIM 190020) of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000).
Hypothesis about RELA acetylation suggests acetylation aids its subsequent recognition by transcriptional co- activators with bromodomains, which are specialized in recognizing acetylated lysine residues. Lysine 122 and 123 acetylation are found to be negatively correlated with RELA transcriptional activation. Unknown mechanisms mediate the acetylation of RELA possibly using p300/CBP and p300/CBP factor associated coactivators under TNFα or phorbol myristate acetate (PMF) stimulation both in vivo and in vitro. RELA is also under the control of deacetylation via HDAC, and HDAC3 is the mediator of this process both in vivo and in vitro.
RORα, RORβ, and RORγ are all transcriptional activators recognizing ROR- response elements. ROR-alpha is expressed in a variety of cell types and is involved in regulating several aspects of development, inflammatory responses, and lymphocyte development. The RORα isoforms (RORα1 through RORα3) arise via alternative RNA processing, with RORα2 and RORα3 sharing an amino-terminal region different from RORα1. In contrast to RORα, RORβ is expressed in Central Nervous System (CNS) tissues involved in processing sensory information and in generating circadian rhythms while RORγ is critical in lymph node organogenesis and thymopoeisis.
TRPA1s have been the most extensively studied subfamily; they typically contain 14 N-terminal ankyrin repeats and are believed to function as mechanical stress, temperature, and chemical sensors. TRPA1 is known to be activated by compounds such as isothiocyanate (which are the pungent chemicals in substances such as mustard oil and wasabi) and Michael acceptors (e.g. cinnamaldehyde). These compounds are capable of forming covalent chemical bonds with the protein's cysteins. Non-covalent activators of TRPA1 also exists, such as methyl salicylate, menthol, and the synthetic compound PF-4840154.
One of the subunits that exhibits the TPR motif, CDC27 has been identified to interact with mitotic checkpoint proteins such as Mad2, p55CDC and BUBR1, suggesting that it may have involvement in timing of M phase."Entrez Gene: CDC27 cell division cycle 27 homolog (S. cerevisiae)". Evidence shows that CDC27 is involved in a ternary complex with SMAD2/3 and Cdh1, which is created in response to TGFβ signalling. Because of its interaction with Cdh1 in particular, it has a potential role in determining affinity between APC and its activators Cdc20 and Cdh1.
Results suggest that they may mediate activity of the entire complex via different mechanisms at different sites. In further drosophila studies, Cdk16 and cdk23 appear to be activated via phosphorylation by Polo-like kinase 1 (Plk1) and its fission yeast counterpart, appear to bind particularly to Cdc23. The complex is understood to be regulated by activators CDC20 and Cdh1 during mitosis. Their role in degradation for cyclin B is demonstrated by a screen of Saccharomyces cerevisiae mutants defective for cyclin B degradation, which were found to have mutations in CDC16 and CDC23 genes.
Although Cdc20 and Cdh1 may serve as D and KEN box receptors, the low affinity of these co- activator–substrate interactions suggests that it is unlikely that the co- activators alone are sufficient to confer high-affinity substrate binding to the APC/CCdc20 and APC/CCdh1. Consequently, core APC/C subunits, like Apc10, contribute towards substrate association as well. In APC/C constructs lacking the Apc10/Doc1 subunit, substrates like Clb2 are unable to associate with APCΔdoc1–Cdh1, while addition of purified Doc1 to the APCΔdoc1–Cdh1 construct restores the substrate binding ability.
Several studies in the past two years have shown that in humans, Vorinostat and Entinostat increase the clinical effectiveness of exposure therapy as well, and human trials using the drugs successful in rodents are planned. In addition to research on the effectiveness of HDAC inhibitors, some researchers have suggested that histone acetyltransferase activators might have a similar effect, although not enough research has been completed to draw any conclusions. However, none of these drugs are likely to be able to replace exposure therapy or other cognitive behavioral therapy methods.
The PHD finger, approximately 50-80 amino acids in length, is found in more than 100 human proteins. Several of the proteins it occurs in are found in the nucleus, and are involved in chromatin-mediated gene regulation. The PHD finger occurs in proteins such as the transcriptional co-activators p300 and CBP, Polycomb- like protein (Pcl), Trithorax-group proteins like ASH1L, ASH2L and MLL, the autoimmune regulator (AIRE), Mi-2 complex (part of histone deacetylase complex), the co-repressor TIF1, the JARID1-family of demethylases and many more.
The picture depicts the mechanism of regulation of glnALG operon The glnALG operon is regulated by an intricate network of repressors and activators. Along with NRI and NRII, there are gene products of glnF and glnD which play a key role in this network. The expression of the glnALG operon is regulated by the NRI at three promoters: glnAp1, glnAp2 and glnLp. The initiation of transcription at glnAp1 is stimulated exclusively under carbon starvation conditions and stationary phase during which cAMP accumulates in high concentration in the cell.
Careful control of the grain size of the suspended phosphors is necessary; large grains lead to weak coatings, and small particles leads to poor light maintenance and efficiency. Most phosphors perform best with a particle size around 10 micrometers. The coating must be thick enough to capture all the ultraviolet light produced by the mercury arc, but not so thick that the phosphor coating absorbs too much visible light. The first phosphors were synthetic versions of naturally occurring fluorescent minerals, with small amounts of metals added as activators.
Allosteric regulation of an enzyme In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the allosteric site or regulatory site. Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change involving protein dynamics. Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors.
This gene encodes a member of the human ARF gene family, which is part of the Ras superfamily. The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP- ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. A pseudogene of this gene is located on chromosome 7. ARF6 can interact with βarrestin upon receptor activation.
The announcement was made after a taping day was postponed after Pat Sajak was hospitalized with emergency surgery in order to clear a blocked intestine. White hosted that taping day and the subsequent rescheduled taping day the next day. Guest letter activators were implemented during her shows hosting; the weeks of December 9 and 16 had Mickey Mouse, Minnie Mouse and other Disney characters during the Secret Santa Holiday Giveaway. The costumed Disney characters do not actually touch the game board; it was entirely automated during their guest hosting.
The biochemical purification and characterization of RNA polymerase from the bacterium Escherichia coli enabled the understanding of the mechanisms through which RNA polymerase initiates and terminates transcription, and how those processes are regulated to regulate gene expression (i.e. turn genes on and off). Following the isolation of E. coli RNA polymerase, the three RNA polymerases of the eukaryotic nucleus were identified, as well as those associated with viruses and organelles. Studies of transcription also led to the identification of many protein factors that influence transcription, including repressors, activators and enhancers.
Bone-morphogenetic-protein (BMP) signaling is responsible for the expression of the transcriptional co-activators CBP, p300, and Smad1. In the presence of Ngn1, BMPs promote neuronal differentiation in stem cells through binding of all endogenous CBP/p300/Smad1 to Ngn1, and being recruited toward the neuronal promoters, causing neuronal differentiation. In the embryonic forebrain, Ngn1 is associated with dorsal patterning and cell fate specification, with the patterning molecules and proneural proteins establishing the spatial domains of both proneural and homeodomain protein expression. This is critical for the initiation of neurogenesis.
However, high-impact AMPAR PAMs can cause motor coordination disruptions, convulsions, and neurotoxicity at sufficiently high doses, similarly to orthosteric AMPAR activators (i.e., active/glutamate site agonists). The AMPAR is one of the most highly expressed receptors in the brain, and is responsible for the majority of fast excitatory amino acid neurotransmission in the central nervous system (CNS). Considering the broad impact of the AMPARs in the CNS, selectively targeting AMPARs involved in disease is difficult, and it is thought that global enhancement of AMPARs may be associated with an intolerable level of toxicity.
Proteins involved in microbial pattern recognition include mannose receptor, complement receptors, DC-SIGN, Toll-like receptors(TLRs), the scavenger receptor, CD14, and Mac-1. PRRs can be divided into three classes: #signaling PRRs that activate gene transcriptional mechanisms that lead to cellular activation, #endocytic PRRs that function in pathogen binding and phagocytosis, and #secreted PRRs that usually function as opsonins or activators of complement. The recognition and clearance of invading microorganisms occurs through both opsonin-dependent and opsonin–independent pathways. The molecular mechanisms facilitating opsonin- dependent phagocytosis are different for specific opsonin/receptor pairs.
The delayed de-excitation of those metastable impurity states, slowed by reliance on the low-probability forbidden mechanism, again results in light emission (slow component). Phosphors are often transition-metal compounds or rare-earth compounds of various types. In inorganic phosphors, these inhomogeneities in the crystal structure are created usually by addition of a trace amount of dopants, impurities called activators. (In rare cases dislocations or other crystal defects can play the role of the impurity.) The wavelength emitted by the emission center is dependent on the atom itself and on the surrounding crystal structure.
ADP being one of the two major activators (NAD+ being the other one), acts by destabilizing the abortive complexes, and abrogating the negative cooperativity. In the absence of substrates, and with bound ADP, the catalytic cleft is in the open conformation, and the GLUD1 hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals (1NQT). This is consistent with the fact that ADP promotes aggregation in solution. When the catalytic cleft opens, R516 is rotated down on to the phosphates of ADP.
In addition to the core histones, certain HATs acetylate a number of other cellular proteins including transcriptional activators, basal transcription factors, structural proteins, polyamines, and proteins involved in nuclear import. Acetylation of these proteins can alter their ability to interact with their cognate DNA and/or protein substrates. The idea that acetylation can affect protein function in this manner has led to inquiry regarding the role of acetyltransferases in signal transduction pathways and whether an appropriate analogy to kinases and phosphorylation events can be made in this respect.
They mapped the interaction of HMGA1a and the paired homeodomain motif within Crx and showed that these interactions help recruit such transcriptional activators to the promoter/enhancer. Using transgenic mouse technology, they also showed (concurrently and independently of Alfredo Fusco), that fusion proteins between HMGA2 and other C terminal peptides (following chromosomal translocation) can drive the development of lipomas and generate obese mice. Further contributions in the field include the mapping of the HMGA2 promoter/enhancer. More recently, his laboratory determined the role of beta-chemokines in mast cell-dependent inflammation in the ocular surface.
In the T state, enzyme conformation shifts slightly such that the space previously taken up by the Arg162 is replaced with Glu161. This swap in positions between adjacent amino acid residues inhibits the ability of F6P to bind the enzyme. Allosteric activators such as AMP and ADP bind to the allosteric site as to facilitate the formation of the R state by inducing structural changes in the enzyme. Similarly, inhibitors such as ATP and PEP bind to the same allosteric site and facilitate the formation of the T state, thereby inhibiting enzyme activity.
These are typically allosterically-controlled enzymes, tightly locked into an inactive state by multiple mechanisms. The first step en route to their activation consist of relieving their autoinhibition by a smaller ligand (such as Ras for c-Raf, GADD45 for MEKK4 or Cdc42 for MLK3). This commonly (but not always) happens at the cell membrane, where most of their activators are bound (note that small G-proteins are constitutively membrane-associated due to prenylation). That step is followed by side-to-side homo- and heterodimerisation of their now accessible kinase domains.
PAK1 activity is stimulated by a large number of upstream activators and signals, ranging from EGF, heregulin-beta 1, VEGF, basic fibroblast growth factor, platelet-derived growth factor, estrogen, lysophosphatidic acid, phosphoinositides, ETK, AKT, JAK2, ERK, casein kinase II, Rac3, chemokine (C-X-C motif) ligand 1, breast cancer anti-estrogen resistance 3, Kaposi's sarcoma-associated herpesvirus-G protein-coupled receptor, ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl transferase V, B-Raf proto-oncogene, casein kinase 2-interacting protein 1, and filamin A.
And since the energy gap between the ground level and this excited state matches well with the "ladder" gaps in the common activator ions, resonant energy transfers between the two dopant types. Typical UCNPs are doped with approximately 20 mol% sensitizer ions and less than 2 mol% activator ions. These concentrations allow adequate distance between activators, avoiding cross-relaxation, and still absorb enough excitation radiation through the sensitizers to be efficient. Currently, other types of sensitizers are being developed to increase the spectral range available for upconversion, such as semi-conductor nanocrystal-organic ligand hybrids.
The package of gun control legislation supported by Northam in 2020 included an eighth bill that did not pass: it would have banned assault weapons, high-capacity magazines, trigger activators, and silencers. The ban on assault weapons would not have applied to firearms already owned in Virginia. The bill limiting handgun purchases to one-a-month reinstates a law that had been repealed in 2012 under then-governor Bob McDonnell; it had originally been passed in 1993 under then-governor Douglas Wilder. Virginia was the nineteenth state to pass a red flag law.
Antagonism of TGF-ß also further reduced MFS symptoms where it helped muscle regeneration, architecture and strength, pulmonary alveolar septation and mitral valve morphology. LLC that fails to be removed from the ECM is more vulnerable to be activated in a protease-dependent or independent manner. MMP2 and MMP9 are select TGF-ß activators and ligands and are found in higher levels in the tissues of patients affected with MFS. TGF-ß in its complex and free-form can leach into the circulation due to the mutated ECM sequestration and increased LLC activation.
DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene. This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA- directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit.
In eukaryotes, RNA transcription is a tightly regulated process. NcRNAs can target different aspects of this process, targeting transcriptional activators or repressors, different components of the transcription reaction including RNA polymerase (RNAP) II and even the DNA duplex to regulate gene transcription and expression. In combination these ncRNAs may comprise a regulatory network that, including transcription factors, finely control gene expression in complex eukaryotes. NcRNAs modulate the function of transcription factors by several different mechanisms, including functioning themselves as co-regulators, modifying transcription factor activity, or regulating the association and activity of co-regulators.
The same antigen-specific antibody is secreted and it can feedback-suppress, or promote negative signaling. This negative signaling is being provided by FcγRIIB.: Experiments using B cell deletion mutants and dominant-negative enzymes have firmly established an important role for SH2-domain-containing inositol 5-phosphatase (SHIP) in negative signaling. Negative signaling through SHIP appears to inhibit the Ras pathway through SH2 domain competition with Grb2 and Shc and may involve consumption of intracellular lipid mediators that act as allosteric enzyme activators or that promote entry of extracellular Ca2+.
The main physiological functions of cathepsin D consist of metabolic degradation of intracellular proteins, activation and degradation of polypeptide hormones and growth factors, activation of enzymatic precursors, processing of enzyme activators and inhibitors, brain antigen processing and regulation of programmed cell death. Cathepsin D can also be found in the extracellular space and it is one of the few cathepsins, that shows some activity at neutral pH. It is able to activate the growth factors VEGF-C and VEGF-D, which might partly explain its relevance for tumor progression.
This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. It is an important component of cAMP-mediated signal transduction during the spermatogenetic cycle, as well as other complex processes. Alternative promoter and translation initiation site usage allows this gene to exert spatial and temporal specificity to cAMP responsiveness. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene, with some of them functioning as activators and some as repressors of transcriptnhunion.
Nanomolar concentrations of endorepellin inhibits EC migration and angiogenesis in different in vitro and in vivo models by blocking EC adhesion to various substrate such as fibronectin and type I collagen. Endogenous inhibitors or activators generated by proteolytic degradation of larger proteins mostly from the ECM have proven to contribute to the regulation of tumor growth and angiogenesis. This article mentions only a small fraction of the known proteolytic fragments which alter EC behavior and function during angiogenesis. This abundance has garnered increased attention because of their potential for anti-angiogenic and anti-cancer therapies.
Since malate is formed in the next step of the CAM and cycles after PEP carboxylase catalyses the condensation of CO2 and PEP to oxaloacetate, this works as a feedback inhibition pathway. Oxaloacetate and aspartate are easily inter-convertible through a transaminase mechanism; thus high concentrations of aspartate are also a pathway of feedback inhibition of PEP carboxylase. The main allosteric activators of PEP carboxylase are acetyl- CoA and fructose-1,6-bisphosphate (F-1,6-BP). Both molecules are indicators of increased glycolysis levels, and thus positive feed-forward effectors of PEP carboxylase.
In addition to cell signaling, the mTOR pathway also plays a role in beta cell growth leading to insulin secretion. High glucose in the blood begins the process of the mTOR signaling pathway, in which leucine plays an indirect role. The combination of glucose, leucine, and other activators cause mTOR to start signaling for the proliferation of beta cells and the secretion of insulin. Higher concentrations of leucine cause hyperactivity in the mTOR pathway, and S6 kinase is activated leading to inhibition of insulin receptor substrate through serine phosphorylation.
To overcome the limitation of the dCas9-VP64 gene activation system, the dCas9-SAM system was developed to incorporate multiple transcriptional factors. Utilizing MS2, p65, and HSF1 proteins, dCas9-SAM system recruits various transcriptional factors working synergistically to activate the gene of interest.The dCas-SAM system uses msgRNA that has attached aptamers for different transcriptional factors (MS2,p65 and HSF1) to bind. In order to assemble different transcriptional activators, the dCas9-SAM system uses a modified single guide RNA (sgRNA) that has binding sites for the MS2 protein.
Nagai H, Yasumoto T, Hokama Y. Aplysiatoxin and debromoaplysiatoxin as the causative agents of a red alga Gracilaria coronopifolia poisoning in Hawaii. Toxicon. 1996 Jul;34(7):753-61. While this action has a tumour-promoting effect, protein kinase C activation can be medically beneficial for some other applications, and synthetic analogues of aplysiatoxin have been researched for anti-cancer effects.Watanabe M, Kawase Y, Tanabe J, Min KR, Mue S, Ohuchi K. Suppression of interleukin-1 alpha production by protein kinase C activators in human vascular endothelial cells.
Some of these sensations may be referred to as spiciness, pungency, or piquancy. Chemesthetic sensations sometimes arise by direct chemical activation of ion channels on sensory nerve fibers, for example of transient receptor potential channels including those of the TRPV, TRPA or TRPM subtypes. Alternatively, irritant chemicals may activate cells of the epithelium to release substances that indirectly activate the nerve fibers. The respiratory passages, including the nose and trachea, possess specialized cells called solitary chemosensory cells which release acetylcholine or other activators to excite nearby nerve fibers.
The graphic display of an operon contains all the genes of its different transcription units, as well as all the regulatory elements involved in the transcription and regulation of those TUs. The graphic display of a TU will always contain only one promoter -when known- with the binding sites that regulate its activity, followed by the transcribed genes. Note that dual sites are frequently displayed at a TU as repressors or activators. This is because the site will have a particular effect on the promoter of that TU.
Like other vampire bats, their saliva contains plasminogen activators, which rapidly dissolves the host's blood clots that form during feeding; platelet aggregation inhibitors, which prevent the formation of blood clots; and other anticoagulants, which also prevent blood clots. These compounds in their saliva are especially effective on birds. Birds are their preferred prey source, but they will also prey on mammals such as goats and cattle. While it can transmit rabies, this appears to be relatively uncommon: the only reports of rabies transmission from this species are from Trinidad.Constantine, D.C. 1988.
It may also happen that a repressor may function by allosteric competition against a determined activator to repress gene expression: overlapping DNA-binding motifs for both activators and repressors induce a physical competition to occupy the site of binding. If the repressor has a higher affinity for its motif than the activator, transcription would be effectively blocked in the presence of the repressor. Tight regulatory control is achieved by the highly dynamic nature of transcription factors. Again, many different mechanisms exist to control whether a transcription factor is active.
CK is often determined routinely in a medical laboratory. It used to be determined specifically in patients with chest pain but this test has been replaced by troponin. Normal values at rest are usually between 60 and 400 IU/L, where one unit is enzyme activity, more specifically the amount of enzyme that will catalyze 1 μmol of substrate per minute under specified conditions (temperature, pH, substrate concentrations and activators.) This test is not specific for the type of CK that is elevated. Creatine kinase in the blood may be high in health and disease.
ADP-ribosylation factor 4 (ARF4) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 5 ARF proteins and 11 ARF-like proteins and constitute 1 family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1 and ARF3), class II (ARF4 and ARF5) and class III (ARF6). The members of each class share a common gene organization.
Gene expression is regulated by numerous types of proteins that directly or indirectly influence transcription by RNA Polymerase II. As opposed to transcriptional activators or repressors that selectively activate or repress specific genes, amplifiers of transcription act globally on the set of initially expressed genes. Several known regulators of transcriptional amplification have been characterized including the oncogene Myc., the Rett syndrome protein MECP2, and the BET bromodomain protein BRD4. In particular, the Myc protein amplifies transcription by binding to promoters and enhancers of active genes where it directly recruits the transcription elongation factor P-TEFb.
Heat stress has been shown to cause problems in mitochondrial functions and can result in oxidative damage. Activators of heat stress receptors and defenses are thought to be related to ROS. Heat is another thing that plants can deal with if they have the proper pretreatment. This means that if the temperature gradually warms up the plants are going to be better able to cope with the change. A sudden long temperature increase could cause damage to the plant because their cells and receptors haven’t had enough time to prepare for a major temperature change.
The saposin domains refers to two evolutionally-conserved protein domains found in saposin and related proteins (SAPLIP). Saposins are small lysosomal proteins that serve as activators of various lysosomal lipid-degrading enzymes. They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. All mammalian saposins are synthesized as a single precursor molecule (prosaposin) which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction.
This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator.
Due to the invasive nature of invadopodia in cancer cells, research has focused on targeting invadopodia as a potential therapeutic target to inhibit metastasis. Inhibiting invadopodia formation by targeting Src kinase with Saracatanib in a chicken model system showed a decreased incidence of invadopodia and decreased cancer extravasation. In mice, inhibiting invadopodia formation directly, through RNAi against tks4 or tks5, significantly reduced cancer extravasation. Screening for drug activators and inhibitors of invadopodia revealed that Cdc5 can be a target for inhibiting invadopodia formation and also that, paradoxically, paclitaxel, a drug commonly used to treat cancer, induces invadopodia formation.
Aside from acetic anhydride, trifluoroacetic anhydride and trifluoromethanesulfonic anhydride have been employed as activators. Common nucleophiles besides acetates are arenes, alkenes, amides, and phenols. The usage of α-acyl sulfoxides and Lewis acids, such as TiCl4 and SnCl4, allow the reaction to proceed at lower temperatures (0 °C). Thionyl chloride can be used in place of acetic anhydride to trigger the elimination for forming the electrophilic intermediate and supplying chloride as the nucleophile to give an α-chloro-thioether: Example of the Pummerer rearrangement using thionyl chloride Other anhydrides and acyl halides can give similar products.
Unwanted side reactions such as threonine and asparagine production can occur if a buildup of intermediates occurs, so scientists have developed mutant strains of C. glutamicum through PCR engineering and chemical knockouts to ensure production of side-reaction enzymes are limited. Many genetic manipulations conducted in industry are by traditional cross-over methods or inhibition of transcriptional activators. Expression of functionally active human epidermal growth factor has been brought about in C. glutamicum, thus demonstrating a potential for industrial-scale production of human proteins. Expressed proteins can be targeted for secretion through either the general secretory pathway or the twin-arginine translocation pathway.
Activated clotting time (ACT), also known as activated coagulation time, is a test of coagulation. labtestsonline.org > ACT This article was last reviewed on March 20, 2008. This page was last modified on March 30, 2010 The ACT test can be used to monitor anticoagulation effects, such as high-dose heparin before, during, and shortly after procedures that require intense anticoagulant administration, such as cardiac bypass, interventional cardiology, thrombolysis, extra-corporeal membrane oxygenation (ECMO), and continuous dialysis. It measures the seconds needed for whole blood to clot upon activation of the intrinsic pathway by the addition of factor XII activators.
12-O-Tetradecanoylphorbol-13-acetate (TPA), also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate (PMA), is a diester of phorbol and a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein kinase C (PKC). The effects of TPA on PKC result from its similarity to one of the natural activators of classic PKC isoforms, diacylglycerol. TPA is a small molecule drug. In ROS biology, superoxide was identified as the major reactive oxygen species induced by TPA/PMA but not by ionomycin in mouse macrophages.
The lacUV5 promoter is a mutated promoter from the Escherichia coli lac operon which is used in molecular biology to drive gene expression on a plasmid. lacUV5 is very similar to the classical lac promoter, containing just 2 base pair mutations in the -10 hexamer region, compared to the lac promoter. LacUV5 is among the most commonly used promoters in molecular biology because it requires no additional activators and it drives high levels of gene expression. The lacUV5 promoter sequence conforms more closely to the consensus sequence recognized by bacterial sigma factors than the traditional lac promoter does.
When securin undergoes ubiquitination by the APC/C and releases separase, which degrades cohesin, sister chromatids become free to move to opposite poles for anaphase. The APC/C also targets the mitotic cyclins for degradation, resulting in the inactivation of M-CDK (mitotic cyclin-dependent kinase) complexes, promoting exit from mitosis and cytokinesis Unlike the SCF, activator subunits control the APC/C. Cdc20 and Cdh1 are the two activators of particular importance to the cell cycle. These proteins target the APC/C to specific sets of substrates at different times in the cell cycle, thus driving it forward.
Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. DNA copy-number alterations that contribute to increased conversion of the oncogenes Gli1–3 into transcriptional activators by the Hedgehog signaling pathway are included in a genome-wide pattern, which was found to be correlated with an astrocytoma patient's outcome. There is evidence that the autosomal dominant disorder Greig cephalopolysyndactyly syndrome (GCPS) that affects limb and craniofacial development in humans is caused by a translocations within the GLI3 gene.
CRISPRi and CRISPRa use a deactivated Cas9 (dCas9) enzyme that cannot cut DNA, but can deliver transcriptional activators and repressors to modulate desired gene expression with high precision. Currently, off-target effects of CRISPRi are minimal, and show a reduced response and sensitivity to single-base mismatches. Importantly, when non-specific effects do inevitably occur they are reversible, time-dependent, and less damaging than DNA editing, making them effective alternatives that can limit the off-target burden when possible. CRISPR-cas13b, using a type IV CRISPR-Cas system (as opposed to the commonly used type II) can target and edit specific RNA sequences.
5 The regulators of a given operon, including repressors, corepressors, and activators, are not necessarily coded for by that operon. The location and condition of the regulators, promoter, operator and structural DNA sequences can determine the effects of common mutations. Operons are related to regulons, stimulons and modulons; whereas operons contain a set of genes regulated by the same operator, regulons contain a set of genes under regulation by a single regulatory protein, and stimulons contain a set of genes under regulation by a single cell stimulus. According to its authors, the term "operon" is derived from the verb "to operate".
Friedel–Crafts alkylation involves the alkylation of an aromatic ring with an alkyl halide using a strong Lewis acid, such as aluminium chloride, ferric chloride, or other MXn reagent, as catalyst. The general mechanism for tertiary alkyl halides is shown below. :Mechanism for the Friedel Crafts alkylation For primary (and possibly secondary) alkyl halides, a carbocation-like complex with the Lewis acid, [R(+)\---(X--- MXn)(–)] is more likely to be involved, rather than a free carbocation. This reaction suffers from the disadvantage that the product is more nucleophilic than the reactant because alkyl groups are activators for the Friedel–Crafts reaction.
Characters are normally used only to represent the team a player is using, but they are also used as activators. A player's team consists of four characters: three on the front line, and one in reserve, who moves up to the front only when one of the other characters is KO'd. Power cards Power cards each consist of a number from 1 to 8 and a type, Energy, Fighting, Strength, Intellect, Multi-Power, or Any-Power. Power cards can be used as an attack of the level of the number, or as a defense of the level of the number.
In 1995, after working at Burroughs Wellcome for over 26 years, and rising to the rank of associate division director, Rideout joined Inspire Pharmaceuticals (acquired by Merck in 2011) as Director of Chemistry. She subsequently had a number of promotions within the company: to Senior Director of Discovery in June 1996, Vice President in January 1998, and Senior Vice President of Discovery in February 2000. At Inspire Pharmaceuticals, she continued researching nucelosides but now as activators (agonists) instead of inhibitors. In addition to their role in the biosynthesis of nucleic acids, nucleotides can serve as important signaling molecules including through activating purinergic receptors.
It is described as a "high-impact" AMPAR PAM, unlike so-called "low-impact" AMPAR PAMs like CX-516 and its cogener farampator (CX-691, ORG-24448). In animals, low doses of BIIB-104 have been found to enhance cognition and memory, whereas higher doses produce motor coordination disruptions and convulsions. The same effects, as well as neurotoxicity at higher doses, have been observed with orthosteric and other high-impact allosteric AMPAR activators. In healthy volunteers, BIIB-104 has been found to significantly reduce ketamine-induced deficits in verbal learning and working memory without attenuating ketamine- induced psychotomimetic effects.
For example, the downregulation of the expression of proneural gene ngn2 in the spinal cord represses oligodendrocyte differentiation. In the context of restricted glial progenitors, proneural genes might have functions that are distinct from their better-characterized role in lineage specification, perhaps in the differentiation of glial lineages. Sun and colleagues showed that proneural ngn1 inhibits gliogenesis by binding transcriptional co-activators like CBP/Smad1 or p300/Smad1 preventing the transcription of glialdifferentiation genes. On the other hand, the Notch signaling pathway is capable of promoting gliogenesis in stem cells through the inhibition of proneural genes, such as mash1 and neurogenins.
Price's research centers around the molecular mechanisms of circadian rhythms, using Drosophila melanogaster as model organisms. He is specifically interested in the role of protein kinases in clock function, and using forward genetics screens Price has contributed to the identification and characterization of many critical elements of the Drosophila circadian clock. The molecular circadian clock of D. melanogaster can be described as a feedback loop of transcription and translation, in which the proteins CLOCK and CYCLE act as transcriptional activators of the period and timeless genes. Their protein products, PER and TIM, respectively, dimerize and translocate to the nucleus after phosphorylation by DBT.
In addition to roles in mediating cell survival, studies by Mark Mattson and others have shown that NF-κB has diverse functions in the nervous system including roles in plasticity, learning, and memory. In addition to stimuli that activate NF-κB in other tissues, NF-κB in the nervous system can be activated by Growth Factors (BDNF, NGF) and synaptic transmission such as glutamate. These activators of NF-κB in the nervous system all converge upon the IKK complex and the canonical pathway. Recently there has been a great deal of interest in the role of NF-κB in the nervous system.
Because NF-κB controls many genes involved in inflammation, it is not surprising that NF-κB is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis and others. It is important to note though, that elevation of some NF-κB activators, such as osteoprotegerin (OPG), are associated with elevated mortality, especially from cardiovascular diseases. Elevated NF-κB has also been associated with schizophrenia. Recently, NF-κB activation has been suggested as a possible molecular mechanism for the catabolic effects of cigarette smoke in skeletal muscle and sarcopenia.
Supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of tumour cells and their environment, for example, dimerisation partners, co-activators and promoter architecture. It is possible that the tumor suppressing activity is due to a proapoptotic function. The exact mechanism by which c-Fos contributes to apoptosis is not clearly understood, but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and might induce apoptosis through the p38 MAP kinase pathway.
The stereotypic inflammatory response provoked by toll Like-Receptor activation has prompted speculation that endogenous activators of toll-like receptors might participate in autoimmune diseases. TLRs have been suspected of binding to host molecules including fibrinogen (involved in blood clotting), heat shock proteins (HSPs), HMGB1, extracellular matrix components and self DNA (it is normally degraded by nucleases, but under inflammatory and autoimmune conditions it can form a complex with endogenous proteins, become resistant to these nucleases and gain access to endosomal TLRs as TLR7 or TLR9). These endogenous ligands are usually produced as a result of non-physiological cell death.
Mediator of RNA polymerase II transcription subunit 29 (Med29) is a transcription suppressor that in humans is encoded by the MED29 gene. It represents subunit MED29 of the Mediator complex. Med29, along with Med11 and Med28 in mammals, is part of the core head-region of the Mediator complex. Med29 is the apparent orthologue of the Drosophila melanogaster Intersex protein (IXL), which interacts directly with, and functions as a transcriptional coactivator for, the DNA-binding transcription factor Doublesex, so it is likely that mammalian Med29 serves as a target for one or more DNA-binding transcriptional activators.
Alternative transcripts of this gene have been found, but their full-length natures have not been determined. Stimulation of PAK1 activity is accompanied by a series of cellular processes that are fundamental to living systems. Being a nodular signaling molecule, PAK1 operates to converging station of a large number of signals triggered by proteins on the cell surface as well as upstream activators, and translates into specific phenotypes. At the biochemical level, these activities are regulated by the ability of PAK1 to phosphorylate its effector interacting substrates, which in-turn set-up a cascade of biochemical events cumulating into a cellular phenotypic response.
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein mediates the signal transduction triggered by various cell ligands, such as IL2, IL4, CSF1, and different growth hormones. It has been shown to be involved in diverse biological processes, such as TCR signaling, apoptosis, adult mammary gland development, and sexual dimorphism of liver gene expression.
Normal thyroid hormone function requires normal thyroid hormone transport across cell membrane, appropriate deiodination, thyroid hormone nuclear receptor, thyroid hormone response elements, co-activators, co-repressors, and normal histone acetylation. Any abnormalities in this chain can result in thyroid hormone resistance and it has not been as well studied as the various forms of insulin resistance. The most well known cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented. Mutations in MCT8 and SECISBP2 have also been associated with this condition.
Tree injection—also known as trunk injection or stem injection,—is a method of targeting a precise application of pesticides, plant resistance activators, or fertilizers into the xylem vascular tissue of a tree with the purpose of protecting the tree from pests, or to inject nutrients to correct for nutrient deficiencies. This method largely relies on harnessing the tree's vascular system to translocate and distribute the active compounds into the wood, canopy and roots where protection or nutrition is needed. Tree injection is currently the most popular method for control of damaging insects, pathogens, and nematodes in landscape tree care.
Phosphorylated tyrosine residues act as binding sites for intracellular signal activators such as Ras. The Ras-Raf-MAPK pathway is a major signalling route for the ErbB family, as is the PI3-K/AKT pathway, both of which lead to increased cell proliferation and inhibition of apoptosis. Genetic Ras mutations are infrequent in breast cancer but Ras may be pathologically activated in breast cancer by overexpression of ErbB receptors.Hollestelle A, Elstrodt F, Nagel J, Kallemeign W, Schutte M. (2007). “Phosphatidylinositol-3-OH Kinase or RAS Pathway Mutations in Human Breast Cancer Cell Lines”. Molecular Cancer Research, 5: 195-201 doi: 10.1158/1541-7786.
Although dCas9 lacks endonuclease activity, it is still capable of binding to its guide RNA and the DNA strand that is being targeted because such binding is managed by other domains. This alone is often enough to attenuate if not outright block transcription of the targeted gene if the gRNA positions dCas9 in a way that prevents transcriptional factors and RNA polymerase from accessing the DNA. However, this ability to bind DNA can also be exploited for activation since dCas9 has modifiable regions, typically the N and C terminus of the protein, that can be used to attach transcriptional activators.
ADP-ribosylation factor 5 is a protein that in humans is encoded by the ARF5 gene. ADP-ribosylation factor 5 (ARF5) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 6 ARF proteins and 11 ARF-like proteins and constitute 1 family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2, and ARF3), class II (ARF4 and ARF5) and class III (ARF6).
T-box transcription factor 2 Tbx2 is a transcription factor that is encoded by the Tbx2 gene on chromosome 17q21-22 in humans. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. Tbx2 and Tbx3 are the only T-box transcription factors that act as transcriptional repressors rather than transcriptional activators, and are closely related in terms of development and tumorigenesis. This gene plays a significant role in embryonic and fetal development through control of gene expression, and also has implications in various cancers.
The enzymatic activity of oxygen sensor dioxygenase PHD is dependent on oxygen level as it requires oxygen as one of its main substrates to transfer to the proline residue of HIF1A. The hydroxylated proline residue of HIF1A is then recognized and buried in the hydrophobic core of von Hippel-Lindau tumor suppressor protein (VHL), which itself is part of a ubiquitin ligase enzyme. The hydroxylation of HIF1A proline residue also regulates its ability to associate with co-activators under hypoxia. Function of HIF1A gene can be effectively examined by siRNA knockdown based on an independent validation.
Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1). The other PAI, plasminogen activator inhibitor-2 (PAI-2) is secreted by the placenta and only present in significant amounts during pregnancy.
Due to this, lacUV5 recruits RNA Polymerase more effectively, thus leading to higher transcription of target genes. Additionally, unlike the lac promoter, lacUV5 works independently of activator proteins or other cis regulatory elements (apart from the -10 and -35 promoter regions). While no activators are required, lacUV5 promoter expression can be regulated by the LacI repressor and can be induced with IPTG, which is an effective inducer of protein expression when used in the concentration range of 100μM to 1.5mM. Due to this control, the lacUV5 promoter is commonly found on expression plasmids and is used when controllable but high levels of a product are desired.
According to PubMed, Schlessinger has authored over 450 scientific original and review articles in the areas of pharmacology, molecular biology, biochemistry, and structural biology, mostly on tyrosine kinase signaling. Tyrosine kinase signaling plays a critical role in the control of many cellular processes including cell proliferation, differentiation, metabolism, as well as cell survival and migration. Tyrosine kinases play a particularly important role in cancer, and several agents that block their activity are now used as anti-cancer drugs, such as Imatinib or Gleevec. Among his contributions are the findings that cell surface receptors with tyrosine kinase activity signal across membrane by forming dimers when they bind to their growth factor activators.
Cryptochrome is one of the four groups of mammalian clock genes/proteins that generate a transcription-translation negative-feedback loop (TTFL), along with Period (PER), CLOCK, and BMAL1. In this loop, CLOCK and BMAL1 proteins are transcriptional activators, which together bind to the promoters of the Cry and Per genes and activate their transcription. The CRY and PER proteins then bind to each other, enter the nucleus, and inhibit CLOCK-BMAL1-activated transcription. In mice, Cry1 expression displays circadian rhythms in the suprachiasmatic nucleus, a brain region involved in the generation of circadian rhythms, with mRNA levels peaking during the light phase and reaching a minimum in the dark.
Specificity of APC ligases are proposed to be controlled by incorporation of specificity factors into the ligase complex, instead of substrate phosphorylation. i.e.: The subunit, CDC20 allows APC to degrade substrates such as anaphase inhibitors (Pdsp1) at the beginning of anaphase, on the other hand when CDC20 is substituted for specificity factor Hct1, APC degrades a different set of substrates, particularly mitosis cyclins in late anaphase. Activators CDC20 and Cdh1 are of particular significance and are the most widely studied and familiar of the APC/C subunits. The catalytic core of the APC/C consists of the cullin subunit Apc2 and RING H2 domain subunit Apc11.
The production of alternatively spliced mRNAs is regulated by a system of trans-acting proteins that bind to cis-acting sites on the primary transcript itself. Such proteins include splicing activators that promote the usage of a particular splice site, and splicing repressors that reduce the usage of a particular site. Mechanisms of alternative splicing are highly variable, and new examples are constantly being found, particularly through the use of high-throughput techniques. Researchers hope to fully elucidate the regulatory systems involved in splicing, so that alternative splicing products from a given gene under particular conditions ("splicing variants") could be predicted by a "splicing code".
The structure of a transcription factory appears to be determined by cell type, transcriptional activity of the cell and also the method of technique used to visualise the structure. The generalised view of a transcription factory would feature between 4 – 30 RNA polymerase molecules and it is thought that the more transcriptionally active a cell is, the more polymerases that will be present in a factory in order to meet the demands of transcription. The core of the factory is porous and protein rich, with the hyperphosphorylated, elongating form polymerases on the perimeter. The type of proteins present include: ribonucleoproteins, co-activators, transcription factors, RNA helicase and splicing and processing enzymes.
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non- GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including integrins, receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these classes whose primary function is as part of GPCR- independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs.
Neurotensin shares significant sequence similarity in its 6 C-terminal amino acids with several other neuropeptides, including neuromedin N (which is derived from the same precursor). This C-terminal region is responsible for the full biological activity, the N-terminal portion having a modulatory role. The neurotensin/neuromedin N precursor can also be processed to produce large 125–138 amino acid peptides with the neurotensin or neuromedin N sequence at their C terminus. These large peptides appear to be less potent than their smaller counterparts, but are also less sensitive to degradation and may represent endogenous, long-lasting activators in a number of pathophysiological situations.
The cytoplasmic domains of the EpoR contain a number of phosphotyrosines that are phosphorylated by Jak2 and serve as docking sites for a variety of intracellular pathway activators and Stats (such as Stat5). In addition to activating Ras/AKT and ERK/MAP kinase, phosphatidylinositol 3-kinase/AKT pathway and STAT transcription factors, phosphotyrosines also serve as docking sites for phosphatases that negatively affect EpoR signaling in order to prevent overactivation that may lead to such disorders as erythrocytosis. In general, the defects in the erythropoietin receptor may produce erythroleukemia and familial erythrocytosis. Mutations in Jak2 kinases associated with EpoR can also lead to polycythemia vera.
GLI1 was originally isolated from a glioma tumour and has been found to be up regulated in many tumors including muscle, brain and skin tumors such as Basal cell carcinoma (BCC). DNA copy- number alterations that contribute to increased conversion of the oncogenes Gli1–3 into transcriptional activators by the Hedgehog signaling pathway are included in a genome-wide pattern, which was found to be correlated with an astrocytoma patient’s outcome. Shh and the Gli genes are normally expressed in hair follicles, and skin tumours expressing Gli1 may arise from hair follicles. The level of Gli1 expression correlates with the tumor grade in bone and soft tissue sarcomas.
Selective gene knockdown of known components of the human circadian clock demonstrates both active compensatory mechanisms and redundancy are used to maintain function of the clock. How these self- sustained cellular clocks achieve multicellular integration is largely obscure, but astrocytes alone can drive the molecular oscillations in the SCN and circadian behavior in mice. Several mammalian clock genes have been identified and characterized through experiments on animals harboring naturally occurring, chemically induced, and targeted knockout mutations, and various comparative genomic approaches. The majority of identified clock components are transcriptional activators or repressors that modulate protein stability and nuclear translocation, and create two interlocking feedback loops.
The scheme was initiated by Adriaan Nieuwoudt after his grandmother showed him a milk culture she used as a skin product. He turned the culture into a work- from-home business by selling dried plants that would produce thick milk for R500, which would produce 10 jars of culture a week. In return he paid R10 per envelope or R100 per week for producers who sent him a teaspoon of the culture, making for break-even within five weeks. The dried product sent back by activation kit buyers were ground up, without first being removed from the envelopes in which it was shipped – and resold as new activators.
Krynac 33110 F nitrile rubber bales Emulsifier (soap), acrylonitrile, various butadiene monomers (including 1,3-butadiene, 1,2-butadiene), radical generating activators, and a catalyst are added to polymerization vessels in the production of hot NBR. Water serves as the reaction medium within the vessel. The tanks are heated to 30–40 °C to facilitate the polymerization reaction and to promote branch formation in the polymer. Because several monomers capable of propagating the reaction are involved in the production of nitrile rubber the composition of each polymer can vary (depending on the concentrations of each monomer added to the polymerization tank and the conditions within the tank).
PCAF and p300/CBP are the main HATs that have been observed to acetylate a number of non-histone proteins. For PCAF, these include the non- histone chromatin (high-mobility group (HMG)) proteins HMG-N2/HMG17 and HMG-I(Y), the transcriptional activators p53, MyoD, E2F(1-3), and HIV Tat, and the general transcription factors TFIIE and TFIIF. Other proteins include CIITA, Brm (chromatin remodeler), NF-κB (p65), TAL1/SCL, Beta2/NeuroD, C/EBPβ, IRF2, IRF7, YY1, KLF13, EVI1, AME, ER81, and the androgen receptor (AR). PCAF has also been observed to acetylate c-MYC, GATA-2, retinoblastoma (Rb), Ku70, and E1A adenovirus protein.
Lanthanide dopants are used as activator ions because they have multiple 4f excitation levels and completely filled 5s and 5p shells, which shield their characteristic 4f electrons, thus producing sharp f-f transition bands. These transitions provide substantially longer lasting excited states, since they are Laporte forbidden, thus allowing longer time necessary for the multiple excitations required for upconversion. The concentration of activator ions in UCNPs is also critically important, as this determines the average distance between the activator ions and therefore affects how easily energy is exchanged. If the concentration of activators is too high and energy transfer too facile, cross-relaxation may occur, reducing emission efficiency.
The following standard prostaglandins have the following relative potencies in binding to and activating EP1: PGE2≥PGE1>PGF2alpha>PGD2. The receptor binding affinity Dissociation constant Kd (i.e. ligand concentration needed to bind with 50% of available EP1 receptors) is ~20 nM and that of PGE1 ~40 for the mouse receptor and ~25 nM for PGE2 with the human receptor. Because PGE2 activates multiple prostanoid receptors and has a short half-life in vivo due to its rapidly metabolism in cells by omega oxidation and beta oxidation], metabolically resistant EP1-selective activators are useful for the study of EP1's function and could be clinically useful for the treatment of certain diseases.
GRKs reside normally in an inactive state, but their kinase activity is stimulated by binding to a ligand-activated GPCR (rather than by regulatory phosphorylation as is common in other AGC kinases). Because there are only seven GRKs (only 4 of which are widely expressed throughout the body) but over 800 human GPCRs, GRKs appear to have limited phosphorylation site selectivity and are regulated primarily by the GPCR active state. G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Phosphorylated serine and threonine residues in GPCRs act as binding sites for and activators of arrestin proteins.
In enzymology, a glycylpeptide N-tetradecanoyltransferase () is an enzyme that catalyzes the chemical reaction :tetradecanoyl-CoA + glycylpeptide \rightleftharpoons CoA + N-tetradecanoylglycylpeptide Thus, the two substrates of this enzyme are tetradecanoyl-CoA and glycylpeptide, whereas its two products are CoA and N-tetradecanoylglycylpeptide. It participates in the N-Myristoylation of proteins, and in vertebrates there are two isoenzymes NMT1 and NMT2. Besides tetradecanoyl-CoA, this enzyme is also capable of using modified versions of this subtrate. In human retina, an even wider range of fatty acids, including 14:1 n–9, 14:2n–6, and 12:0, are accepted by the enzyme and grafted onto guanylate cyclase activators.
The thrust reversers—which are located behind the engine and direct the exhaust forward to slow the aircraft down quickly after landing (see image)—were found seriously damaged, but the hydraulic mechanism of the left engine was set for reverse thrust, while the right one was set for forward thrust. The investigation was unable to determine if the thrust reversers were intentionally activated and later deactivated. It was important for the investigation to establish the position of the mechanical activators on the flaps, since their lack of deployment was a fundamental cause of the accident. A special investigation was carried out to establish what had happened with the flaps.
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis.
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to translocate to the Golgi apparatus, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu (PTPRM) is capable of dephosphorylating PLCG1.
IGF-1 binds to at least two cell surface receptor tyrosine kinases: the IGF-1 receptor (IGF1R), and the insulin receptor. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of many cell types in many tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death . The IGF-1 receptor seems to be the "physiologic" receptor because it binds IGF-1 with significantly higher affinity than insulin receptor does.
The activated Dvl associates with Axin and prevents GSK3β and casein kinase 1α (CK1α) from phosphorylating critical substrates, such as β-catenin. Phosphorylation of β-catenin marks the protein for ubiquitylation and rapid degradation by proteasomes. Thus, the binding of Wnt to the receptor results in a non-phosphorylated form of β-catenin which localizes to the nucleus and, after displacing the Groucho corepressor protein, forms a complex with Tcf/Lef transcription factors and co-activators (such as CREB binding protein) and induces the expression of downstream target genes. β-catenin is actively stabilized in over 50% of breast cancers and its nuclear localization correlates with poor patient prognosis.
ADP-ribosylation factor 3 (ARF3) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 6 ARF proteins and 11 ARF-like proteins and constitute 1 family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2, and ARF3), class II (ARF4 and ARF5) and class III (ARF6) and members of each class share a common gene organization. The ARF3 gene contains five exons and four introns.
Similarly to other HES proteins, Hes1 has been shown to interact with the co-repressors encoded by the Transducin-like E(spl) (TLE) genes and the Groucho-related gene (Grg), both homologs of the Drosophila groucho. Because Groucho in Drosophila inhibits transcription by recruiting histone deacetylase, it is likely that a Hes-Groucho complex actively blocks transcription by disabling chromatin. Hes proteins also heterodimerize with bHLH repressors such as Hey1 and Hey2, a process which also blocks transcription. Hes factors also heterodimerize with bHLH activators such as E47, also known as Tcfe2a, and Mash1, also known as Ascl1, both of which are the mammalian homologs to proneural genes in Drosophila.
Allostery is the most direct and efficient way for regulation of biological macromolecule function induced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site. Due to the inherent high receptor selectivity and lower target-based toxicity, it is also expected to play a more positive role in drug discovery and bioengineering, leading to rapid growth on allosteric findings. Allosteric Database (ASD) provides a central resource for the display, search and analysis of the structure, function and related annotation for allosteric molecules. Currently, ASD contains allosteric proteins from more than 100 species and modulators in three categories (activators, inhibitors, and regulators).
About 60% of the world's production of hydrogen peroxide is used for pulp- and paper-bleaching. The second major industrial application is the manufacture of sodium percarbonate and sodium perborate, which are used as mild bleaches in laundry detergents. Sodium percarbonate, which is an adduct of sodium carbonate and hydrogen peroxide, is the active ingredient in such laundry products as OxiClean and Tide laundry detergent. When dissolved in water, it releases hydrogen peroxide and sodium carbonate, By themselves these bleaching agents are only effective at wash temperatures of or above and so, often are used in conjunction with bleach activators, which facilitate cleaning at lower temperatures.
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (IRF9), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus.
Concurrently with the mobilization of these pathways, activated DP2 also mobilizes G protein-coupled receptor kinases (GRKs, GRK2, GRK3, and/or GRK6) and Arrestin-2 (also termed Arrestin beta 1 or β-arrestin). The GRKs, along with the DAG-activated PKCs, phosphorylate DP2 to promote its internalization while arrestin-2 inhibits DP2 from further activating heterotrimeric G proteins while also linking DP2 to elements, clathrin and clathrin adaptor AP2, of the receptor internalization machinery. These pathways render DP2 unable to mobilize heterotrimereic G proteins thereby rendering the cell less sensitive or insensitive to further stimulation by DP ligands. The process, termed Homologous desensitization, serves as a physiological limiter of cell responses to DP2 activators.
In molecular biology there are a number of neurogenic proteins referred to as mastermind-like proteins (MAMLs) of which this domain is the N-terminal region. Mastermind-like proteins act as critical transcriptional co-activators for Notch signaling. The N-terminal domain of MAML proteins, MAML1, MAML2, MAML3, is a polypeptide of up to 70 residues, numbers 15-67 of which adopt an elongated kinked helix that wraps around ANK and CSL forming one of the complexes in the build-up of the Notch transcriptional complex for recruiting general transcription factors. This N-terminal domain is responsible for its interaction with the ankyrin repeat region of the Notch proteins NOTCH1, NOTCH2, NOTCH3 and NOTCH4.
The basis of the tire is formed by the carcass, normally a mixture of NR (natural rubber), SBR and BR. It should have a very good adhesion to the polyester cord, used as reinforcement. And the inner side of the tire is formed by the inner liner, normally consisting of halogenated butyl rubber (IIR) For all these compounds with their different properties different accelerators and mixtures of accelerators have to be used to obtain the required properties. A vulcanization accelerator is typically used in combination with sulfur as the cross-linker, and with zinc oxide and stearic acid as activators. Other additives can be added too, but for the cross- linking reaction, those mentioned above are the most important.
In addition to directly affecting chromatin structure, there are a number of ways in which SINEs can potentially regulate gene expression. For example, long non-coding RNA can directly interact with transcriptional repressors and activators, attenuating or modifying their function. This type of regulation can occur in different ways: the RNA transcript can directly bind to the transcription factor as a co-regulator; also, the RNA can regulate and modify the ability of co-regulators to associate with the transcription factor. For example, Evf-2, a certain long non-coding RNA, has been known to function as a co-activator for certain homeobox transcription factors which are critical to nervous system development and organization.
DOCK proteins are known activators of small G proteins of the Rho family. A study of Dock7 in HEK 293 cells and hippocampal neurons has shown that it can bind and promote nucleotide exchange on the Rac subfamily isoforms Rac1 and Rac3. This work suggests that Dock7 is a key mediator of the process that specifies which of the many neurites will become the axon. Indeed, overexpression of Dock7 induced the formation of multiple axons and RNA interference knock-down of Dock7 prevented axon formation. In Schwann cells Dock7 was shown to regulate the activation of Cdc42 as well as Rac1 however no direct interaction between Dock7 and Cdc42 has been demonstrated.
Some studies have suggested that mTOR signaling may increase during aging, at least in specific tissues like adipose tissue, and rapamycin may act in part by blocking this increase. An alternative theory is mTOR signaling is an example of antagonistic pleiotropy, and while high mTOR signaling is good during early life, it is maintained at an inappropriately high level in old age. Calorie restriction and methionine restriction may act in part by limiting levels of essential amino acids including leucine and methionine, which are potent activators of mTOR. The administration of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway in the hypothalamus.
The relatively high cost of conventional bleaching systems restrict their spread in emerging markets, where cold water is used for washing and photobleaching by sunlight is widespread, or the use of sodium hypochlorite solution is common (as in the US). There remains considerable potential in Europe for more active bleach activators due to the significant potential energy savings achievable by washing at lower temperatures, but their higher activity must not be accompanied by greater damage to textile dyes and fibers. In addition to stain bleaching in laundry, the disinfecting and deodorizing effects of bleach/activator combinations also play an important role. Therefore, they are also used in dishwashing detergents and denture cleaners.
The Pendolino features an actively actuated tilt system. Each of the carriages can tilt up to eight degrees from the horizontal; this is done for the purpose of better managing the forces imposed between high speed trains and the track while traversing corners. On top of this, the lines of the Network Rail network are often canted up to six degrees, akin to a shallow-banked cyclodrome; when combined with the Pendolino's tilt system, the train can reportedly comfortably take curves at a 20 per cent greater speed than it otherwise would be able to do so. The active tilting mechanism is achieved using electrically operated tilt activators, which are situated under each carriage.
The allosteric regulators of GLUD1 - ADP, GTP, Leu, NAD+ and NADH - exert their effects by changing the energy required to open and close the catalytic cleft during enzymic turnover, in other words by destabilizing or stabilizing, respectively, the abortive complexes. Activators are not necessary for the catalytic function of GLUD1, as it is active in the absence of these compounds (basal state). It has been suggested that GLUD1 assumes in its basal state a configuration (open catalytic cleft) that permits catalytic activity regardless of whether the allosteric sites are functional. GLUD regulation is of particular biological importance as exemplified by observations showing that regulatory mutations of GLUD1 are associated with clinical manifestations in children.
Of India. He served as a member of the Review Committee on Genetic Manipulation of the Department of Biotechnology, Ministry of Science and Technology, India; Science Panel member, the Department for International Development/ Biotechnology and Biological Sciences Research Council (DFID/BBSRC) of the UK Government, 2006-2007. He is currently a member of Board Of Governors, National Institute of Technology, Warangal, AP, India. His research interests are: capturing differentially expressed genes during drought stress, cloning and functional analysis of promoter regions of target genes of drought response; isolation and characterization of family of drought responsive transcriptional activators; study of processes and pathways that are common to drought, salt and submergence; expression profiling of stress responsive genes.
This +23 RUNX1 enhancer contains conserved motifs that encourage binding of various haematopoiesis related regulators such as Gata2, ETS factors (Fli-1, Elf-1, PU.1) and the SCL / Lmo2 / Ldb1 complex, as well as RUNX1 itself acting in an auto-regulatory loop. As mentioned before, the main role of RUNX1 is to modulate the fate of haematopoietic cells. This can be achieved by binding to the thrombopoietin (TPO) receptor/ c-Mpl promoter, followed by the recruitment of transcription activators or repressors in order to promote transition of the hemogenic endothelium to HSCs, or differentiation into lineages of lower haematopoietic hierarchies. RUNX1 can also modulate its own level by upregulating the expression of Smad6 to target itself for proteolysis.
A biomolecular target (most commonly a protein or a nucleic acid) is a key molecule involved in a particular metabolic or signaling pathway that is associated with a specific disease condition or pathology or to the infectivity or survival of a microbial pathogen. Potential drug targets are not necessarily disease causing but must by definition be disease modifying. In some cases, small molecules will be designed to enhance or inhibit the target function in the specific disease modifying pathway. Small molecules (for example receptor agonists, antagonists, inverse agonists, or modulators; enzyme activators or inhibitors; or ion channel openers or blockers) will be designed that are complementary to the binding site of target.
ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport.
The following standard prostaglandins have the following relative efficacies in binding to and activating EP2: PGE2>PGF2alpha>=PGI2>PGD2. The receptor binding affinity Dissociation constant Kd (i.e. ligand concentration needed to bind with 50% of available EP1 receptors) is ~13 nM for PGE2 and ~10 nM for PGE1 with the human receptor and ~12 nM for PGE2 with the mouse receptor. Because PGE2 activates multiple prostanoid receptors and has a short half-life in vivo due to its rapidly metabolism in cells by omega oxidation and beta oxidation, metabolically resistant EP2-selective activators are useful for the study of this receptor's function and could be clinically useful for the treatment of certain diseases.
The importance of PDGFRA during development is apparent from the observation that the majority of mice lacking a functional Pdgfra gene develop a plethora of embryonic defects, some of which are lethal; the mutant mice exhibit defects in kidney glomeruli because of a lack of mesangial cells but also suffer an ill-defined blood defect characterized by thrombocytopenic, a bleeding tendency, and severe anemia which could be due to blood loss. The mice die at or shortly before birth. PDGF-A and PDGF-C seem to be the important activators of PDGFRα during development because mice lacking functional genes for both these PDGFRA activating ligands, i.e. Pdgfa/Pdgfc- double null mice show similar defects to Pdgra null mice.
This finding was validated by multiple independent studies occurring shortly thereafter, and has since been observed in multiple animal models and human tissue, as well as in studies employing transgenesis and PKCε activators/inhibitors. Mitochondrial targets of PKCε involved in cardioprotection have been actively pursued, since the translocation of PKCε to mitochondria following protective stimuli is one of the most well-accepted cardioprotective paradigms. PKCε has been shown to target and phosphorylate alcohol dehydrogenase 2 (ALDH2) following preconditioning stimuli, which increased the activity of ALDH2 and reduced infarct size. Moreover, PKCε interacts with cytochrome c oxidase subunit IV (COIV), and preconditioning stimuli evoked phosphorylation of COIV and stabilization of COIV protein and activity.
The intronless gene for this transcription coactivator is located between the protocadherin beta and gamma gene clusters on chromosome 5. The protein encoded by this gene is a component of the TFIID protein complex, a complex which binds to the TATA box in class II promoters and recruits RNA polymerase II and other factors. This particular subunit interacts with the largest TFIID subunit, as well as multiple transcription activators. The protein is required for transcription by promoters targeted by RNA polymerase II. The general transcription factor, TFIID, consists of the TATA-binding protein (TBP) associated with a series of TBP-associated factors (TAFs) that together participate in the assembly of the transcription preinitiation complex.
Scheme. 1. i: N-Chlorosuccinimide; Bn = -CH2Ph In the early 1950s, Alexander Todd’s group pioneered H-phosphonate and phosphate triester methods of oligonucleotide synthesis. The reaction of compounds 1 and 2 to form H-phosphonate diester 3 is an H-phosphonate coupling in solution while that of compounds 4 and 5 to give 6 is a phosphotriester coupling (see phosphotriester synthesis below). Scheme 2. Synthesis of oligonucleotides by the H-Phosphonate Method Thirty years later, this work inspired, independently, two research groups to adopt the H-phosphonate chemistry to the solid-phase synthesis using nucleoside H-phosphonate monoesters 7 as building blocks and pivaloyl chloride, 2,4,6-triisopropylbenzenesulfonyl chloride (TPS-Cl), and other compounds as activators.
IL-33 is synthesized as a 31-kDa precursor form and binds the ST2 receptor and IL-1RAcP coreceptor, which stimulates signaling that activates transcription factors as NF-κB and ERK, p38 and JNK MAPKs. The signaling can be triggered by a precursor form of IL-33 in the same way as IL-1α precursor activates signaling through the IL-1 receptor. On the other hand, the mature forms IL-3395-270, IL-3399-270 and IL-33109-270, which are processed from a precursor by serine proteases cathepsin G and elastase, are even more potent activators of inflammatory responses. In contrast with IL-1, processing by caspases, like caspase-1, results in IL-33 inactivation.
DNA associates with histone proteins to form chromatin Kundu's researches are principally focused on the regulation of transcription and P53 function using chromatin and associated proteins as well as on the functional genomics of transcriptional co-activators. His researches assisted in the identification of PC4 and its role as a functional component of chromatin and as an activator of P53. He demonstrated the histone chaperone activity and the acetylation of chromatin transcription and these findings have been reported to have helped in identifying new drug candidates. Extending his researches to cancer and AIDS therapeutics, he has identified small molecule modulators of chromatin modifying enzymes, a discovery which is reported to be helpful in developing new therapeutic protocols.
Martelli won the 2002 Activators' Choice Award, and the 2006 Frank Willison award for outstanding contributions to the Python community. Before joining Google, Martelli spent a year designing chips with Texas Instruments; eight years with IBM Research, gradually shifting from hardware to software, and winning three Outstanding Technical Achievement Awards; 12 as Senior Software Consultant at think3, Inc., developing libraries, network protocols, GUI engines, event frameworks, and web access frontends; and three more as a freelance consultant, working mostly for Open End AB, a Python-centered software house (formerly known as Strakt AB) located in Gothenburg, Sweden. He has taught courses on programming, development methods, object-oriented design, cloud computing, and numerical computing, at Ferrara University and other schools.
Splicing repression Splicing is regulated by trans-acting proteins (repressors and activators) and corresponding cis-acting regulatory sites (silencers and enhancers) on the pre-mRNA. However, as part of the complexity of alternative splicing, it is noted that the effects of a splicing factor are frequently position-dependent. That is, a splicing factor that serves as a splicing activator when bound to an intronic enhancer element may serve as a repressor when bound to its splicing element in the context of an exon, and vice versa. The secondary structure of the pre-mRNA transcript also plays a role in regulating splicing, such as by bringing together splicing elements or by masking a sequence that would otherwise serve as a binding element for a splicing factor.
Klf4, also known as gut-enriched Krüppel-like factor (GKLF), acts as a transcriptional activator or repressor depending on the promoter context and/or cooperation with other transcription factors. For example, Klf4 transactivates the iNOS promoter in cooperation with p65 (RelA), and the p21Cip1/Waf1 promoter in cooperation with p53, but it directly suppresses the p53 promoter and inhibits ornithine decarboxylase (ODC) promoter activity by competing with specificity protein-1 (Sp-1). Klf4 also interacts with the p300/CBP transcription co-activators. Klf5, also known as intestinal enriched Krüppel-like factor (IKLF) or basic transcription element binding protein 2 (Bteb2), has been assigned purely transcriptional activation activity but, similar to Klf4, binds p300 which acetylates the first zinc finger conferring a trans-activating function.
481x481px Given the many studies on frustrated Lewis pairs (FLP) that point them towards high potential small molecule activators, Piers and coworkers set out to investigate whether the strong electrophilicity of antiaromatic boroles might entail a comparable reactivity. In a seminal paper published in 2010, they successfully demonstrated the metal-free activation of dihydrogen by [PhBC4Ph4] and its perfluorinated analog. Their studies initially focused on perfluorinated [PhBC4Ph4] due to its exceptionally high Lewis acid strength, which readily reacted with H2 both in solution and in the solid state to form two possible isomers as shown above. DFT calculations show that the trans product is thermodynamically favoured by 6.2 kcal mol−1, but no interconversion between isomers was observed under thermal conditions.
Capsaicin and RTX, elicit burning pain by activating a non-selective cation channel expressed on sensory nerve endings. When capsaicin was found to have analgesic effects in preclinical studies much emphasis was put into the research of the receptor/channel that capsaicin binds to and activates. Besides being activated by capsaicin, TRPV1 also responds to a wide range of exogenous and endogenous chemical ligands as well as physical stimuli such as heat over 42 °C and changes in more diverse activators such as protons (acid, pH<6). TRPV1 is also subject to regulation by changes in membrane potential and this intrinsic voltage-dependence is thought to underlie the gating mechanism of this non-selective cation channel which leads to the influx of sodium and calcium ions.
Excitation of rhodopsin in mammalian photoreceptors leads to the hyperpolarization of the receptor membrane but not to depolarization as in the insect eye. In Drosophila and, it is presumed, other insects, a phospholipase C (PLC)-mediated signaling cascade links photoexcitation of rhodopsin to the opening of the TRP/TRPL channels. Although numerous activators of these channels such as phosphatidylinositol-4,5-bisphosphate (PIP2) and polyunsaturated fatty acids (PUFAs) were known for years, a key factor mediating chemical coupling between PLC and TRP/TRPL channels remained a mystery until recently. It was found that breakdown of a lipid product of PLC cascade, diacylglycerol (DAG), by the enzyme diacylglycerol lipase, generates PUFAs that can activate TRP channels, thus initiating membrane depolarization in response to light.
There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system. FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients. As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they explain only certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.
STAT3 is a member of the STAT protein family. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), form homo- or heterodimers, and translocate to the cell nucleus where they act as transcription activators. Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons, epidermal growth factor (EGF), Interleukin (IL-)5 and IL-6. Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by Mitogen-activated protein kinases (MAPK) and through c-src non-receptor tyrosine kinase.. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis.
BABA applied as a foliar spray causes the plant hormone salicylic acid (SA) to accumulate, which is a key hormone in controlling systemic acquired resistance (SAR). Genetically modified tobacco plants that are unable to accumulate SA are still protected by BABA against some pathogens, but not others, indicating pathosystem-specific mechanisms by which BABA confers resistance. Arabidopsis unable to produce SA, jasmonic acid or ethylene (other hormones involved in defence) were still protected from the oomycete Peronospora parasitica but plants unable to produce SA were susceptible to the bacteria Pseudomonas syringae. This variation in the hormones required for BABA to confer resistance makes it differ from other synthetic activators of plant defence, which only operate through the SAR pathway of PR proteins.
In 1965 she moved to the University of Oxford to work with Edith Bülbring, being appointed as fellow and tutor in physiology at Lady Margaret Hall, Oxford in 1968, lecturer in pharmacology in 1972 and a professor in 1996. Her research focussed on the function of smooth muscle, particularly that which controls the contraction of the urinary bladder and urethra. Her early work focussed on the role of ions (particularly chloride) in the regulation of smooth muscle, developing new ways to measure the concentration of ions inside cells. In mid-career, she studied the function of drugs that relax smooth muscle, particularly potassium channel activators, moving on to develop important ties with Urological surgeons in Oxford to form the Oxford Continence Group.
Edwards has voted multiple times against Castle Doctrine bills. In January 2011, Edwards voted against Senate Bill 876 (Castle Doctrine) which would have allowed "a lawful occupant use of physical force, including deadly force, against an intruder in his dwelling who has committed an overt act against him, without civil liability." Norfolk Examiner, January 19, 2011 In February 2011, Edwards was one of eight senators on the Senate Courts of Justice Committee who "passed by indefinitely" House Bill 1573, defeating the bill by an 8 to 4 margin.National Rifle Association, February 15, 2011 In February 2020, Edwards broke party ranks to shelve House Bill 961 (gun control) which would have prohibited the sale and transport of assault firearms, certain firearm magazines, silencers, and trigger activators.
The transcriptional regulation of the genome is controlled primarily at the preinitiation stage by binding of the core transcriptional machinery proteins (namely, RNA polymerase, transcription factors, and activators and repressors) to the core promoter sequence on the coding region of the DNA. However, DNA is tightly packaged in the nucleus with the help of packaging proteins, chiefly histone proteins to form repeating units of nucleosomes which further bundle together to form condensed chromatin structure. Such condensed structure occludes many DNA regulatory regions, not allowing them to interact with transcriptional machinery proteins and regulate gene expression. To overcome this issue and allow dynamic access to condensed DNA, a process known as chromatin remodeling alters nucleosome architecture to expose or hide regions of DNA for transcriptional regulation.
In molecular biology, barrier-to-autointegration factor (BAF) is a family of essential proteins that is highly conserved in metazoan evolution, and which may act as DNA-bridging proteins. BAF binds directly to double-stranded DNA, to transcription activators, and to inner nuclear membrane proteins, including lamin A filaments that anchor nuclear pore complexes in place, and nuclear LEM-domain proteins that bind to laminin filaments and chromatin. New findings suggest that BAF has structural roles in nuclear assembly and chromatin organization, represses gene expression and might interlink chromatin structure, nuclear architecture and gene regulation in metazoans. BAF can be exploited by retroviruses to act as a host component of pre-integration complexes, which promote the integration of the retroviral DNA into the host chromosome by preventing autointegration (integration into itself).
Once recruited to origins, ORC and its co-factors Cdc6 and Cdt1 drive the deposition of the minichromosome maintenance 2-7 (Mcm2-7) complex onto DNA. Like the archaeal replicative helicase core, Mcm2-7 is loaded as a head-to-head double hexamer onto DNA to license origins. In S-phase, Dbf4-dependent kinase (DDK) and Cyclin-dependent kinase (CDK) phosphorylate several Mcm2-7 subunits and additional initiation factors to promote the recruitment of the helicase co-activators Cdc45 and GINS, DNA melting, and ultimately bidirectional replisome assembly at a subset of the licensed origins. In both yeast and metazoans, origins are free or depleted of nucleosomes, a property that is crucial for Mcm2-7 loading, indicating that chromatin state at origins regulates not only initiator recruitment but also helicase loading.
Although copper complexes (in combination with relevant ligands) have long been used as catalysts for organic reactions such as atom transfer radical addition (ATRA) and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC), copper complex catalyzed RDRP was not reported until 1995 when Jin-Shan Wang and Krzysztof Matyjaszewski introduced it as atom transfer radical polymerization (ATRP). ATRP with copper as catalyst quickly became one of the most robust and commonly used RDRP techniques for designing and synthesizing polymers with well-defined composition, functionalities, and architecture. Due to some inherited drawbacks, such the persistent radical effect (PRE), several advanced ATRP techniques have been developed, including activators regenerated by electron transfer (ARGET) ATRP and initiators for continuous activator regeneration (ICAR) ATRP. One intriguing catalyst, metallic copper, has also been applied to these modified ATRP systems.
Following tissue injury, the inflammatory response is a protective process to promote restoration of the tissue to homeostasis. Resolution of inflammation involves various specialized lipid mediators, including resolvins. Resolvins are under laboratory research for their potential to act through G protein-coupled receptors (GPRs): 1) RvD1 and AT- RvD1 act through the Formyl peptide receptor 2, which is also activated by certain lipoxins and is therefore often termed the ALX/FPR2 receptor; 2) RvD1, AT-RVD1, RvD3, AT-RvD3, and RvD5 act through the GPR32 receptor which is now also termed the RVD1 receptor; 3) RvD2 acts through the GPR18 receptor also now termed the RvD2 receptor; and 4) RvE1 and the 18(S) analog of RvE1 are full activators while RvE2 is a partial activator of the CMKLR1 receptor. All of these receptors activate their parent cells through standard GPR-mobilized pathways.
Most notably, 4 subunits of yeast APC/C consist almost entirely of multiple repeats of the 34 amino acid tetratricopeptide residue (TPR) motif. These TPR subunits, Cdc16, Cdc27, Cdc23, and Apc5, mainly provide scaffolding and support to mediate other protein-protein interactions. Cdc27 and Cdc23 have been shown to support the binding of Cdc20 and Cdh1, as mutations in key residues of these subunits led to increased dissociation of the activators. Apc10/Doc1, has been shown to promote substrate binding by mediating their interactions with Cdh1 and Cdc20. In particular, CDC20 (also known as p55CDC, Fizzy, or Slp1) inactivates CDK1 via ubiquitination of B-type cyclins. This results in activation of Cdh1(a.k.a. Fizzy-related, Hct1, Ste9, or Srw1), which interacts with APC during late mitosis and G1/G0. Cdh1 is inactivated via phosphorylation during S, G2 and early M phase.
In addition, the GDNA method provided a framework to study biological relay mechanisms in circadian networks through which modules communicate changes in gene expression. The authors observed signal propagation through interactions between activators and repressors, and uncovered unidirectional paralog compensation among several clock gene repressors—for example, when PER1 is depleted, there is an increase in Rev- erbs, which in turn propagates a signal to decrease expression in BMAL1, the target of the Rev-erb repressors. By examining knockdown of several transcriptional repressors, GDNA also revealed paralog compensation where gene paralogs were upregulated through an active mechanism by which gene function is replaced following knockdown in a nonredunant manner—that is, one component is sufficient to sustain function. These results further suggested that a clock network utilizes active compensatory mechanisms rather than simple redundancy to confer robustness and maintain function.
The antimony-V acted as the primary activator and produced a broad blue emission. Addition of manganese-II produced a second broad peak to appear at the red end of the emission spectrum at the expense of the antimony peak, excitation energy being transferred from the antimony to the manganese by a non radiative process and making the emitted light appear less blue and more pink. Replacement of some of the fluoride ions with chloride ions in the lattice caused a general shift of the emission bands to the longer wavelength red end of the spectrum. These alterations allowed phosphors for Warm White, White and Daylight tubes, (with corrected color temperatures of 2900, 4100 and 6500 K respectively), to be made. The amounts of the manganese and antimony activators vary between 0.05 and 0.5 mole percent.
Cell culture example of a small molecule as a tool instead of a protein. In cell culture to obtain a pancreatic lineage from mesodermal stem cells, the retinoic acid signaling pathway must be activated while the sonic hedgehog pathway inhibited, which can be done by adding to the media anti-shh antibodies, Hedgehog interacting protein, or cyclopamine, where the first two molecules are proteins and the last a small molecule. Enzymes and receptors are often activated or inhibited by endogenous protein, but can be also inhibited by endogenous or exogenous small molecule inhibitors or activators, which can bind to the active site or on the allosteric site. An example is the teratogen and carcinogen phorbol 12-myristate 13-acetate, which is a plant terpene that activates protein kinase C, which promotes cancer, making it a useful investigative tool.
KvLQT1 has been shown to interact with PRKACA, PPP1CA and AKAP9. KvLQT1 can also associate with any of the five members of the KCNE family of proteins, but interactions with KCNE1, KCNE2, KCNE3 are the only interactions within this protein family that affect the human heart. KCNE2, KCNE4, and KCNE5 have been shown to have an inhibitory effect on the functionality of KvLQT1, while KCNE1 and KCNE3 are activators of KvLQT1. KvLQT1 can associate with KCNE1 and KCNE4 with the activation effects of KCNE1 overriding the inhibitory effects of KCNE4 on the KvLQT1 channel, and KvLQT1 will commonly associate with anywhere from two to four different KCNE proteins in order to be functional. However, KvLQT1 most commonly associates with KCNE1 and forms the KvLQT1/KCNE1 complex since it has only been seen to function in vivo when associated with another protein.
These metabolites proceed to act directly or indirectly to recruit circulating leukocytes, tissue macrophages, and tissue dendritic cells to the disturbed tissue site. The consequential congregation of the various cell types promotes transcellular pathways in forming specialized pro-resolving mediators (SPMs), including the LXs, which then proceed to stimulate cellular and tissue responses that trend to reverse the actions of the pro-inflammatory mediators, dampen and reverse the inflammatory response, and initiate tissue repair. LXA4 and 15-epi-LXA4 are high affinity receptor ligands for and activators of the FPR2 receptor. FPR2, which is now termed the ALX, ALX/FPR, or ALX/FPR2 receptor, is a G protein coupled receptor initially identified as a receptor for the leukocyte chemotactic factor, N-Formylmethionine-leucyl-phenylalanine (FMLP), based on its amino acid sequence similarity to the known FMLP receptor, FPR1.
13(S)-HpODE, and 13(S)-HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in Chinese hamster ovary cells made to express these receptors; they are, however, far weaker GPR132 activators than 9(S)-HpODE or 9(S)-HODE. GPR132 was initially described as a pH sensing receptor; the role(s) of 13(S)-HpODE and 13(S)-HODE as well as 9(S)-HpODE, 9(S)HODE, and a series or GPR132-activating arachidonic acid hydroxy metabolites (i.e. HETEs) in activating G2A under the physiological and pathological conditions in which G2A is implicated (see GPR132 for a lists of these conditions) have not yet been determined. This determination, as it might apply to humans, is made difficult by the inability of these HODEs to activate rodent GPR132 and therefore to be analyzed in rodent models.
AMOT, AMOTL1 and AMOTL2 play critical roles in the Hippo signaling pathway by regulating the subcellular localization of the co-activators YAP (Yes- associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif), and activating LATS2 through a novel conserved domain. The activity of YAP and TAZ can be restricted through their interaction with AMOT and AMOTL1, and such interaction depends on the WW domain of TAZ and the Proline- Proline-x–Tyrosine motif at the N-terminus of AMOT. In position-dependent Hippo signaling, where the outer and inner cells are polar and nonpolar respectively, AMOT and AMOTL2 are essential for Hippo pathway activation and appropriate cell fate specification. In the nonpolar inner cells, AMOT localizes to adherens junctions (AJs), and Ser-176 at the N-terminal domain is phosphorylated by LATS downstream of GPCR signaling, which inhibits actin binding activity and stabilizes the AMOT-LATS interaction to activate the Hippo pathway.
For some animal tissues, such as mammalian skin, it is clear that the growth of the skin is ultimately determined by the size of the body whose surface area the skin covers. This suggests that cell proliferation in skin stem cells within the basal layer is likely to be mechanically controlled to ensure that the skin covers the surface of the entire body. Growth of the body causes mechanical stretching of the skin, which is sensed by skin stem cells within the basal layer and consequently leads to both an increased rate of cell proliferation as well as promoting the planar orientation of stem cell divisions to produce new skin stem cells, rather than only producing differentiating supra-basal daughter cells. Cell proliferation in skin stem cells within the basal layer can be driven by the mechanically-regulated YAP/TAZ family of transcriptional co-activators, which bind to TEAD-family DNA binding transcription factors in the nucleus to activate target gene expression and thereby drive cell proliferation.
It has been demonstrated that TFIIH is a rate-limiting factor for HIV transcription in unactivated T-cells by using a combination of in vivo ChIP experiments and cell-free transcription studies.Kim YK et al., Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. EMBO J. 2006 Aug 9;25(15):3596-604 The ability of NF-κB to rapidly recruit TFIIH during HIV activation in T-cells is an unexpected discovery; however, there are several precedents in the literature of cellular genes that are activated through the recruitment of TFIIH. In an early and influential paper,Blau J , Xiao H , McCracken S , O'Hare P , Greenblatt J , Bentley D (1996) Three functional classes of transcriptional activation domains. Mol Cell Biol 16: 2044–2055 demonstrated that type I activators such as Sp1 and CTF, which were able to support initiation but were unable to support efficient elongation, were also unable to bind TFIIH.
Telethonin KO animals also displayed calcium transient dysynchrony, T-tubule loss and depressed L-type calcium channel function. Telethonin is a substrate of titin kinase, protein kinase D (PKD) and CaM Kinase II. Telethonin, as well as TNNI3, MYBPC3 and MYOM2 are phosphorylated by PKD in cardiomyocytes, and this leads to a reduction in calcium sensitivity of myofilaments, as well as accelerated crossbridge kinetics. Bis-phosphorylation of Telethonin specifically at sites Serine-157 and Serine-161 has been shown to be essential for normal T-tubule organization and intracellular calcium transient kinetics. The intracellular degradation of Telethonin is regulated by MDM2 in a proteasomal-dependent yet ubiquitin-independent manner.. Telethonin specifically interacts with the pro-apoptotic protein Siva, suggesting that Telethonin may be involved in the mechanism underlying Coxsackievirus B3 infection in acute and chronic myocarditis Telethonin was also identified to be targeted and regulated by transcriptional activators CLOCK and BMAL1, thus demonstrating that TCAP is a circadian regulated gene.
CyclinB- Cdk1 Hysteresis Graph The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at different checkpoints of the cell cycle. Different phases of the cell cycle experience activation and/or deactivation of specific cyclin-CDK complexes. CyclinB-CDK1 activity is specific to the G2/M checkpoint. Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to enter mitosis. Cdc2 activity is further regulated by phosphorylation/dephosphorylation of its corresponding activators and inhibitors. Through a positive feedback loop, CyclinB-Cdc2 activates the phosphatase Cdc25 which in turn deactivates the CyclinB-Cdc2 inhibitors, Wee1 and Myt1. Cdc25 activates the complex through the removal of phosphates from the active site while Wee1 inactivates the complex through the phosphorylation of tyrosine residues, specifically tyrosine-15. This loop is further amplified indirectly through the coordinated interaction of the Aurora A kinase and the Bora cofactor.
These studies show that the deleterious effects of prior hyperglycemic exposure have long-lasting effects on target organs even after subsequent glycaemic control underscoring the beneficial effects of intensive glycemic control in diabetes. The persistence of these symptoms points to epigenesis as an underlying cause. Studies have shown that the islet dysfunction and development of diabetes in rats is associated with epigenetic silencing via DNA methylation of the gene Pdx1 promoter, which produces a key transcription factor that regulates beta-cell differentiation and insulin gene expression. Silencing at this promoter decreases the amount of beta-cells produced which leads to insulin resistance and the inability of the beta-cells to produce an important peptide that prevents vascular deterioration and neuropathy caused from vascular inflammatory responses. A subsequent study shows that under high glucose conditions, islet-specific transcription factor Pdx1 was shown to stimulate insulin expression by recruiting co-activators p300 and the Histone methyl transferase SETD7/9, which increased histone acetylation and H3K4me2, respectively, and the formation of open chromatin at the insulin promoter.
TRPA1 can be considered to be one of the most promiscuous TRP ion channels, as it seems to be activated by a large number of noxious chemicals found in many plants, food, cosmetics and pollutants. Activation of the TRPA1 ion channel by the olive oil phenolic compound oleocanthal appears to be responsible for the pungent or "peppery" sensation in the back of the throat caused by olive oil. Although several nonelectrophilic agents such as thymol and menthol have been reported as TRPA1 agonists, most of the known activators are electrophilic chemicals that have been shown to activate the TRPA1 receptor via the formation of a reversible covalent bond with cysteine residues present in the ion channel. For a broad range of electrophilic agents, chemical reactivity in combination with a lipophilicity enabling membrane permeation is crucial to TRPA1 agonistic effect. A dibenz[b,f][1,4]oxazepine derivative substituted by a carboxylic methylester at position 10 has been reported to be a potent TRPA1 agonist (EC50 = 0.13μM or pEC50 = 6.90).
Exceedingly small amounts of tomato systemin are active, femto-molar concentrations of the peptide are sufficient to elicit a response at the whole plant level, making it one of the most potent gene activators identified. A receptor for tomato systemin was identified as a 160KDa leucine-rich repeat receptor like kinase (LRR-RLK), SR160. After being isolated it was found that was very similar in structure to BRI1 from A. thaliana, the receptor that brassinolides bind to on the cell membrane. This was the first receptor which was found to be able to bind both a steroid and a peptide ligand and also to be involved in both defensive and developmental responses. Recent studies have found that the initial conclusion that BRI1 is the receptor for tomato systemin may be incorrect. In cu3 mutants of tomato, a null allele with a stop codon present in the extracellular LRR domain of BRI1 prevents the receptor from being localised correctly and it also lacks the kinase domain, required for signalling.
Relationships between creative capitals, creative city and urban smartness With the very important book Reimagining Urbanism (Trento, ListLab, 2014) he has investigated and interpreted the challenges of western cities - and Sicilian one - in the age of never-ending metamorphosis not only as a powerful attractor of population, but also as a responsible subject of a new relationship with the suburban and rural areas, as activators of beautiful creative eco-systems based on new digital/physical citymakers. The book proposes an urbanism capable of producing resources for a new urban metabolism that can be reconciled with environmental protection, with the reduction of consumption, with the consolidation of the welfare state, food creation, as well as the promotion of innovative startups can stimulate the intelligence and creativity, to extend urban agriculture and recycling, to manage energy adaptation and climate efficiency of the city of the futureSee the Institute for Advanced Architecture of Catalonia 2014 Spring Lectures. With the new book Augmented City. A Paradigm Shift (Trento-Barcelona, ListLab, 2017) he proposes a new paradigm for more sensible, open source, intelligent, creative and resilient cities, based on recycle for being more productive, fluid and reticular.
Other TRPA1 channel activators include JT-010 and ASP-7663, while channel blockers include A-967079, HC-030031 and AM-0902. The eicosanoids formed in the ALOX12 (i.e. arachidonate-12-lipoxygnease) pathway of arachidonic acid metabolism, 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (i.e. 12S-HpETE; see 12-Hydroxyeicosatetraenoic acid) and the hepoxilins (Hx), HxA3 (i.e. 8R/S-hydroxy-11,12-oxido-5Z,9E,14Z-eicosatrienoic acid) and HxB3 (i.e. 10R/S-hydroxy-11,12-oxido-5Z,8Z,14Z-eicosatrienoic acid) (see Hepoxilin#Pain perception) directly activate TRPA1 and thereby contribute to the hyperalgesia and tactile allodynia responses of mice to skin inflammation. In this animal model of pain perception, the hepoxilins are released in the spinal cord directly activate TRPA (and also TRPV1) receptors to augment the perception of pain. 12S-HpETE, which is the direct precursor to HxA3 and HxB3 in the ALOX12 pathway, may act only after being converted to these hepoxilins. The epoxide, 4,5-epoxy-8Z,11Z,14Z-eicosatrienoic acid (4,5-EET) made by the metabolism of arachidonic acid by any one of several cytochrome P450 enzymes (see Epoxyeicosatrienoic acid) likewise directly activates TRPA1 to amplify pain perception.
A number of newly occurring and fast spreading invasive insect pests and diseases such as Polyphagous Shot Hole Borer (PSHB) Euwallacea , which can vector plant pathogenic fungus Fusarium euwallaceae, and Sudden Oak Death (SOD) caused by an Oomycete Phytophthora ramorum, establish the use of trunk injection as the most efficient tree protection technique in landscapes and urban forestry. In the past and recently, trunk injection of pesticides and plant resistance activators has been investigated in agriculture for control of pathogens and insect pests on fruit tree crops and grapevines. The most investigated are diseases and pests of avocado, apple, and grapevine, such as Phytophthora root rot of avocado Phytophthora cinnamomi and avocado thrips Scirtothrips perseae, fire blight Erwinia amylovora and apple scab Venturia inaequalis, oblique banded leaf roller Choristoneura rosaceana and codling moth Cydia pomonella, and grapevine downy mildew Plasmopara viticola and powdery mildew Uncinula necator. Apple trees are especially interesting as a research model in agriculture since it is known that apple production requires intensive spray schedules for control of pathogenic fungus V. inaequalis with as many as 15-22 sprays of fungicides per season in humid climate.

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