The crucial molecule in the system that matches cell physiology to oxygen availability is a protein complex called hypoxia-inducible factor (HIF).
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The rest of us, he says, normally recover within a few months, so there's nothing to do but avoid triggers that bring on inducible headaches.
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Throughout the 1990s and 2000s, Kaelin, Ratcliffe, and Semenza worked separately to decode the actions of an oxygen-sensitive protein called HIF, for hypoxia inducible factor.
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Such biochemical arrangements almost always rely on feedback loops—and the crucial molecule in the loop that matches cell physiology to oxygen availability is a protein complex called hypoxia-inducible factor (HIF).
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Roxadustat is the first of a new kind of oral anaemia treatment called a hypoxia-inducible factor prolyl hydroxylase inhibitor that boosts production of red blood cells by mimicking the body's response to high altitude.
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Luke Dow completed his undergraduate and graduate work in Melbourne, Australia, before joining the laboratory of Scott Lowe in New York where he developed new approaches to interrogate gene function, specifically, the in vivo application of inducible shRNA and CRISPR-based genome editing tools.
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"About one in five adults with chronic hives are likely to have a physical or inducible-type hives that may be triggered by heat (warming of body temperature) as well as cold, and much less common, sunlight," Dr. Clifford Bassett, an allergist and founder of the Allergy & Asthma Care of New York, told Fox News.
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Hypoxia-inducible factor-asparagine dioxygenase (, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction : hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 \rightleftharpoons hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 Hypoxia-inducible factor- asparagine dioxygenase contains iron, and requires ascorbate.
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Hypoxia-inducible factor-proline dioxygenase (, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction : hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 \rightleftharpoons hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 Hypoxia-inducible factor-proline dioxygenase contains iron, and requires ascorbate. In humans, there are three isoforms of hypoxia- inducible factor-proline dioxygenase. These are PHD1, PHD2 and PHD3.
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Gamma-interferon-inducible protein Ifi-16 (Ifi-16) also known as interferon- inducible myeloid differentiation transcriptional activator is a protein that in humans is encoded by the IFI16 gene.
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Formate dehydrogenase-N (, Fdh-N, FdnGHI, nitrate-inducible formate dehydrogenase, formate dehydrogenase N, FDH-N, nitrate inducible Fdn, nitrate inducible formate dehydrogenase) is an enzyme with systematic name formate:quinone oxidoreductase. This enzyme catalyses the following chemical reaction : formate + quinone \rightleftharpoons CO2 \+ quinol This enzyme contains molybdopterin-guanine dinucleotides, five [4Fe-4S] clusters and two heme b groups.
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RPS3A has been shown to interact with DNA damage-inducible transcript 3.
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Lactose binds to the repressor protein and prevents it from repressing gene transcription. This is an example of the derepressible (from above: negative inducible) model.So it is a negative inducible operon induced by presence of lactose or allolactose.
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A. August, A. Sadra, B. Dupont and H. Hanafusa. “Src induced activation of Inducible T cell Kinase (ITK) requires PI3 kinase activity and the Pleckstrin Homology domain of inducible T cell kinase.” (1997) Proc. Natl. Acad. Sci. 94: 11227.
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This suggests evolutionary and inducible adaptations to allow consumption of certain host plants.
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It is constitutively expressed on mast cells and basophils and is inducible in eosinophils.
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BMP-2-inducible protein kinase is an enzyme in humans encoded by the BMP2K gene.
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Kaldenhoff was one of the first scientists to describe plant aquaporins.Kaldenhoff, R., A. Kolling, and G. Richter, A Novel Blue Light-Inducible and Abscisic Acid-Inducible Gene of Arabidopsis-Thaliana Encoding An Intrinsic Membrane-Protein. Plant Molecular Biology, 1993. 23(6): p. 1187-1198.
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Retinoid-inducible serine carboxypeptidase is an enzyme that in humans is encoded by the SCPEP1 gene.
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JunD has been shown to interact with ATF3, MEN1, DNA damage-inducible transcript 3 and BRCA1.
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Many resurrection plants use constitutive and inducible mechanisms to deal with drought and then later desiccation stress. Protective proteins such as cyclophilins, dehydrins, and LEA proteins are maintained at levels within a desiccation resistant species typically only seen during drought stress for desiccation sensitive species, providing a greater protective buffer as inducible mechanisms are activated. Some species also continuously produce anthocyanins and other polyphenols. An increase in the hormone ABA is typically associated with activation of inducible metabolic pathways.
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The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component.
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Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.
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Interferon alpha-inducible protein 27 is a protein that in humans is encoded by the IFI27 gene.
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Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ICOS gene. CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular.
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Cold-inducible RNA-binding protein is a protein that in humans is encoded by the CIRBP gene. The cold inducible RNA-binding protein CIRBP plays a critical role in controlling the cellular response upon confronting a variety of cellular stresses, including short wavelength ultraviolet light, hypoxia, and hypothermia.
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Asparagine can be hydroxylated in the HIF1 hypoxia inducible transcription factor. This modification inhibits HIF1-mediated gene activation.
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TGF beta-inducible nuclear protein 1 is a protein that in humans is encoded by the NSA2 gene.
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GDNF-inducible zinc finger protein 1 is a protein in humans that is encoded by the GZF1 gene.
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TCDD-inducible poly [ADP-ribose] polymerase is an enzyme that in humans is encoded by the TIPARP gene.
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Tumor protein p53-inducible protein 11 is a protein that in humans is encoded by the TP53I11 gene.
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Nitric oxide synthase, inducible is an enzyme which is encoded by the NOS2 gene in humans and mice.
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RB1-inducible coiled-coil protein 1 is a protein that in humans is encoded by the RB1CC1 gene.
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Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene.
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HIG1 hypoxia inducible domain family member 1B is a protein that in humans is encoded by the HIGD1B gene.
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BMP/retinoic acid inducible neural specific 3 is a protein that in humans is encoded by the BRINP3 gene.
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DNA-damage inducible 1 homolog 1 (S. cerevisiae) is a protein. In humans it is encoded by the DDI1 gene.
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Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia.
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When referring to a promoter some authors actually mean promoter + operator; i.e., the lac promoter is IPTG inducible, meaning that besides the lac promoter, the lac operator is also present. If the lac operator were not present the IPTG would not have an inducible effect.Lac operon Another example is the Tac-Promoter system (Ptac).
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Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHIs) also known as Hypoxia-Inducible Factor stabilizers (HIF stabilizers) are members of a class of new drugs that act by inhibiting prolyl hydroxylase which is responsible to break down the hypoxia-inducible factor (HIF) under normoxic conditions. they are being investigated for treatment of anemia, chronic kidney disease, cancer, and for their effects on heart tissue and others. Research conducted in mice suggests that they may increase hippocampal memory by increasing erythropoietin expression. They act by inhibiting HIF prolyl- hydroxylase enzymes.
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Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.
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Most terminal oxidases and reductases are inducible. They are synthesized by the organism as needed, in response to specific environmental conditions.
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Main article: AIM2 AIM2 is an acronym for absent in melanoma 2, and is sometimes also referred to as Interferon-inducible protein.
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In an inactive, UV-inducible photo-form they are harmless to bacteria cells, but are bactericidal after the activation with visible (amber) light.
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They are heat-inducible however, at 43 °C, they are not as effective as GrpE at protecting the cell from unfolded protein accumulation.
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Hypoxia-inducible factor (HIF)-1α has also been found to interact with hNaa10 to inhibit hNaa10-mediated activation of β-catenin transcriptional activity.
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Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.
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WNT1-inducible-signaling pathway protein 3 (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the WISP3 gene.
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Echinomycin is a peptide antibiotic. It intercalates into DNA at two specific sites, thereby blocking the binding of hypoxia inducible factor 1 alpha (HIF1alpha).
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Techniques include viral gene delivery, inducible gene expression, RNA-guided genome editing, and site-specific recombinases for applications related to biotechnology and cellular immunotherapy.
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Hypoxia inducible lipid droplet-associated (Hilpda, also known as C7orf68 and HIG-2) is a protein that in humans is encoded by the HILPDA gene.
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WNT1-inducible-signaling pathway protein 1 (WISP-1), also known as CCN4, is a matricellular protein that in humans is encoded by the WISP1 gene.
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WNT1-inducible-signaling pathway protein 2, or WISP-2 (also named CCN5) is a matricellular protein that in humans is encoded by the WISP2 gene.
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He created the classic induction of a lysogen, which involved irradiating the infected cells with ultraviolet light. He demonstrated through his classical experiments the inducible nature of the DNA repair system. The induction of DNA damage-response genes in bacteria has come to be known as the SOS response. This response includes DNA damage inducible mutagenesisWeigle JJ. Induction of Mutations in a Bacterial Virus.
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The gene is located on the short arm of the Crick strand of chromosome 11 (11p15.5). It is located with a cluster of interferon inducible genes but is itself not interferon inducible. The gene is 1,327 bases in length and encodes a protein of 132 amino acids with a predicted molecular weight of 14378 Daltons. Expression in adults is bone specific and highest in osteoblasts.
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Interferon (IFN)-inducible GTPases encompass four families of proteins including myxovirus resistant proteins (Mx), guanylate-binding proteins (GBP), immunity-related GTPase proteins (IRGs), and very large inducible GTPase proteins (VLIG). IRGs confer resistance from vacuolar pathogens by localizing to and disrupting the phagocytic vacuole during infection. The activation of IRGs in mice is induced by interferon. IRG genes have been identified in various vertebrates and some invertebrates.
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Sometimes modulation of transgene expression may be necessary since strong constitutive expression of a therapeutic gene in retinal tissues could be deleterious for long-term retinal function. Different methods have been utilized for the expression modulation. One way is using exogenously regulatable promoter system in AAV vectors. For example, the tetracycline- inducible expression system uses a silencer/transactivator AAV2 vector and a separate inducible doxycycline-responsive coinjection.
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Despite sharing similar amino acid sequence, Hsp90A expression is regulated in a different manner than Hsp90B. Hsp90A is the stress inducible isoform while Hsp90B is expressed constitutively. Several heat shock elements (HSE) are located upstream of Hsp90A allowing for its inducible expression. RNA levels measured in cell lines collected from cancer patients as well as normal tissue can be found at The Human Protein Atlas.
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Protein kinase, interferon-inducible double stranded RNA dependent activator, also known as interferon-inducible double stranded RNA-dependent protein kinase activator A or _P_ rotein _ACT_ ivator of the interferon-induced protein kinase (PACT) is a protein that in humans is encoded by the PRKRA gene. PACT heterodimerizes with and activates protein kinase R. PRKRA mutations have been linked to a rare form of dystonia parkinsonism.
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Hypoxemia, which is worsened by venous stasis, activates pathways—ones that include hypoxia-inducible factor-1 and early-growth-response protein 1. Hypoxemia also results in the production of reactive oxygen species, which can activate these pathways, as well as nuclear factor-κB, which regulates hypoxia-inducible factor-1 transcription. Hypoxia-inducible factor-1 and early-growth-response protein 1 contribute to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filled microvesicles, which presumably begin clotting after binding to the endothelial surface. D-dimers are a fibrin degradation product, a natural byproduct of fibrinolysis that is typically found in the blood.
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Nitric oxide synthase is expressed in epithelial cells of the liver, lung and bone marrow. It is inducible by a combination of lipopolysaccharide and certain cytokines.
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Activated Stat1 translocates to the nucleus and, after binding to a specific sequence in the promoter region of immediate- early IFN-γ-inducible genes, effects gene transcription.
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"Inducible defences as key adaptations for the successful invasion of Daphnia lumholtzi in North America?." Proceedings of the Royal Society B: Biological Sciences 276.1663 (2009): 1865-1873.
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IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes. Constitutive expression of IRF7 is largely restricted to lymphoid tissue, largely plasmacytoid dendritic cells, whereas IRF7 is inducible in many tissues.
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The three major pigments involved in floral color change are anthocyanins, carotenoids, and betalains. Color changes can occur from any of the following; an accumulation or loss of anthocyanins, accumulation or loss of carotenoids, or an accumulation of betalains. Floral color change may also be caused by an increase or decrease in pH causing a reddening/blueing of anthocyanins and co- pigments. Floral color change can be inducible or non-inducible.
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This means that the modification can be performed in an inducible and reversible manner, which reduces long-term secondary effects that would be caused by constitutive epigenetic modification.
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Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the EGLN1 gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate- dependent hydroxylase, a superfamily non-haem iron-containing proteins. In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase.
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Gloverin is an inducible antibacterial insect protein which inhibits the synthesis of vital outer membrane proteins leading to a permeable outer membrane. Gloverin contains a large number of glycine residues.
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The isoform, G6PDH, is regulated by transcription and posttranscription factors. Moreover, G6PD is one of a number of glycolytic enzymes activated by the transcription factor hypoxia-inducible factor 1 (HIF1).
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Myocilin, trabecular meshwork inducible glucocorticoid response, also known as MYOC, is a protein which in humans is encoded by the MYOC gene. Mutations in MYOC are a major cause of glaucoma.
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These cells produce large amounts of TGF beta and other suppressive cytokines, including IL-10, to prevent damage to the eye by reducing inflammation and causing T cells to differentiate to inducible T reg cells. Innate immune stimulation by bacteria and cellular stress is normally suppressed by myeloid suppression while inducible Treg cells prevent activation and clonal expansion of the autoreactive Th1 and Th17 cells that possess potential to cause damage to the eye. Whether through infection or other causes, this balance can be upset and autoreactive T cells allowed to proliferate and migrate to the eye. Upon entry to the eye, these cells may be returned to an inducible Treg state by the presence of IL-10 and TGF-beta from microglia.
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Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia- inducible factor-2alpha (HIF-2alpha)) is a protein that is encoded by the EPAS1 gene in humans. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart.
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Proc Natl Acad Sci U S A. 1953 Jul;39(7):628-36. (now referred to as Weigle mutagenesis in his honor) and inducible DNA repair following DNA damage (termed Weigle reactivation).
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Chemokine (C-C motif) ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.
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Mutated Ras also enhances glycolysis, partly through increasing the activity of Myc and hypoxia-inducible factors. Although HIF-1 inhibits Myc, HIF-2 activates Myc causing the multiplicity of the tumor cells.
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This overexpression promoted lipopolysaccharide (LPS)-inducible expression of HDAC- dependent genes via a HIF-1alpha-dependent mechanism. This demonstrated that HDAC7 may be a viable target for developing new anti-inflammatory drugs.
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DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene.
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It is commonly found in various soil and dung samples. C. subspirale produces the mycotoxin, oxaspirodion, which inhibits inducible TNF-a expression and inhibits the activation of the transcription factor NF-kappaB.
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It also functions in the ubiquitination of the tumor- suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases.
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Cytokine-inducible kinase is a putative serine/threonine kinase. CNK contains both a catalytic domain and a putative regulatory domain. It may play a role in regulation of cell cycle progression and tumorigenesis.
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SAA1 and SAA2 are highly inducible and hence called acute-phase SAA. Inflammatory cytokines such as IL-1β, IL-6 and TNF-α are major stimulants for hepatocyte expression of the SAA1 gene. Inducible expression of the acute-phase SAA genes is mainly regulated at the transcription level and involves the transcription factors C/EBP, NF-κB, AP2, SAF, Sp1 and STAT3. Elevation of the transcript of SAA1 is often seen in cDNA arrays used for detection of proinflammatory cytokine expression.
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There is a genetic element in individual susceptibility to cellulite. Researchers have traced the genetic component of cellulite to particular polymorphisms in the angiotensin converting enzyme (ACE) and hypoxia-inducible factor 1A (HIF1a) genes.
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These proteins are distantly related to the ionotropic glutamate-binding protein of the N-methyl D-aspartate (NMDA) receptor of man. Homologues include a putative cold shock inducible protein and a SecY stabilizing protein.
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Vousden's group have recently discovered a novel p53-regulated protein, TIGAR (T-p53 Inducible Glycolysis and Apoptosis Regulator), which can reduce oxidative stress in cells and might mediate part of this effect of p53.
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Mice also have 4 Saa genes. A major difference between human and mouse SAA genes is the expression of the mouse Saa3 gene for a functional protein, generally considered an inducible SAA in inflammatory tissues.
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Signaling through the PI3K-Akt pathway increases translation of hypoxia-inducible factor α (HIF1α and HIF2α) transcription factors via mTOR. HIF promotes gene expression of VEGF and glycolytic enzymes, allowing metabolism in oxygen-depleted environments.
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Virology, 1968. 36(1): p. 87-103. Hence, P2 has been regarded as the prototype for the non-inducible class of temperate phages. The mechanism about how P2 solve the induction-excision paradox still remains unknown.
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Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein that in humans is encoded by the TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) gene.
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Inducible synthesis of Mitomycin C resistance gene product (MCRA) from Streptomyces lavendulae. Gene: An International Journal on Genes and Genomes. 175:261-267. The second locus (mrd) binds with MC as a complex which prevents drug activation.
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Inducible expression systems such as theoriboswitches and pentatricopeptide repeat proteins have been widely studied in an effort to control and modulate expression of transgene products in transplastomic plants. One big advantage in using inducible expression systems is to optimize concentration of transgene protein production. For example, young plants need to devote energy and resources into growth and development to become mature plants. Constitutive expression of the transgene would therefore be detrimental for plant growth and development, as it takes away valuable energy and resources to express the foreign gene construct instead.
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An adaptive enzyme or inducible enzyme is an enzyme that is expressed only under conditions in which it is clearly of adaptive value, as opposed to a constitutive enzyme which is produced all the time. The Inducible enzyme is used for the breaking-down of things in the cell. It is also a part of the Operon Model, which illustrates a way for genes to turn "on" and "off". The Inducer causes the gene to turn on (controlled by the amount of reactant which turns the gene on).
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Nickel was voted Allergen of the Year in 2008 by the American Contact Dermatitis Society. In August 2015, the American Academy of Dermatology adopted a position statement on the safety of nickel: "Estimates suggest that contact dermatitis, which includes nickel sensitization, accounts for approximately $1.918 billion and affects nearly 72.29 million people."Position Statement on Nickel Sensitivity . American Academy of Dermatology(August 22, 2015) Reports show that both the nickel-induced activation of hypoxia-inducible factor (HIF-1) and the up-regulation of hypoxia-inducible genes are caused by depletion of intracellular ascorbate.
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Three isoforms are known for the NOS enzyme: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) - each with separate functions. The neuronal enzyme (NOS-1) and the endothelial isoform (NOS-3) are calcium-dependent and produce low levels of this gas as a cell signaling molecule. The inducible isoform (NOS-2) is calcium-independent and produces large amounts of gas that can be cytotoxic. NOS oxidizes the guanidine group of L-arginine in a process that consumes five electrons and results in the formation of NO with stoichiometric formation of L-citrulline.
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LIGHT stands for "homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes". In the cluster of differentiation terminology it is classified as CD258.
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As of 2010, current research indicates DLC1 negatively regulates angiogenesis in a paracrine fashion. This is by upregulation of VEGF mediated through the epidermal growth factor receptor (EGFR)-MAP/ERK Kinase (MEK)- hypoxia inducible factor 1 (HIF1) pathway.
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HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines. HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFalpha-inducible monocyte binding to HUVECs.
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Breast cancers often contain regions of reduced O2 which increases the activity of hypoxia-inducible factors (HIFs). HIFs have been shown to activate transcription of RhoA and ROCK1 leading to cytoskeletal changes that underlie the invasive cancer cell phenotype.
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It functions as a major molecular target for the immunosuppressive drugs such as ciclosporin. Five transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes.
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Efp, or estrogen-inducible RING-finger protein, is an E3 ubiquitin ligase that overexpression has been shown to be the major cause of estrogen-independent breast cancer. Efp's substrate is 14-3-3 protein which negatively regulates cell cycle.
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S. solfataricus cells aggregate preferentially with other cells of their own species. Frols et al. and Ajon et al. suggested that UV-inducible DNA transfer is likely an important mechanism for providing increased repair of damaged DNA via homologous recombination.
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A genetically encoded 3-hydroxypropionic acid inducible system has been characterized in bacteria demonstrating that such system in combination with fluorescent reporter protein can be utilized as a biosensor to measure intracellular and extracellular 3-HP concentrations by fluorescence output.
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Lysis has the advantage that it can stimulate the immune system and control growth. Multiple types of secretion systems can be used and other strategies as well. The system is inducible by external signals. Inducers include chemicals, electromagnetic or light waves.
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Reverse migration is the phenomena in which some neutrophils migrate away from the inflammation site, against the chemokine gradient, during inflammation resolution. The activation of in vivo inflammatory pathways (such as hypoxia- inducible factor, HIF), altered this behavior of reverse migration.
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There is evidence that FAM221B interacts with the proteins Autophagy related 13 (KIAA0652), RB1-inducible coiled-coil 1 (RB1CC1), and Ephrin-B3 (EFNB3) . These proteins are predicted to be localized in the nucleus at the same confidence level as FAM221B.
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Dicke M, van Poecke RMP, de Boer JG. Inducible indirect defence of plants: from mechanisms to ecological functions. Basic and Applied Ecology. 2003;4:27-42.Gatehouse JA. Plant resistance towards insect herbivores: a dynamic interaction. New Phytologist. 2002;156:145-69.
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Cells in the innate immune system have pattern recognition receptors that detect infection or cell damage in the cytosol. Three major classes of these cytosolic receptors are NOD–like receptors, RIG (retinoic acid-inducible gene)-like receptors, and cytosolic DNA sensors.
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HIF prolyl-hydroxylase is an enzyme involved in the HIF (Hypoxia-inducible factor) signalling pathways, and is the target for a set of therapeutic drugs called HIF prolyl-hydroxylase inhibitors. Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond physiologically to low concentrations of oxygen. A class of prolyl hydroxylases which act specifically on HIF has been identified; hydroxylation of HIF allows the protein to be targeted for degradation. HIF prolyl- hydroxylase has been targeted by a variety of inhibitors that aim to treat stroke, kidney disease, ischemia, anemia, and other important diseases.
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Higher loline concentrations (100–1000 μg/g) are present in the seeds and in younger leaf tissues, and the lolines display seasonal changes in concentration levels throughout the plant. The periodical appearance of tissues with high loline concentrations, such as flowering stems and seeds, contributes to this seasonal variation. Loline concentrations often increase in grass tissues regrown after defoliation and clipping of plants, suggesting an inducible defense response mechanism, involving both symbiotic partners. However, this increase appears to be due to higher loline levels in younger leaves compared to older leaves, but loline increases resembling inducible plant defenses have also been reported.
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The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4.
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The logical AND gate. If Signal A AND Signal B are present, then the desired gene product will result. All promoters shown are inducible, activated by the displayed gene product. Each signal activates expression of a separate gene (shown in light blue).
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It was first discovered in yeast and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).
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Recombination rates exceeded those of uninduced cultures by up to three orders of magnitude. Frols et al. and Ajon et al. hypothesized that the UV-inducible DNA transfer process and subsequent homologous recombinational repair represents an important mechanism to maintain chromosome integrity.
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Mukhopadhay et al. (1989) reported keratinase production by Streptomyces sp. He isolated an inducible extracellular homogenous enzyme, which shows a 7.5-fold increases in its activity after DEAE cellulose column chromatography. The enzyme-activity was inhibited by reduced glutathione, PMSF and 2-¬Mercaptaethanol.
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Recombination rates exceeded those of uninduced cultures by up to three orders of magnitude. Frols et al. and Ajon et al. hypothesized that the UV-inducible DNA transfer process and subsequent homologous recombinational repair represents an important mechanism to maintain chromosome integrity.
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This gene encodes a member of the hypoxia inducible gene 1 (HIG1) domain family. The encoded protein is localized to the cell membrane and has been linked to tumorigenesis and the progression of pituitary adenomas. Alternative splicing results in multiple transcript variants.
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On the other hand, nanomolar concentrations of adenosine activate A1 and A3 receptors, resulting in neutrophilic chemotaxis towards inflammatory stimuli. The release of ATP and an autocrine feedback through P2RY2 and A3 receptors are signal amplifiers. Hypoxia-inducible factors also influence adenosine signalling.
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Last, the electrophysiologist may administer various drugs (proarrhythmic agents) to induce arrhythmia (inducibility of VT/VF). If the arrhythmia is reproduced by the drugs (inducible), the electrophysiologist will search out the source of the abnormal electrical activity. The entire procedure can take several hours.
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Behnam, B., Iuchi, S., Fujita, M., Fujita, Y., Takasaki, H., Osakabe, Y., Yamaguchi-Shinozaki, K., Kobayashi, M., Shinozaki, K. 2013. Characterization of the promoter region of an arabidopsis gene for 9-cis-epoxycarotenoid dioxygenase involved in dehydration-inducible transcription. DNA Res. 20: 315-324.
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They send input to the brainstem which is then processed by respiratory centers. Other mechanisms include hypoxia-inducible factors, particularly HIF1. Hormonal changes have also been associated with HVR, particularly those that affect the functioning of the carotid bodies.Hornbein, Thomas F., and Robert B. Schoene.
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DNA-damage-inducible transcript 4 like (DDIT4L) or regulated in development and DNA damage response 2 (REDD2) is a protein that in humans is encoded by the DDIT4L gene Human. The gene is located on chromosome 4 or chromosome 3 in human or mouse respectively.
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Plants and herbivores have co-evolved together for 350 million years. Plants have evolved many defense mechanisms against insect herbivory. Such defenses can be broadly classified into two categories: (1) permanent, constitutive defenses, and (2) temporary, inducible defenses.Karban R, Baldwin IT. Induced responses to herbivory.
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Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and proteosomally digested in the presence of oxygen and iron. During normoxia GATA2 inhibits the promoter region for EPO. GATA2 levels decrease during hypoxia and allow the promotion of EPO production.
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CEF scientists developed a red-shifted two-photon-only caging group for three-dimensional photorelease. They also developed a minimal light‐switchable module enabling the formation of an intermolecular and conformationally well‐defined DNA G‐quadruplex structure with a photoswitchable azobenzene residue as part of the backbone structure. Important was also the development of an inducible fluorescent probe which enabled the detection of activity-dependent spatially localized miRNA maturation in neuronal dendrites. Using light-inducible antimiRs, CEF scientists also investigated if locally restricted target miRNA activity has a therapeutic benefit in diabetic wound healing and found that light can be used to locally activate therapeutically active antimiRs in vivo.
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AmpC type β-lactamases are commonly isolated from extended-spectrum cephalosporin-resistant Gram-negative bacteria. AmpC β-lactamases (also termed class C or group 1) are typically encoded on the chromosome of many Gram-negative bacteria including Citrobacter, Serratia and Enterobacter species where its expression is usually inducible; it may also occur on Escherichia coli but is not usually inducible, although it can be hyperexpressed. AmpC type β-lactamases may also be carried on plasmids. AmpC β-lactamases, in contrast to ESBLs, hydrolyse broad and extended-spectrum cephalosporins (cephamycins as well as to oxyimino-β- lactams) but are not inhibited by β-lactamase inhibitors such as clavulanic acid.
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Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the HIF1A gene. It is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. The dysregulation and overexpression of HIF1A by either hypoxia or genetic alternations have been heavily implicated in cancer biology, as well as a number of other pathophysiologies, specifically in areas of vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. Two other alternative transcripts encoding different isoforms have been identified.
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Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene. Recent research has shown that AIM2 is part of the inflammasome and contributes to the defence against bacterial and viral DNA.
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Epub 2007 Apr 21. The mRNA transcription of Nkd genes is inducible by Wnt signaling in diverse animals, such that nkd expression is a readout of Wnt activity.Chang JL, Chang MV, Barolo S, Cadigan KM. Regulation of the feedback antagonist naked cuticle by Wingless signaling. Dev Biol.
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Human activation-inducible tumor necrosis factor receptor (AITR) and its ligand, AITRL, are important costimulatory molecules in the pathogenesis of autoimmune diseases. Despite the importance of these costimulatory molecules in autoimmune disease, their role in the autoimmune reaction to herniated disc fragments has yet to be explored.
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Tyrosine-protein kinase ITK/TSK also known as interleukin-2-inducible T-cell kinase or simply ITK, is a protein that in humans is encoded by the ITK gene. ITK is a member of the TEC family of kinases and is highly expressed in T cells.
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Dimarcq, J.L., D. Zachary, J.A. Hoffmann, D. Hoffmann, and J.M. Reichhart. "Insect immunity: expression of the two major inducible antibacterial peptides, defensin and diptericin, in Phormia terranovae." EMBO J. 9: 2507-515. To prevent infection, P. terraenovae maggots must be raised in vitro under sterile conditions.
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The intensity of the stains for TNF-α and inducible nitric oxide synthase (iNOS) of the myocardium was greater in patients with HIV associated cardiomyopathy (as opposed to idiopathic cardiomyopathy), myocardial viral infection and was inversely correlated with CD4 count with antiretroviral therapy having no effect.
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This inhibition leads to the stabilisation of a number of hypoxia-inducible factors which are thought to predispose to tumorigensis. An alternative pathway for the metabolism of fumarate in the presence of these mutations has been described. Other genes involved affected by this mutation are Keap1, Nrf2 and HMOX1.
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Owing to its predictable organization and readily inducible LTP, the CA1 hippocampus has become the prototypical site of mammalian LTP study. In particular, NMDA receptor-dependent LTP in the adult CA1 hippocampus is the most widely studied type of LTP, and is therefore the focus of this article.
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Recovery from chronic hepatitis C in long- term responders to ribavirin plus interferon-alpha. Lancet, 2000; 356: 41. #Gordien, E., Rosmorduc, O., Peltekian, C., Garreau, F., Brechot, C., and Kremsdorf, D. Inhibition of hepatitis B virus replication by the interferon- inducible MxA protein. Journal of Virology, 2001; 75:2684.
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Chicago: Chicago University Press; 1997. Both types are achieved through similar means but differ in that constitutive defenses are present before an herbivore attacks, while induced defenses are activated only when attacks occur.Chen MS. Inducible direct plant defence against insect herbivores: a review. Insect Science. 2008;15:101-14.
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Inducible defenses allow plants to be phenotypically plastic. This may confer an advantage over constitutive defenses for multiple reasons. First, it may reduce the chance that attacking insects adapt to plant defenses.Karban R, Agrawal AA, Mangel M. The benefits of induced defenses against herbivores. Ecology. 1997;78:1351-5.
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Induced defense stemming from adaptive phenotypic plasticity may help a plant defend itself against multiple enemies.Agrawal, Anurag A. "Induced plant defense: evolution of induction and adaptive phenotypic plasticity." Inducible plant defenses against pathogens and herbivores: biochemistry, ecology, and agriculture. American Phytopathological Society Press, St. Paul, MN (1999): 251-268.
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Acute changes in hematocrit are the result of circulating stress hormones (see - catecholamines) activating receptors on the spleen that cause the release of RBCs into circulation. During chronic hypoxia exposure, the mechanism used to increase hematocrit is independent of the spleen and results from hormonal stimulation of the kidney by erythropoetin (EPO). Increasing hematocrit in response to erythropoietin is observed after approximately one week and is therefore likely under genetic control of hypoxia inducible factor hypoxia inducible factor (HIF). While increasing hematocrit means that the blood can carry a larger total amount of oxygen, a possible advantage during hypoxia, increasing the number of RBCs in the blood can also lead to certain disadvantages.
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Fornace has made a variety of notable discoveries in the fields of cancer research, molecular biology, radiation biology, and toxicology with particular emphasis on understanding stress-signaling mechanisms in both normal and cancer cells. This has focused on understanding how cells and organisms respond to genotoxic (DNA damaging) agents, such as radiation, that can cause cancer – as well as being used for its treatment. He was one of the first to show that human and other mammalian cells can respond at the gene level to genotoxic stress, and isolated many of the first known DNA-damage-inducible genes.Fornace, A. J., Jr, Alamo, I. J., and Hollander, M. C. DNA damage-inducible transcripts in mammalian cells.
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Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) also known as activation-inducible TNFR family receptor (AITR) or glucocorticoid-induced TNFR-related protein (GITR) is a protein that in humans is encoded by the TNFRSF18 gene. GITR is currently of interest to immunologists as a co- stimulatory immune checkpoint molecule.
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This would result in a poorly developed transplastomic plant with low product yield. Inducible expression expression of the transgene would overcome this limitation and allow the plant to mature fully like a normal wildtype plant before it is induced chemically to begin production of the transgene which can then be harvested.
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This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
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The genes (EPAS1, EGLN1, and PPARA) function in concert with another gene named hypoxia inducible factors (HIF), which in turn is a principal regulator of red blood cell production (erythropoiesis) in response to oxygen metabolism. The genes are associated not only with decreased haemoglobin levels, but also in regulating energy metabolism.
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The product encoded by this gene belongs to the heat shock protein 70 family which contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate proteins. This gene encodes a heat-shock cognate protein. This protein plays a role in the control of cell proliferation.
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Prolactin-inducible protein also known as gross cystic disease fluid protein 15 (GCDFP-15), extra-parotid glycoprotein (EP-GP), gp17 seminal actin-binding protein (SABP) or BRST2 is a protein that in humans is encoded by the PIP gene. It is upregulated by prolactin and androgens and downregulated by estrogen.
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Another costimulatory receptor expressed by T cells is ICOS ( Inducible Costimulator), which interacts with ICOS-L. T cell co-stimulation is necessary for T cell proliferation, differentiation and survival. Activation of T cells without co- stimulation may lead to T cell anergy, T cell deletion or the development of immune tolerance.
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Minocycline is also known to indirectly inhibit inducible nitric oxide synthase. A trial found no difference between minocycline and placebo in people with Alzheimers' disease. Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is somewhat neuroprotective in mouse models of Huntington's disease.
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It is common among protists that the sexual cycle is inducible by stressful conditions such as starvation. Such conditions often cause DNA damage. A central feature of meiosis is homologous recombination between non-sister chromosomes. In T. thermophila this process of meiotic recombination may be beneficial for repairing DNA damages caused by starvation.
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The heat shock protein 70 (Hsp70) family contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate (Hsc) proteins. The heat shock 70 kDa protein 8 also known as Hsc70 belongs to the heat-shock cognate subgroup. This protein binds to nascent polypeptides to facilitate correct protein folding.
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Mutation Research. 376: 37-41. In addition, some of these metabolic enzymes are inducible and have polymorphic variation. CYP1A2 displays a 40-fold variation in expression among humans and can be induced by smoking, diet, and chronic hepatitis.Schweikl, H., et al (1993) Expression of CYP1A1 and CYP1A2 genes in human liver. Pharmacogenetics.
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Sarcosine oxidase is an enzyme () that catalyzes the oxidative demethylation of sarcosine to yield glycine, H2O2, 5,10-CH2-tetrahydrofolate in a reaction requiring H4-tetrahydrofolate and oxygen. Corynebacterial sarcosine oxidase is a heterotetramer and is produced as an inducible enzyme when Corynebacterium sp.is grown with sarcosine as source of carbon and energy.
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Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the SOCS3 gene. This gene encodes a member of the STAT- induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.
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Proteasome subunit alpha type-6 is a protein that in humans is encoded by the PSMA6 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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Proteasome subunit alpha type-2 is a protein that in humans is encoded by the PSMA2 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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Proteasome subunit alpha type-1 is a protein that in humans is encoded by the PSMA1 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, and beta5i) that contributes to the complete assembly of 20S proteasome complex.
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CYFIP2 has been shown to interact with FMR1. CYFIP2 is a p-53 inducible protein and also interacts with the Fragile=X mental retardation protein.Schenck, A., Bardoni, B., Moro, A., Bagni, C., Mandel, J.-L. (2001) Proceedings of the National Academy of Sciences of the United States of America, 98, 8844-8849.
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Currently unknown but editing may have role in regulation of apoptotic functions of this protein. It is thought that since the protein is p53 inducible that the protein may be pro- apopototic. Also ADAR1 knock out mice show increase in apoptosis which indicates editing may be involved in regulation of the cellular process.
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8) and the functionally uncharacterized DNA damage-inducible protein F (DinF; TC# 2.A.66.1.4) of E. coli. The family includes hundreds of functionally uncharacterized but sequenced homologues from bacteria, archaea, and all eukaryotic kingdoms. A representative list of proteins belonging to the MATE family can be found in the Transporter Classification Database.
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Krüppel has shown homology to the mammalian Krüppel-like factors, which play key biological roles in the pathogenesis of many human diseases: cancer, obesity, inflammatory disorders and cardiovascular complications. Moreover, KLFs are known to be involved in inducible pluripotent stem cells generation, and preservation of the pluripotent state of embryonic stem cells.
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Data on the genetic basis for HAPE susceptibility is conflicting and interpretation is difficult. Genes implicated in the development of HAPE include those in the renin-angiotensin system (RAS), NO pathway, and hypoxia-inducible factor pathway (HIF). Future genomic testing could provide a clearer picture of the genetic factors that contribute to HAPE.
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In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. mir-210 has been strongly linked with the hypoxia pathway, and is upregulated in response to Hypoxia-inducible factors. It is also overexpressed in cells affected by cardiac disease and tumours.
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It harbors a regulatory DNA sequence called the long terminal repeat (LTR), which promotes steroid- hormone-inducible transcription. Tumorgenesis that was induced by the mouse mammary tumor virus can also be done by integration of the viral genome. The sites of integration have been known to be critical genes for cellular regulation.Ross, RS. (2010).
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6(3): p. 809. Since the C repressor is not inactivated by the SOS/RecA system of E. coli, the P2 prophage is non-inducible by ultraviolet irradiation. Furthermore, even if C repressor is inactivated, the P2 prophage is unable to excise, due to lack of int expression.Bertani, L.E., Abortive induction of bacteriophage P2.
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MET transcription is activated by HGF and several growth factors. MET promoter has four putative binding sites for Ets, a family of transcription factors that control several invasive growth genes. ETS1 activates MET transcription in vitro. MET transcription is activated by hypoxia-inducible factor 1 (HIF1), which is activated by low concentration of intracellular oxygen.
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The umu test, first developed and published by Oda et al., is based on the ability of DNA-damaging agents to induce the expression of the umu operon. In connection with the damage inducible genes (din genes) recA, lexA and umuD, the umuC gene is essentially involved in bacterial mutagenesis through the SOS response.
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The response of naked carp to cold and low-oxygen conditions seem to be at least partly mediated by hypoxia-inducible factor 1 (HIF-1). It is unclear whether this is a common characteristic in other high altitude dwelling fish or if gill remodelling and HIF-1 use for cold adaptation are limited to carp.
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These bacteria can be found almost everywhere in soil, water, wastewater, etc. They can also be found in the human intestine. They are rarely the source of illnesses, except for infections of the urinary tract and infant meningitis and sepsis. C. freundii strains have inducible ampC genes encoding resistance to ampicillin and first-generation cephalosporins.
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The resting expression of GPR84 is usually low but it is highly inducible in inflammation. Its expression on neutrophils can be increased with LPS stimulation and reduced with GM-CSF stimulation. The LPS- induced upregulation of GPR84 was not sensitive to dexamathasone pretreatment. There was also a GPR84 downregulation in dentritic cell derived from FcRgamma chain KO mice.
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However, it appears that autophagy can help in cancer cell survival under conditions of metabolic stress and it may confer resistance to anti-cancer therapies such as radiation and chemotherapy. Additionally, in the microenvironment of cancer cells, there is an increase in hypoxia-inducible transcription factor 1-alpha (HIF1A), which promotes expression of BNIP3, an essential factor for mitophagy.
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All promoters shown are inducible. The activating promoter for the output gene is constitutive, and thus not shown. The constitutive promoter for the output gene keeps it "on" and is only deactivated when (similar to the AND gate) a complex as a result of two input signal gene products blocks the expression of the output gene.
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During recombination two strands of DNA exchange information. This recombination will cause a deletion or inversion of the genes between the two lox sites, depending on their orientation. An entire gene can be removed to inactivate it. This whole system is inducible so a chemical can be added to knock genes out at a specific time.
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Other immune factors found in the testis include the enzyme inducible nitric oxide synthase (iNOS), and its product nitric oxide (NO), transforming growth factor beta (TGFβ), the enzyme cyclooxygenase-2 (COX-2) and its product prostaglandin E2, and many others. Further research is required to define the functional roles of these immune factors in the testis.
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The pathophysiology of palinopsia remains unclear. The immediate type may be an exaggeration of the afterimage whereas the delayed type may indicate that there is cerebral involvement, such as an ictal manifestation or a structural lesion, but has also been shown to be inducible by drugs. The differential diagnosis includes toxins, metabolic disorders and psychiatric conditions.
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On the contrary, Oma1 only generates N- and C-terminal proteolytic fragments. It has been showed that the mammalian mitochondrial inner membrane fusion protein OPA1 can be degraded by OMA1 when mitochondria lose membrane potential or adenosine triphosphate. Such inducible proteolysis acts as a regulatory mechanism to proteolytically inactivate OPA1, thus preventing the fusion of the mitochondrial network.
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Some constituents of myoga are cytotoxic; others have shown promise for potentially anticarcinogenic properties.Ha Won Kim et al. "Suppressive Effects of Mioga Ginger and Ginger Constituents on Reactive Oxygen and Nitrogen Species Generation, and the Expression of Inducible Pro-Inflammatory Genes in Macrophages," Antioxidants & Redox Signaling. November/December 2005, 7(11-12): 1621-1629; retrieved 2013-8-4.
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The inducible protein isoform, iPFK2, is named as such because its expression has been shown to be induced by hypoxic conditions. The PFKFB3 promoter is predicted to contain multiple binding sites, including Sp-1 and AP-2 binding sites. It also contains motifs for the binding of E-box, nuclear factor-1 (NF-1), and progesterone response element.
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The product of this gene belongs to the family of prolyl 4-hydroxylases. This protein is a prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. It plays a role in adaptation to hypoxia and may be related to cellular oxygen sensing. Alternatively spliced variants encoding different isoforms have been identified.
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Shelton AL. Variation in chemical defenses of plants may improve the effectiveness of defense. Evolutionary Ecological Research 2004;6:709-26. Simply, inducible defenses cause variations in the defense constituents of a plant, thereby making the plant a more unpredictable environment for insect herbivores. This variability has an important effect on the fitness and behaviour of herbivores.
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Intrinsic anti-tumor and anti- angiogenic functions of type I interferons. RIG-1 mediated SeV IFN-beta stimulation. Retinoic Acid Inducible Gene 1 (RIG-I) is a key mediator of antiviral immunity, able to couple detection of infection by RNA viruses to the induction of interferons. Full-length Sendai virus genomic RNA bearing 5′-triphosphates triggers IFN-beta production.
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Insect Immunity: septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides. Journal of Biological Chemistry, 269 (1994), pp. 33159–33163L. Michaut, P. Fehlbaum, M. Moniatte, A. Van Dorsselaer, J.M. Reichhart, P. Bulet. Determination of the disulfide array of the first inducible antifungal peptide from insects: drosomycin from Drosophila melanogaster.
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Nuclear Enriched Abundant Transcript 1 (NEAT1) is a ~3.2 kb novel nuclear long non-coding RNA (RIKEN cDNA 2310043N10Rik). It is also known as Virus Inducible NonCoding RNA (VINC) or MEN epsilon RNA. It is transcribed from the multiple endocrine neoplasia locus. Expression of NEAT1 is induced in mouse brains during infection by Japanese encephalitis virus and rabies virus.
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Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ.
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Hypoxia stimulates hypoxia-inducible factor-1 alpha (HIF-1α) to be produced, which initiates the hypoxic response. HIF-1α induces the transcription of BHLHE41 and BHLHE40. This is believed to repress cell proliferation, which is not conducive to a hypoxic environment. BHLHE41 can also block a hypoxic response by presenting HIF-1α to a proteasome complex, which induces HIF-1α's degradation.
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Recently, it has been shown that certain promoters are capable of directing transcription inside regions that are otherwise silenced by SIR proteins. Specifically, if an inducible promoter is induced inside a silent chromatin domain, it can achieve ~200x increase in expression levels with little detectable change in covalent histone modifications. SIR spreading is thought to occur linearly from the silencer element.
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Another way for bacteria to defend against phage infection is by having chromosomal islands. A subtype of chromosomal islands called phage-inducible chromosomal island (PICI) is excised from a bacterial chromosome upon phage infection and can inhibit phage replication. PICIs are induced, excised, replicated and finally packaged into small capsids by certain staphylococcal temperate phages. PICIs use several mechanisms to block phage reproduction.
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Forkhead box protein N3 is a protein that in humans is encoded by the FOXN3 gene. This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway.
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Inducible BALT is formed after infection, e.g. influenza, and peak in size between 1 and 2 weeks after infection and diminish thereafter. Immune responses initiated in iBALT are delayed relative to the immune response in the draining lymph nodes, owing to the time it takes to form iBALT. However, in chronic disease iBALT may be a component of the pathology.
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Neurogenesis continues after development well through adulthood. Growth arrest and DNA-damage-inducible, beta (GADD45b) is required for the demethylation of promoters of critical genes responsible for new-born neuron development such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF2). As such, upregulation of GADD45b leads to increased demethylation, increased BDNF and FGF2, and ultimately more neural progenitor cells.
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The promoter initiates the transcription and is therefore the point of control for the expression of the cloned gene. The promoters used in expression vector are normally inducible, meaning that protein synthesis is only initiated when required by the introduction of an inducer such as IPTG. Gene expression however may also be constitutive (i.e. protein is constantly expressed) in some expression vectors.
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Accessed December 27, 2006. e.g. from macrophages and platelets when in a low- oxygen environment. Endothelial growth and proliferation is also directly stimulated by hypoxia, and presence of lactic acid in the wound. For example, hypoxia stimulates the endothelial transcription factor, hypoxia-inducible factor (HIF) to transactivate a set of proliferative genes including vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1).
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Most of the inherited SDHC gene mutations change single amino acids in the SDHC protein sequence or result in a shortened protein. As a result, there is little or no SDH enzyme activity. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. The excess succinate abnormally stabilizes hypoxia-inducible factors (HIF), which also builds up in cells.
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McJunkin earned a bachelor of arts from Princeton University in 2005. She completed a Ph.D. in biological sciences at Watson School of Biological Sciences at Cold Spring Harbor Laboratory in 2010. She completed her dissertation, Inducible RNAi targeting essential genes, under advisor Scott W. Lowe. McJunkin was a postdoctoral fellow at University of Massachusetts Medical School from 2011 to 2017.
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Once the resulting proteins are translated, PRR9, PRR7, and PRR5 repress RVE8. RVE8 also interacts with the NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED (LNK1, 2, 3, and 4) morning components, with LNKs either antagonizing or co-activating RVE8. Although GIGANTEA (GI) is not known as a core part of the Arabdopsis TTFL model, it is repressed by CCA1, LHY and TOC1.
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It has a long N-terminal CstA domain and a short C-terminal DUF4161 domain. This protein is encoded by a carbon starvation inducible gene, cstA, that is under cyclic AMP-CRP control. Circumstantial evidence suggested that it may be a peptide transporter. A Campylobacter jejuni homologue has been shown to transport di- and tripeptides (see TC# 2.A.114.1.5).
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4082-90 Berra E, et al., « The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling », EMBO Rep, (2006) 7, p. 41-5. Review Pouysségur et al., « Hypoxia signalling in cancer and approaches to enforce tumour regression », Nature, (2006) 441, p. 437-43, nutritional stress and aberrant tumor metabolismKroemer G., et al., « Tumor cell metabolism: cancer's Achilles' », Cancer Cell.
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Cytochrome P450, family 52, also known as CYP52, is a cytochrome P450 family in fungi participate in the assimilation of alkanes and fatty acids, which the most ancient function was the oxidation of C4-C11 alkanes. The first gene identified in this family is the alkane-inducible cytochrome P450 (P450alk) gene from the yeast Candida tropicalis, with CYP Symbol CYP52A1.
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Chronic hypoxia results in further physiological changes due to the transcription factor hypoxia-inducible factor (HIF). HIF is a dimer composed of the HIF-1α and HIF-1β subunit. HIF-1α is normally unable to bind with HIF-1β. However, lower oxygen partial pressure induces post-transcriptional modification of HIF-1α, allowing HIF-1α to dimerize with HIF-1β to form HIF-1.
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ASUN is located downstream and TM7SF3 is located slightly upstream from the FGFR1OP2 gene locus. There are three transcript variants for the FGFR1OP2 gene, with the first being the longest. FGFR1OP2 is also known as HSPC123-like protein (HSPC123L) and wound inducible transcript 3.0 (wit3.0). The promoter region of the Homo sapiens FGFR1OP2 gene shown with likely binding sites for transcription factors.
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Gal80 is an inhibitor of GAL4, and will suppress GFP expression under normal conditions. This tubP-GAL80 element is placed distal to an FRT site. A second FRT site is placed in trans to the GAL80 site, usually with a gene or mutation of interest distal to it. Finally, FLP recombinase is driven by an inducible promoter such as heat shock.
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If there is sustained inflammation and injury, PaSC activation is perpetuated, resulting in the growth of pancreatic fibrosis. The activation of P2 receptors induces intracellular calcium signalling which mediates the fibrogenic function of activated stellate cells. However, if inflammation and injury is minor, PaSCs undergo an apoptotic fate and become quiescent, preventing the development of fibrosis. PaSCs also display ethanol inducible ADH activity.
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The von Hippel-Lindau tumor suppressor gene generally has a germline mutation. This suppressor gene is also called elongin binding protein and G7 protein. The VHL protein is involved in up-regulation of hypoxic response via the hypoxia inducible factor [HIF]-1 alpha. Mutations generally prevent the production of any functional VHL protein or result in a change of structure of VHL protein.
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Some Sp100 variants contain a domain similar to two interferon-inducible nuclear phosphoproteins, suppressin and DEAF1. This defines a novel protein motif, the HNPP-box. Another class of variants has high mobility group 1 (HMG1) protein sequence as a domain. Both major classes of Sp100 splice variant proteins localize in part to nuclear dots/PML bodies and other nuclear domains.
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Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1α. PHDs hydroxylate proline in parallel to oxidatively decarboxylating 2-oxyglutarate to succinate and CO2. In humans, three HIF prolyl 4-hydroxylases regulate the stability of HIFs. Hydroxylation of two prolyl residues in HIF1α facilitates ubiquitin ligation, thus marking it for proteolytic destruction by the ubiquitin/proteasome pathway.
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Chemical background. In: Ergot Alkaloids and Related Compounds (Berde, B. & Schild, H.O., eds.) Berlin: Springer-Verlag. Related compounds are found across the range of endophytic fungal associations with plants. The terpenes and alkaloids are inducible defenses which act similarly to defensive compounds produced by plants and are highly toxic to a wide variety of phytophagous insects as well as mammalian herbivores.
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Proteasome subunit alpha type-3 also known as macropain subunit C8 and proteasome component C8 is a protein that in humans is encoded by the PSMA3 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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LT-α is translated as a 25 kDa glycosylated polypeptide with 171 amino acid residues. Furthermore, human LT-α is 72% identical to mouse LT-α at the protein's primary sequence. LTα expression is highly inducible and when secreted, forms a soluble homotrimeric molecule. LT-α can also form heterotrimers with lymphotoxin-beta, which anchors lymphotoxin-alpha to the cell surface.
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Alcoholic liver disease is a common medical consequence of chronic alcohol abuse. Activation of hypoxia-Inducible Factor-1α (HIF-1α) is an indicator of hypoxia. Endothelin-1 (ET-1) is a protein that constricts blood vessels and raises blood pressure. It has been shown that ethanol-induced miR-199 down- regulation may contribute to augmented HIF-1α and ET-1 expression.
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Proteasome subunit alpha type-7 also known as 20S proteasome subunit alpha-4 is a protein that in humans is encoded by the PSMA7 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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Proteasome subunit alpha type-5 also known as 20S proteasome subunit alpha-5 is a protein that in humans is encoded by the PSMA5 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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Egl nine homolog 2 is a protein that in humans is encoded by the EGLN2 gene. ELGN2 is an alpha-ketoglutarate-dependent hydroxylase, a superfamily of non- haem iron-containing proteins. The hypoxia inducible factor (HIF) is a transcriptional complex which is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degradation by prolyl hydroxylation.
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Most dehydrogenases show induced expression in the bacterial cell in response to metabolic needs triggered by the environment in which the cells grow. In the case of lactate dehydrogenase in E.coli, the enzyme is used aerobically and in combination with other dehydrogenases. It is inducible and is expressed when there is high concentration of DL- lactate present in the cell.
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Poly(A)-binding proteins (PABPs) bind to the poly(A) tail present at the 3-prime ends of most eukaryotic mRNAs. PABPC4 or IPABP (inducible PABP) was isolated as an activation-induced T-cell mRNA encoding a protein. Activation of T cells increased PABPC4 mRNA levels in T cells approximately 5-fold. PABPC4 contains 4 RNA-binding domains and proline-rich C terminus.
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Collagen consists of both 3‐hydroxyproline and 4‐hydroxyproline residues. Hydroxylation occurs at the γ-C atom, forming hydroxyproline (Hyp), which stabilizes the secondary structure of collagen due to the strong electronegative effects of oxygen. Proline hydroxylation is also a vital component of hypoxia response via hypoxia inducible factors. In some cases, proline may be hydroxylated instead on its β-C atom.
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Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. The HMOX gene is located on the long (q) arm of chromosome 22 at position 12.3, from base pair 34,101,636 to base pair 34,114,748.
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Inducible NO synthase (iNOS) is responsible for the generation of nitrogen radicals in the cell and it is activated after binding of NF-κβ to promoter. iPSC forms oxygen radicals only in the initial phase of reprogramming. Later oxidation activity attenuates and up-regulation of antioxidant enzymes occurs. The correct timing and amount of ROS / NOS is critical to the overall efficiency of the process.
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1:P. pastoris is able to grow on simple, inexpensive medium, with high growth rate. P. pastoris can grow in either shake flasks or a fermenter, which makes it suitable for both small- and large-scale production. 2:P. pastoris has two alcohol oxidase genes, Aox1 and Aox2, which include strongly inducible promoters. These two genes allow Pichia to use methanol as a carbon and energy source.
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The mechanism behind this inhibition is still unknown. Thirdly, kalkitoxin blocks the electron transport chain (ETC) complex 1, one of the protein complexes involved in mitochondrial respiration. By blocking the ETC complex 1, kalkitoxin potently inhibits hypoxia-inducible factor-1 (HIF-1) activation. HIF-1 is a transcription factor, which enhances the expression of genes that increase oxygen availability, as well as genes that decrease oxygen consumption.
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Eldelumab (alternative identifier BMS-936557) is a fully human monoclonal antibody (type IgG1 kappa) that targets chemokine (C-X-C motif) ligand 10 (CXCL10)/Interferon-γ-inducible protein-10 (IP-10) designed for the treatment of Crohn's disease and ulcerative colitis.Statement On A Nonproprietary Name Adopted By The USAN Council - Eldelumab, American Medical Association. This drug was developed by Bristol-Myers Squibb and Medarex.
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This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. The Sestrins constitute a family of evolutionarily-conserved stress-inducible proteins that suppress oxidative stress and regulate adenosine monophosphate-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling.
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The expressed proteins then can either form a complete complex in cytosol, that is capable of activating expression of the output (shown), or can act separately to induce expression, such as separately removing an inhibiting protein and inducing activation of the uninhibited promoter. The logical OR gate. If Signal A OR Signal B are present, then the desired gene product will result. All promoters shown are inducible.
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Upon tissue disruption they get into contact with β-glucosidases from the chloroplasts, which enzymatically release the toxic aglucones. Whereas some benzoxazinoids are constitutively present, others are only synthesised following herbivore infestation, and thus, considered inducible plant defenses against herbivory. The terpenoids, sometimes referred to as isoprenoids, are organic chemicals similar to terpenes, derived from five-carbon isoprene units. There are over 10,000 known types of terpenoids.
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One of the various ways to exert control over CAR T cell is through drug-controlled synthetic systems. iCasp9 was created by modifying caspase-9 and fusing it with the FK506 binding protein. iCasp9 can be added to the CAR T cells as an inducible suicide gene. If therapy with CAR T cells results in severe side effects, iCasp9 can be used to halt treatment.
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Hemangioblastomas are composed of endothelial cells, pericytes and stromal cells. In VHL syndrome the von Hippel-Lindau protein (pVHL) is dysfunctional, usually due to mutation and/or gene silencing. In normal circumstances, pVHL is involved in the inhibition of hypoxia-inducible factor 1 α (HIF-1α) by ubiquitin mediated proteosomal degradation. In these dysfunctional cells pVHL cannot degrade HIF-1α, causing it to accumulate.
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Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3. This protein promotes intrinsic apoptosis in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α). As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.
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The von Hippel-Lindau tumour suppressor protein (pVHL) ubiquitinates hypoxia-inducible factor 1α (HIF1α) when cell oxygen levels are normal. This leads to the degradation of HIF1α and prevents the transcription of hypoxic response genes such as vascular endothelial growth factor, platelet-derived growth factor B, and erythropoietin. USP20 deubiquitinates HIF1α, preventing its proteasomal degradation, and allows it to transcribe the hypoxic response genes.
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A Spanish study, involving enteric pathogens also found that 32 strains of H. alvei were universally susceptible to all quinolones (including gemifloxacin and grepafloxacin), cefotaxime, gentamicin, co-trimoxazole, and naladixic acid; 78% of the strains in that study were susceptible to doxycycline. Some H. alvei strains produce both low-level inducible cephalosporinases (ceftazidime susceptible) and high-level constitutive cephalosporinase activity that is resistant to ceftazidime.
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PKM2 is a cytosolic enzyme that is associated with other glycolytic enzymes, i.e., hexokinase, glyceraldehyde 3-P dehydrogenase, phosphoglycerate kinase, phosphoglyceromutase, enolase, and lactate dehydrogenase within a so- called glycolytic enzyme complex. However, PKM2 contains an inducible nuclear localization signal in its C-terminal domain. The role of PKM2 within the nucleus is complex, since pro-proliferative but also pro-apoptotic stimuli have been described.
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Blue Mussels are able to fight off one species of predator at a time such as sea star(Asterias Rubens (=Asterias Vulgaris)) or green crabs (Carcinus maenas). They use their inducible defenses to strengthen their adductor muscle or grow thicker shells. When faced with two species at a time, they are no longer able to use their defenses and can be killed more easily.
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The Umu Chromotest, first developed and published by Oda et al., is a biological assay (bioassay) to assess the genotoxic potential of chemical compounds. It is based on the ability of DNA-damaging agents to induce the expression of the umu operon. In connection with the damage inducible (din) genes recA, lexA and umuD, the umuC gene is essentially involved in bacterial mutagenesis through the SOS response.
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S. maltophilia is naturally resistant to many broad-spectrum antibiotics (including all carbapenems) due to the production of two inducible chromosomal metallo-β-lactamases (designated L1 and L2). This makes treatment of infected patients very difficult. S. maltophilia is ubiquitously present in the environment and impossible to eradicate, which makes prevention also extremely difficult. Sensitivity testing requires nonstandard culture techniques (incubation at 30 °C).
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Proteasome subunit alpha type-4 also known as macropain subunit C9, proteasome component C9, and 20S proteasome subunit alpha-3 is a protein that in humans is encoded by the PSMA4 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
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The activation of T lymphocytes and Natural Killer (NK) Cells, both in vivo and in vitro, induces expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as a signal-transmitting receptor in lymphocytes, including natural killer (NK) cells, and platelets (Cambiaggi et al., 1992) [supplied by OMIM].
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In April 2017, Merck Animal Health acquired Brazilian animal health product manufacturer, Vallée S.A. In September, the company announced it would acquire Rigontec for $554 million, acquiring Rigontec's lead compound RGT100, which targets the retinoic acid- inducible gene I pathway. In February 2018, Merck announced it would acquire Australian viral cancer drug company, Viralytics for AUD$502 million ($394 million), boosting Merck's own pipeline.
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CHOP can downregulate the expressions of anti-apoptotic BCL2 proteins, and upregulate the expression of proapoptotic proteins (BIM, BAK and BAX expression). BAX-BAK oligomerization causes cytochrome c and apoptosis-inducing factor (AIF) release from mitochondria, eventually causing cell death. TRB3 pseudokinase is upregulated by the ER stress-inducible transcriptional factor, ATF4-CHOP. CHOP interacts with TRB3, which contributes to the induction of apoptosis.
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Radiation-inducible immediate-early gene IEX-1 is a protein that in humans is encoded by the IER3 gene. This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein.
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Bacterial species with two genes for alanine racemase have one that is continually expressed and one that is inducible, which makes it difficult to target both genes for drug studies. However, knockout studies have shown that without the alr gene being expressed, the bacteria would need an external source of D-alanine in order to survive. Therefore, the alr gene is a feasible target for antimicrobial drugs.
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HIF1α causes the transcription of genes that contain the hypoxia response element. In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. The VHL protein (pVHL) is involved in the regulation of a protein known as hypoxia inducible factor 1α (HIF1α). This is a subunit of a heterodimeric transcription factor that at normal cellular oxygen levels is highly regulated.
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Preisser EL, Gibson SE, Adler LS, Lewis EE. Underground herbivory and the costs of constitutive defense in tobacco. Acta Oecol-Int J Ecol. 2007;31:210-5. This results suggest that there is a biosynthetic cost to constantly producing a high level of defensive chemicals. Inducible defences are advantageous as they reduce the metabolic load on the plant in conditions where such biological chemicals are not yet necessary.
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Induction of autophagy results in the dephosphorylation and activation of the ULK kinases. ULK is part of a protein complex containing Atg13, Atg101 and FIP200. ULK phosphorylates and activates Beclin-1 (mammalian homologue of Atg6), which is also part of a protein complex. The autophagy-inducible Beclin-1 complex contains the proteins PIK3R4(p150), Atg14L and the class III phosphatidylinositol 3-phosphate kinase (PI(3)K) Vps34.
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This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein- protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53, retinoblastoma-1 and BRCA1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway.
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Hypoxic condition in stem cell niches (ESC, ASC or CSC) is necessary for maintaining stem cells in an undifferentiated state and also for minimizing DNA damage via oxidation. The maintaining of the hypoxic state is under control of Hypoxia-Inducible transcription Factors (HIFs). HIFs contribute to tumour progression, cell survival and metastasis by regulation of target genes as VEGF, GLUT-1, ADAM-1, Oct4 and Notch.
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The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS), also known as STAT-induced STAT inhibitor (SSI), protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.
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The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF-alpha and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 (death receptor 3) and TNFRSF6B (decoy receptor 3).
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Phosphorylation of the FOXO1 protein is a result of the activation of the PI3K /AKT pathway. Serum and glucocorticoid-inducible kinase SGK can also phosphorylate and inactivate FOXO1 transcription factor. FOXO1 translocate from the nucleus to cytoplasm and inactivate through phosphorylation at well-defined sites by AKT/SGK1 protein kinases. FOXO1 transcription factor can phosphorylate directly by AKT/SGK1 on three sites T24, S256 and S319.
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A research done by Zaibo Li et. al displayed the KRAB-A-Domain in action. The von-Hippel Lindau tumor suppressor (pVHL) is a part of protein complex known as E3 ubiquitin ligase and targets hypoxia-inducible-factor 1a (HIF-1a) for breakdown. It is reported that there is a new protein that was discovered that interacts with the pVHL protein and helps it with its job.
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Their attempt was too effective, as it was now too difficult to induce transcription in highly repressed variants. Huang and Lindblad 2013 created a library of modified pTet promoters with varying levels of repression and dynamic range in the glucose tolerant Synechocystis sp. ATCC 27184. Another option are promoters that are inducible by heavy metals, such as: zinc, cadmium, cobalt, arsenic, nickel and chromium.
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There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors. This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis.
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The quantitative lineage-tracing strategies have proven to be successful in resolving cell fates in normal epithelial tissues either using tissue –specific or stem-cell-specific transgenes. To conduct an inducible lineage-tracing experiment two components must be engineered into the mouse genome: a switch and a reporter. The switch is commonly a drug- regulated form of the bacterial enzyme Cre-recombinase. This enzyme recognizes specific sequences, called LoxP sites.
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The two most commonly used inducible expression systems for research of eukaryote cell biology are named Tet-Off and Tet-On.Tet-On and Tet-Off are registered trademarks of Clontech Laboratories, Inc. in the United States. The Tet-Off system for controlling expression of genes of interest in mammalian cells was developed by Professors Hermann Bujard and Manfred Gossen at the University of Heidelberg and first published in 1992.
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HIF-1 is a transcription factor which induces expression of genes promoting oxygen availability and decreasing oxygen consumption, the effect of which counteracts cellular hypoxia.Semenza, G.L. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu. Rev. Pathol. 2014, 9, 47–71. Therefore, kalkitoxin's HIF-1 inhibitory ability positions it as a potentially promising molecule to counteract the progression of some solid tumor cancers by blocking the tumor proliferative response to hypoxia.
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These long-term cells were demonstrated to be actively cycling, as demonstrated by incorporation and release of BrdU. Since these cells were cycling but continued to contain the BrdU label in their DNA, the researchers reasoned that they must be segregating their DNA using an immortal DNA strand mechanism. Joshua Merok et al. from the lab of James Sherley engineered mammalian cells with an inducible p53 gene that controls asymmetric divisions.
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This increases the reaction rate of many of the steps in the cycle, and therefore increases flux throughout the pathway. Transcriptional regulation. Recent work has demonstrated an important link between intermediates of the citric acid cycle and the regulation of hypoxia-inducible factors (HIF). HIF plays a role in the regulation of oxygen homeostasis, and is a transcription factor that targets angiogenesis, vascular remodeling, glucose utilization, iron transport and apoptosis.
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Virus inhibitory protein, endoplasmic reticulum-associated, interferon- inducible (Viperin), also known as RSAD2 (radical SAM domain-containing 2), is a protein that is encoded by the RSAD2 gene. Viperin is a multifunctional protein in viral processes that is an interferon stimulated gene. It has been reported that viperin could be induced by either IFN-dependent or IFN- independent pathways and certain viruses may use viperin to increase their infectivity.
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Suppressor of cytokine signaling 5 is a protein that in humans is encoded by the SOCS5 gene. The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling.
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Boman was awarded the Fernström Prize for outstanding work in medicine in 2000. The Nordic scientific community mourned his loss in 2008, both with a posthumous acknowledgement of his lifetime's achievements in 2009, and by hosting the “Hans G. Boman” symposium held by Stockholm University on the 10-year anniversary of his death. In 2015, a family of immune-inducible peptides in Drosophila was named the "Bomanins" in Boman's honour.
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For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene. The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.
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HIG1 domain family member 1A (HIGD1A), also known as hypoglycemia/hypoxia inducible mitochondrial protein1-a (HIMP1-a) and hypoxia induced gene 1 (HIG1), is a protein that in humans is encoded by the HIGD1A gene on chromosome 3. This protein promotes mitochondrial homeostasis and survival of cells under stress and is involved in inflammatory and hypoxia-related diseases, including atherosclerosis, ischemic heart disease, and Alzheimer’s disease, as well as cancer.
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The cellular hypoxia response has been reported in a single study to be the main driver of DUX4-induced muscle cell death. The hypoxia-inducible factors (HIFs) are upregulated by DUX4, possibly causing pathologic signaling leading to cell death. Another study found that DUX4 expression in muscle cells led to the recruitment and alteration of fibrous/fat progenitor cells, which helps explain why muscles become replaced by fat and fibrous tissue.
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A yeast commonly used for protein production is Pichia pastoris. Examples of yeast expression vector in Pichia are the pPIC series of vectors, and these vectors use the AOX1 promoter which is inducible with methanol. The plasmids may contain elements for insertion of foreign DNA into the yeast genome and signal sequence for the secretion of expressed protein. Proteins with disulphide bonds and glycosylation can be efficiently produced in yeast.
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Gamma-interferon-inducible lysosomal thiol reductase is an enzyme that, in humans, is encoded by the IFI30 gene. The protein encoded by this gene is a lysosomal thiol reductase that at low pH can reduce protein disulfide bonds. The enzyme is expressed constitutively in antigen-presenting cells and induced by gamma-interferon in other cell types. This enzyme has an important role in MHC class II-restricted antigen processing.
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AIFM2 has been implicated in tumorigenesis as a p53-inducible gene. AIFM2 mRNA levels are observed to be downregulated in many human cancer tissues, though a previous study reported that AIFM2 mRNA transcripts were only detected in colon cancer and B-cell lymphoma cell lines. Furthermore, its DNA-binding ability contributes to its involvement in the apoptosis-inducing response to viral and bacterial infections, possibly through its role in ROS regulation.
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Fermitin family homolog 2 (FERMT2) also known as pleckstrin homology domain- containing family C member 1 (PLEKHC1) or kindlin-2 is a protein that in humans is encoded by the FERMT2 gene. Kindlin-2 is the first of the kindlin protein to be discovered in 1994. It was detected in a screen for epidermal growth factor (EGF)-induced mRNAs and initially named mitogen-inducible gene 2 (Mig-2) protein.
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Most of the compounds stabilize the hypoxia-inducible transcription factors which activate the EPO gene. The compounds include oxo-glutarate competitors, but also simple ions such as cobalt(II) chloride. Inhalation of a xenon/oxygen mixture activates production of the transcription factor HIF-1-alpha, which leads to increased production of erythropoietin and improved performance. It has been used for this purpose in Russia since at least 2004.
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Clinically observed prolyl hydroxylase domain mutations, as in the case of erythrocytosis- and breast cancer-associated PHD2 mutations, affect its selectivity for its HIF substrate, which has important implication for drug design. In humans, there are three isoforms of hypoxia-inducible factor- proline dioxygenase. These are PHD1, PHD2 and PHD3. PHD2, in particular, was identified as the most important human oxygen sensors due to its slow reaction with oxygen.
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Microbes trigger development of isolated lymphoid follicles in the small intestine of humans and mice, which are sites of mucosal immune response. Isolated lymphoid follicles (ILFs) collect antigens through M cells, develop germinal centers, and contain many B cells. Gram-negative commensal bacteria trigger the development of inducible lymphoid follicles by releasing peptidogylcans containing diaminopimelic acid during cell division. The peptidoglycans bind to the NOD1 receptor on intestinal epithelial cells.
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Since the identification of miR-138, a number of targets have been found and some of them have been verified experimentally. It has been proven that miR-138 is involved in different pathways. Furthermore, it is in relation with various types of cancer. ;HIF-1a: Hypoxia-inducible factor-1alpha (HIF-1a), one of the key regulators in cancer cells, has been shown to be one target of miR-138.
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As prolyl hydroxylase requires ascorbate as a cofactor to function, its absence compromises the enzyme’s activity. The resulting decreased hydroxylation leads to the disease condition known as scurvy. Since stability of collagen is compromised in scurvy patients, symptoms include weakening of blood vessels causing purpura, petechiae, and gingival bleeding. Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond physiologically to decreases in oxygen.
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PMID 12954431 Champagne F, Diorio J, Sharma S, Meaney MJ (2001) Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences USA 98(22):12736-41. PMID 11606726 Champagne F, Meaney MJ (2001) Like mother, like daughter: evidence for non-genomic transmission of parental behavior and stress responsivity. Progress in Brain Research 133:287-302.
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Apoptosis induction appears to be regulated by the hypoxia inducible factor 1α (HIF-1α) pathway. The RAS-transformed cell lines MDFB6 and B6ras show near complete loss of TSP-1 expression. Activation of CD47 with TSP-1 results in loss of viability in these RAS-expressing cells. Affected cells do not exhibit hallmarks of apoptosis but rather autophagy as seen by staining with acridine orange and immunoreactivity for LC3.
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CYP24A1 is expressed in tissues which are considered targets for vitamin D, including kidney, intestine and bone. Transcription of the CYP24A1 gene is markedly inducible by 1,25-(OH)2D3 binding to the vitamin D receptor. The gene has a strong, positive vitamin D response element in the promoter. Through regulation of CYP24A1 expression, a negative feedback control system is created to limit the effects of 1,25-(OH)2D3.
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The WNK1 mutant found in FHHt harbors a large deletion within intron 1 that causes an increase in the expression of full length WNK1. The boost in WNK1 leads to increases in NCC activation that promotes the high blood pressure/hypertension associated with FHHt. WNK1 activates the serum-and glucocorticoid-inducible protein kinase SGK1, leading to increased expression of the epithelial sodium channel (ENaC), which also promotes sodium re absorption.
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Epigenetic editing using an inducible mechanism offers a wide array of potential use to study epigenetic effects in various states. One research group employed an optogenetic two- hybrid system which integrated the sequence specific TALE DNA-binding domain with a light-sensitive cryptochrome 2 protein (CIB1). Once expressed in the cells, the system was able to inducibly edit histone modifications and determine their function in a specific context.
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PFKFB3 expression is induced by hypoxia. The promoter of PFKFB3 contains binding sites, called hypoxia response elements (HREs), that recruit the binding of hypoxia- inducible factor-1 (HIF-1). Hypoxia signaling via HIF-1α stabilization upregulates the transcription of genes that permit survival in low oxygen conditions. These genes include glycolysis enzymes, like PFKFB3, that permit ATP synthesis without oxygen, and vascular endothelial growth factor (VEGF), which promotes angiogenesis.
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Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 (this enzyme) belong to the heme oxygenase family.
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The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene.
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Conditional/inducible mutation approaches are then required that first allow the mouse to develop and mature normally prior to ablation of the gene of interest. Another serious limitation is a lack of evolutive adaptations in knockout model that might occur in wild type animals after they naturally mutate. For instance, erythrocyte-specific coexpression of GLUT1 with stomatin constitutes a compensatory mechanism in mammals that are unable to synthesize vitamin C.
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LOX expression is regulated by hypoxia-inducible factors (HIFs), and, hence, LOX expression is often upregulated in hypoxic breast and head and neck tumors. Patients with high LOX-expressing tumors have poor overall survival. Furthermore, inhibition of LOX has been demonstrated to eliminate metastases in mice. Secreted LOX is responsible for the invasive properties of hypoxic cancer cells through focal adhesion kinase activity and cell-to-matrix adhesion.
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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.
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The C22orf31 promoter has many transcription factor binding sites. C22orf31's transcription factors are commonly found in immortalized liver cancer cell lines (HepG2) and immortalized myelogenous leukemia cell lines (K562). The presence of C/EBP epsilon suggests a role for C22orf31 in myeloid cell differentiation. The presence of ARNT, which is typically associated with hypoxia-inducible factor 1 alpha, suggests a role for C22orf31 in the formation of acute myeloblastic leukemia.
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Several popular inducible promoters in E. coli are the pBad, pTet, and pLac promoters, all of which repress gene expression by a repressor molecule that binds the gene operator and blocks RNAP progression. Progress in engineering Synechocystis sp. PCC6803 is currently hampered by promoter issues. As noted above in RNA Polymerase and Sigma Factors, the beta clamp proteins within the RNAP complex have a higher initial binding affinity in Synechocystis sp.
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A dinitrosyl iron complex (DNIC), the product from the immune responsive attack of NO on Fe-S proteins.Nitric oxide is generated by phagocytes (monocytes, macrophages, and neutrophils) as part of the human immune response. Phagocytes are armed with inducible nitric oxide synthase (iNOS), which is activated by interferon-gamma (IFN-γ) as a single signal or by tumor necrosis factor (TNF) along with a second signal.Gorczyniski and Stanely, Clinical Immunology.
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Several variants of CRISPR-Cas9 allow gene activation or genome editing with an external trigger such as light or small molecules. These include photoactivatable CRISPR systems developed by fusing light-responsive protein partners with an activator domain and a dCas9 for gene activation, or by fusing similar light-responsive domains with two constructs of split-Cas9, or by incorporating caged unnatural amino acids into Cas9, or by modifying the guide RNAs with photocleavable complements for genome editing. Methods to control genome editing with small molecules include an allosteric Cas9, with no detectable background editing, that will activate binding and cleavage upon the addition of 4-hydroxytamoxifen (4-HT), 4-HT responsive intein-linked Cas9, or a Cas9 that is 4-HT responsive when fused to four ERT2 domains. Intein-inducible split-Cas9 allows dimerization of Cas9 fragments and rapamycin-inducible split-Cas9 system developed by fusing two constructs of split-Cas9 with FRB and FKBP fragments.
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Further, these knockouts can be inducible. In several mouse studies, tamoxifen is used to induce the Cre recombinase. In this case, Cre recombinase is fused to a portion of the mouse estrogen receptor (ER) which contains a mutation within its ligand binding domain (LBD). The mutation renders the receptor inactive, which leads to incorrect localization through its interactions with chaperone proteins such as heat shock protein 70 and 90 (Hsp70 and Hsp90).
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In E. coli, the lacZ gene is the structural gene for β-galactosidase; which is present as part of the inducible system lac operon which is activated in the presence of lactose when glucose level is low. β-galactosidase synthesis stops when glucose levels are sufficient. Beta- galactosidase has many homologues based on similar sequences. A few are evolved beta-galactosidase (EBG), beta-glucosidase, 6-phospho-beta- galactosidase, beta-mannosidase, and lactase-phlorizin hydrolase.
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Cytochrome P450 A2 is usually not inducible by clinically frequently used drugs making it ideal even in complex clinical situations (exceptions are oral contraceptives resulting in a strong induction of P450 A2). Nutrition and lifestyle can strongly influence P450 A2 induction e.g. smoking or coffee consumption.Tantcheva-Poor, I. and Zaigler, M. and Rietbrock, S. and Fuhr, U. Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test.
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Interferon alpha-inducible protein 6 is a protein that in humans is encoded by the IFI6 gene. This gene was first identified as one of the many genes induced by interferon. The encoded protein may play a critical role in the regulation of apoptosis. A mini-satellite that consists of 26 repeats of a 12 nucleotide repeating element resembling the mammalian splice donor consensus sequence begins near the end of the second exon.
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Plants showing inducible CAM and CAM-cycling are typically found in conditions where periods of water shortage alternate with periods when water is freely available. Periodic drought – a feature of semi-arid regions – is one cause of water shortage. Plants which grow on trees or rocks (as epiphytes or lithophytes) also experience variations in water availability. Salinity, high light levels and nutrient availability are other factors which have been shown to induce CAM.
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In molecular biology, cyanase (, also known as cyanate hydratase or cyanate lyase) is an enzyme which catalyses the bicarbonate dependent metabolism of cyanate to produce ammonia and carbon dioxide. The systematic name of this enzyme is carbamate hydrolyase. In E. coli, cyanase is an inducible enzyme and is encoded for by the cynS gene. Cyanate is a toxic anion, and cyanase catalyzes the metabolism into the benign products of carbon dioxide and ammonia.
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GrpE (Gro-P like protein E) is a bacterial nucleotide exchange factor that is important for regulation of protein folding machinery, as well as the heat shock response.Delaney JM. A grpE mutant of Escherichia coli is more resistant to heat than the wild-type. J Gen Microbiol. 1990;136(5):797-801. doi:10.1099/00221287-136-5-797 It is a heat-inducible protein and during stress it prevents unfolded proteins from accumulating in the cytoplasm.
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These eukaryotic nucleotide exchange factors are all heat-shock inducible meaning that they serve a similar function as GrpE, to protect the cell from unfolded protein aggregation. These nucleotide exchange factors always interact with subdomain IIB of the nucleotide binding cleft of their respective heat-shock proteins. The binding of the nucleotide exchange factor to a nucleotide binding cleft and the shift to an open conformation is conserved between prokaryotes and eukaryotes.
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Interferon-induced transmembrane protein 1 is a protein that in humans is encoded by the IFITM1 gene. IFITM1 has also recently been designated CD225 (cluster of differentiation 225). This protein has several additional names: fragilis (human homolog of the mouse protein), IFI17 [interferon-induced protein 17], 9-27 [Interferon-inducible protein 9-27] and Leu13. IFITM1 is a member of the IFITM family (Interferon-induced transmembrane protein) which is encoded by IFITM genes.
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Suppressor of cytokine signaling 6 is a protein that in humans is encoded by the SOCS6 gene. The protein encoded by this gene contains a SH2 domain and a CIS homolog domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI) protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling.
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Experiments in rats have examined, in fine detail, the course of testicular events during a bacterial infection. In the short term (3 hours) multiple inflammatory factors are produced and released by testicular macrophages. Examples are prostaglandin E2, inducible nitric oxide synthase (iNOS), TNFα and IL-1β, although at lower levels than other tissues. Non-immune cells of the testis such as Sertoli cells and Leydig cells also able to respond to bacteria.
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Many of these compounds were found to be hepatotoxic to various degree and tolerance to the anti-inflammatory effect developed within weeks. An alternative approach is to evaluate the potential for targeting upstream MAPKs, such as ASK1. Studies in animal models of inflammatory arthritis have yielded promising results, and ASK1 has recently been found to be unique amongst the MAPKs in that it is inducible by inflammatory cytokines such as TNF-α.
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Phlorotannin production strategy may be constitutive or inducible. As studies demonstrated that herbivory can induce phlorotannin production, it has been suggested that they may have a role in algae defense. However, results form other studies suggest that the deterrent role of phlorotannins on herbivory is highly dependent on both algae and herbivore species. In Fucus vesiculosus, it is galactolipids, rather than phlorotannins, that act as herbivore deterrents against the sea urchin Arbacia punctulata.
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In adult stem cells, p53 regulation is important for maintenance of stemness in adult stem cell niches. Mechanical signals such as hypoxia affect levels of p53 in these niche cells through the hypoxia inducible factors, HIF-1α and HIF-2α. While HIF-1α stabilizes p53, HIF-2α suppresses it. Suppression of p53 plays important roles in cancer stem cell phenotype, induced pluripotent stem cells and other stem cell roles and behaviors, such as blastema formation.
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More than half of the C2H2-ZNF genes are associated with a KRAB domain in the human genome. They are more prone to clustering and are found in large clusters on the human genome. The KRAB domain presents one of the strongest repressors in the human genome. Once the KRAB domain was fused to the tetracycline repressor (TetR), the TetR-KRAB fusion proteins were the first engineered drug-inducible repressor that worked in mammalian cells.
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These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 (inducible) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general).
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PARP1 is required for NF-κB transcription of proinflammatory mediators such as tumor necrosis factor, interleukin 6, and inducible nitric oxide synthase. PARP1 activity contributes to the proinflammatory macrophages that increase with age in many tissues. ADP-riboyslation of the HMGB1 high-mobility group protein by PARP1 inhibits removal of apoptotic cells, thereby sustaining inflammation. In asthma PARP1 facilitates recruitment and function of immune cells, including CD4+ T-cells, eosinophils, and dendritic cells.
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Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene. Pentraxin 3 (ptx3) is a member of the pentraxin superfamily. This super family characterized by cyclic multimeric structure. PTX3 is rapidly produced and released by several cell types, in particular by mononuclear phagocytes, dendritic cells (DCs), fibroblasts and endothelial cells in response to primary inflammatory signals [e.g.
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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.
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Recent studies reveal that multiple AGC kinases, except for PHOT1 and PHOT2, are involved in plant phototropism. Firstly, PINOID, exhibiting a light-inducible expression pattern, determines the subcellular relocation of PIN3 during phototropic responses via a direct phosphorylation. Secondly, D6PK and its D6PKL homologs modulates the auxin transport activity of PIN3, likely through phosphorylation as well. Third, upstream of D6PK/D6PKLs, PDK1.1 and PDK1.2 acts an essential activator for these AGC kinases.
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ADAR1 is one of multiple genes which can contribute to Aicardi–Goutières syndrome when mutated. This is a genetic inflammatory disease primarily affecting the skin and the brain. The inflammation is caused by incorrect activation of interferon inducible genes such as those activated to fight off viral infections. Mutation and loss of function of ADAR1 prevents destabilization of double stranded RNA (dsRNA) and the body mistakes this for viral RNA resulting in an autoimmune response.
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Suppressor of cytokine signaling 2 is a protein that in humans is encoded by the SOCS2 gene. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10 and interferon-gamma (IFN- gamma).
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Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma. GADD45G is involved in several different processes, including sexual development, human-specific brain development, tumor suppression, and the cellular stress response. GADD45G interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence.
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In addition to the process of protein folding, transport and degradation, this Hsp70 member can preserve the function of mutant proteins. Nonetheless, effects of these mutations can still manifest when Hsp70 chaperones are overwhelmed during stress conditions. Furthermore, this protein enhances antigen-specific tumor immunity by facilitating more efficient antigen presentation to cytotoxic T cells. Though it shares close homology to HSPA1A and HSPA1B, it is regulated differently and is not heat-inducible.
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Before mercury can be methylated, it must be transported into the cell through the lipid membrane. Mercury ions are bound by a mercury scavenger protein, MerP. MerP transfers the mercury ion to a cytoplasmic membrane transporter, MerT, then to the active site of mercuric reductase or mercury(II) reductase in the cytoplasm. Normally mercury would be toxic to the cell, but some microorganisms are resistant to mercury ion due to an inducible mer operon.
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The VHL (Von Hippel–Lindau) gene encodes a component of an E3 Ubiquitin Ligase. VHL complex targets member of the hypoxia-inducible transcription factor family (HIF) for degradation by interacting with the oxygen-dependent destruction domain under normoxic condition. HIF activates downstream targets such as the vascular endothelial growth factor (VEGF), promoting angiogenesis. Mutations in VHL prevent degradation of HIF and thus lead to the formation of hypervascular lesions and renal tumors.
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Not only do transcription factors act downstream of signaling cascades related to biological stimuli but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF), which upregulates genes necessary for survival at higher temperatures, hypoxia inducible factor (HIF), which upregulates genes necessary for cell survival in low-oxygen environments, and sterol regulatory element binding protein (SREBP), which helps maintain proper lipid levels in the cell.
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Overexpression of HK3 has resulted in increased ATP levels, decreased reactive oxygen species (ROS) production, attenuated reduction in the mitochondrial membrane potential, and enhanced mitochondrial biogenesis. Overall, HK3 may promote cell survival by controlling ROS levels and boosting energy production. Currently, only hypoxia is known to induce HK3 expression through a HIF-dependent pathway. The inducible expression of HK3 indicates its adaptive role in metabolic responses to changes in the cellular environment.
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A novel class of compounds has been found to stimulate melanogenesis in a mechanism that is independent from α-melanocyte-stimulating hormone (α-MSH) activation of the melanocortin 1 receptor (MC1 receptor). This is accomplished via small molecule inhibition of salt-inducible kinases (SIK). Inhibition of SIK increases transcription of MITF which is known to increase melanin production. Work published in June 2017 has demonstrated compounds that have efficacy when applied topically to human skin.
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The human HIF1A gene encodes for the alpha subunit, HIF1A of the transcription factor hypoxia-inducible factor (HIF1) . Its protein expression level can be measured by antibodies against HIF-1-alpha through various biological detection methods including western blot or immunostaining. HIF1A expression level is dependent on its GC-rich promoter activation. In most cells, HIF1A gene is constitutively expressed in low levels under normoxic conditions, however, under hypoxia, HIF1A transcription is often significantly upregulated.
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In addition, gene gating is orchestrated by two protein complexes, Spt-Ada-Gcn5-acetyltransferase (SAGA) and transcription–export complex 2 (TREX-2 complex). SAGA is a chromatin remodeling complex responsible for activating the transcription of certain inducible genes. The SAGA complex binds to gene promoters and also interacts with the TREX-2 complex. In turn, the TREX-2 complex interacts with the NPC, thus favouring the relocation of actively transcribed genes to the periphery of the cell nucleus.
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Professor Sonia Rocha Sónia Maria Campos Soares da Rocha, usually referred to as Professor Sónia Rocha, is a Portuguese cell biologist who holds a personal chair in biochemistry at the University of Liverpool, where she is the head of the Department of Biochemistry. Rocha runs an active multidisciplinary cell signaling research group studying hypoxia, and focused around transcription factors such as Hypoxia-inducible factors and NF-κB. Her laboratory is currently based in the Institute of Integrative Biology.
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Acquired VanA- and VanB-type glycopeptide resistance in enterococci is due to synthesis of modified peptidoglycan precursors terminating in D-lactate. As opposed to VanA-type strains which are resistant to both vancomycin and teicoplanin, VanB-type strains remain teicoplanin susceptible. The vanY gene was necessary for synthesis of the vancomycin-inducible D,D-carboxypeptidase EC activity previously proposed to be responsible for glycopeptide resistance. However, this activity was not required for peptidoglycan synthesis in the presence of glycopeptides.
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A variety of molecular and biochemical approaches are used to determine the mechanism of constitutive and induced plant defenses responses against herbivory. Induced defenses include secondary metabolic products, as well as morphological and physiological changes. An advantage of inducible, as opposed to constitutive defenses, is that they are only produced when needed, and are therefore potentially less costly, especially when herbivory is variable. Modes of induced defence include systemic acquired resistance and plant- induced systemic resistance.
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The effects of abnormal caspase-9 levels or function impacts the clinical world. The impact caspase-9 has on the brain can lead to future work in inhibition through targeted therapy, specifically with diseases associated with the brain as this enzyme may take part in the developmental pathways of neuronal disorders. The introduction of caspases may also have medical benefits. In the context of graft versus host disease, caspase-9 can be introduced as an inducible switch.
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Cell surface transmembrane glycoprotein CD200 receptor 1 is a protein that in humans is encoded by the CD200R1 gene. CD200R1 is expressed on the surface of myeloid cells and CD4+ T cells. It interacts with CD200 transmembrane glycoprotein that can be expressed on variety of cells including neurons, epithelial cells, endothelial cells, fibroblasts, and lymphoid cells. CD200R1 activation regulates the expression of pro-inflammatory molecules such as tumor necrosis factor (TNF-alpha), interferons, and inducible nitric oxide synthase (iNOS).
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When oxygen levels in the cell are low, it will limit its energy expenditure through the inhibition of protein synthesis. Under hypoxic conditions, hypoxia inducible factor one alpha (HIF1A) will stabilize and activate transcription of REDD1, also known as DDIT4. After translation, this REDD1 protein will bind to TSC2, which prevents 14-3-3 from inhibiting the TSC complex. Thus, TSC retains its GAP activity towards Rheb, causing Rheb to remain bound to GDP and mTORC1 to be inactive.
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Mouse models of SHANK3 include N-terminal knock-outs and a PDZ domain knock-out all of which also show social interaction deficits and variable other phenotypes. Most of these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous. In an inducible knockout, restoration of Shank3 expression in adult mice promoted dendritic spine growth and recovered normal grooming behaviour and voluntary social interaction. However, the reduced locomotion, anxiety and rotarod deficits remained.
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The Retinoic Acid-Inducible orphan G-protein-coupled receptors (RAIG) are a group of four closely related G protein-coupled receptors whose expression is induced by retinoic acid. The exact function of these proteins has not been determined but they may provide a mechanism by which retinoic acid can influence G protein signal transduction cascades. In addition, RAIG receptors interact with members of the frizzled class of G protein-coupled receptors and appear to activate the Wnt signaling pathway.
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The gene, HSP90AA1, encodes the human stress- inducible 90-kDa heat shock protein alpha (Hsp90A). Complemented by the constitutively expressed paralog Hsp90B which shares over 85% amino acid sequence identity, Hsp90A expression is initiated when a cell experiences proteotoxic stress. Once expressed Hsp90A dimers operate as molecular chaperones that bind and fold other proteins into their functional 3-dimensional structures. This molecular chaperoning ability of Hsp90A is driven by a cycle of structural rearrangements fueled by ATP hydrolysis.
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Interferon-induced GTP-binding protein Mx1 is a protein that in humans is encoded by the MX1 gene. In mice, the interferon-inducible Mx protein is responsible for a specific antiviral state against influenza virus infection. The protein encoded by this gene is similar to the mouse protein as determined by its antigenic relatedness, induction conditions, physicochemical properties, and amino acid analysis. This cytoplasmic protein is a member of both the dynamin family and the family of large GTPases.
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The expression of NDRG1 is regulated by hypoxia dependent and independent manner. Under hypoxia the oxygen sensor hypoxia-inducible factor (HIF)-1α is translocated from cytoplasma to nucleus, where binds to HIF-1β to form HIF-1 complex. This complex works as a transcription factor, binds to hypoxia response element (HRE) in the promoter of hypoxia-related genes, one of these genes is the NDGR1. Also heavy metal ions (nickel, cobalt, iron) upregulate NDRG1 by mimicking hypoxia.
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In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene. The enzyme has been identified in fetal liver, where it is posited to be the predominant ethanol-metabolizing enzyme, and may be connected to ethanol-mediated teratogenesis. In rats, within one day of birth the hepatic CYP2E1 gene is activated transcriptionally. CYP2E1 expression is easily inducible, and can occur in the presence of a number of its substrates, including ethanol, isoniazid, tobacco, isopropanol, benzene, toluene, and acetone.
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The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes.
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The PFKFB3 gene is mapped to single locus on chromosome 10 (10p15-p14). It spans a region of 32.5kb with an open reading frame that is 5,675bp long. It is estimated to consist of 19 exons, of which 15 are regularly expressed. Alternative splicing of the variable, COOH-terminal domain has been observed, leading to 6 different isoforms termed UBI2K1 to UBI2K6 in humans. Different nomenclature also recognizes two broad categories of PFKFB3 isoforms, termed ‘inducible’ and ‘ubiquitous’.
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Genetic regulatory circuits (also referred to as transcriptional regulatory circuits) are functional clusters of genes that impact each other's expression through inducible transcription factors and cis-regulatory elements. These circuits can be modeled in silico to predict the dynamics of a genetic system. Understanding of genetic regulatory circuits are key in the field of synthetic biology, where disparate genetic elements are combined to produce novel biological functions. Genetic regulatory circuits are analogous in many ways to electronic circuits.
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Similar to lens, cornea is a transparent, avascular tissue derived from the ectoderm that is responsible for focusing light onto the retina. However, unlike lens, cornea depends on the air-cell interface and its curvature for refraction. Early immunology studies have shown that BCP 54 comprises 20–40% of the total soluble protein in bovine cornea. Subsequent studies have indicated that BCP 54 is ALDH3, a tumor and xenobiotic-inducible cytosolic enzyme, found in human, rat, and other mammals.
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Phage λ gamma is necessary to inhibit E. coli nuclease activity and protect the transformed linear DNA in vivo. Following λ-red operon activity induction, a linear, double-stranded cassette encoding a selectable marker, such as antibiotic resistance, is transformed into the cells in place of the target gene and incorporated into the DNA behind a specific inducible promoter. This allows for growth selection of the recombinant cells with proper insertion location verified using polymerase chain reaction (PCR).
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Inducible Cre activation is achieved using CreER (estrogen receptor) variant, which is only activated after delivery of tamoxifen. This is done through the fusion of a mutated ligand binding domain of the estrogen receptor to the Cre recombinase, resulting in Cre becoming specifically activated by tamoxifen. In the absence of tamoxifen, CreER will result in the shuttling of the mutated recombinase into the cytoplasm. The protein will stay in this location in its inactivated state until tamoxifen is given.
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In keeping with its critical importance in maintaining life, GCL is subject to a multi-level regulation of its expression, function, and activity. GCL expression is regulated at the transcriptional (transcription of the GCLC and GCLM DNA to make mRNA), posttranscriptional (the stability of the mRNA over time), translational (processing of the mRNA into protein), and posttranslational levels (involving modifications to the existing proteins). Although baseline constitutive expression is required to maintain cell viability, expression of the GCL subunits is also inducible in response to oxidative stress, GSH depletion, and exposure to toxic chemicals, with the Nrf2, AP-1, and NF-κB transcription factors regulating the inducible and constitutive expression of both subunits In terms of enzyme functional regulation, GSH itself acts as a feedback inhibitor of GCL activity. Under normal physiologic substrate concentrations, the GCLC monomer alone may synthesize gamma-glutamylcysteine; however, the normal physiologic levels of GSH (estimated at around 5 mM) far exceeds the GSH Ki for GCLC, suggesting that only the GCL holoenzyme is functional under baseline conditions.
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Viral promoters are often used for constitutive expression in plasmids and in viral vectors because they normally force constant transcription in many cell lines and types reliably. Inducible expression depends on promoters that respond to the induction conditions: for example, the murine mammary tumor virus promoter only initiates transcription after dexamethasone application and the Drosophilia heat shock promoter only initiates after high temperatures. Some vectors are designed for transcription only, for example for in vitro mRNA production. These vectors are called transcription vectors.
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Growth arrest and DNA-damage-inducible proteins-interacting protein 1 is a protein that in humans is encoded by the GADD45GIP1 gene. GADD45GIP1, also known as CRIF1 is newly identified de novo components in large subunit of mitoribosome. It is essential for the translation of mitochondrial oxidative phosphorylation (OXPHOS) polypeptides in mammalian mitochondria. CRIF1 interacts with low-sulfur (LSU) proteins, some of which surround the exit tunnel of the mitoribosome, and also interacts with nascent OXPHOS polypeptides and the mitochondrial-specific chaperone Tid1.
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Recent data suggest that the BST-2 transmembrane domain is crucial for interference by Vpu. The interaction of Vpu and BST-2 results in the downregulation of BST-2 from the cell surface. BST-2, which is an interferon (IFN)-inducible cell surface protein, appears to “tether” HIV to the cell in the absence of Vpu. BST-2 is a heavily glycosylated 29- to 33-kDa integral membrane protein with both a transmembrane domain and a putative glycosylphosphatidylinositol anchor (GPI).
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It was found that an inducible colitis-associated glycome (CAG), which contains an immature (nonsialylated) core-1 O-glycan expressed by CD4+ T cells, was identified as a ligand of gal-4 under intestinal inflammatory conditions (Nishida et al., 2012). Thus, gal-4 may activate the PKCθ by binding to CAG and, then contributing to aggravation of colitis. In consistent with this, gal-4, which shows a high affinity to immature O-glycan (Ideo et al., 2002; Blixt et al.
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The plasmid may be integrated into the genome, resulting in a stable transfection, or may remain independent of the genome, called transient transfection. DNA coding for a protein of interest is now inside a cell, and the protein can now be expressed. A variety of systems, such as inducible promoters and specific cell-signaling factors, are available to help express the protein of interest at high levels. Large quantities of a protein can then be extracted from the bacterial or eukaryotic cell.
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In 1997, Hajime Tei, Yoshiyuki Sakaki, and Hitoshi Okamura discovered the mammalian period gene PER1 in mice and humans. They also discovered PER2, PER3, and the mammalian homolog of the Drosophila gene timeless. They found that Per1 is light-inducible and can phase shift the circadian clock by light. Okamura worked with Jay Dunlap, a chronobiologist specializing in circadian rhythms in Neurospora, to show that mammalian clocks are similar to neurospora clocks in their use of induction to phase shift.
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When the kinase activity of mTOR is activated, its downstream effectors, the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a) are increased. HIF-1a then stimulates VEGF. Whether or not mTOR kinase is activated, determines whether the tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis. mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes.
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This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), GM- CSF, and interferon-gamma (IFN-γ). The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling.
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There, he studied how immunoglobulin A (IgA) in plasma cells regulate the intestinal B cell response. IgA released by plasma cells is important for maintaining a first-line of defense against food-borne pathogens and toxins in the gut. Fritz discovered that tumor necrosis factor alpha and inducible nitric oxide synthase are required for IgA plasma cell homeostasis during healthy and infection conditions. From these results, he suggests that plasma cells should be re-examined for their roles in inflammation and infection.
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Due to the regulatory role of LPP3 in vascular and embryonic development, inactivation of this protein can contribute to cardiovascular disease and developmental complications. For example, inducible inactivation of LPP3 in both endothelial and hematopoietic cells leads to atherosclerosis due to accumulation of LPA in human plaques. Likewise, plasma LPA levels are significantly elevated in patients with acute coronary syndromes. It was further observed that reduced levels of endothelial LPP3 is associated with disturbed flow and mechano-regulation in blood vessels.
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The reason for this is unknown. Missense mutations in the active site of these IDH2 induce a neo-enzymatic reaction wherein NADPH reduces αKG to D-2-hydroxyglutarate, which accumulates and leads to the inhibition of hypoxia-inducible factor 1α (HIF1α) degradation (inhibition of the HIF prolyl-hydroxylase), as well as changes in epigenetics and extracellular matrix homeostasis. Such mutations also imply less NADPH production capacity. Tumors of various tissue types with IDH1/2 mutations show improved responses to radiation and chemotherapy.
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A significant number of people with hypertrophic cardiomyopathy do not have any symptoms and will have a normal life expectancy, although they should avoid particularly strenuous activities or competitive athletics. Asymptomatic people should be screened for risk factors for sudden cardiac death. In people with resting or inducible outflow obstructions, situations that will cause dehydration or vasodilation (such as the use of vasodilatory or diuretic blood pressure medications) should be avoided. Septal reduction therapy is not recommended in asymptomatic people.
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The Growth Arrest and DNA Damage inducible 45 (Gadd45) gene family plays a large role in the hippocampus. Gadd45 facilitates hippocampal long-term potentiation and enhances persisting memory for motor performance, aversive conditioning, and spatial navigation. Additionally, DNA methylation has been shown to be important for activity- dependent modulation of adult neurogenesis in the hippocampus, which is mediated by GADD45b. GADD45b seems to act as a sensor in mature neurons for environmental changes which it expresses through these methylation changes.
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Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the MYLIP gene. MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol regulation. The expression of IDOL is induced by the sterol- activated liver X receptor. Increased Degradation of LDL Receptor Protein (IDOL) is a ubiquitin ligase that ubiquinates LDL receptors in endosomes and directs the receptors to the lysosomal compartment for degradation.
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This gene is the human homolog of mouse BMP-2-inducible kinase. Bone morphogenic proteins (BMPs) play a key role in skeletal development and patterning. Expression of the mouse gene is increased during BMP-2 induced differentiation and the gene product is a putative serine/threonine protein kinase containing a nuclear localization signal. Therefore, the protein encoded by this human homolog is thought to be a protein kinase with a putative regulatory role in attenuating the program of osteoblast differentiation.
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The TP53-inducible glycolysis and apoptosis regulator (TIGAR) also known as fructose-2,6-bisphosphatase TIGAR is an enzyme that in humans is encoded by the C12orf5 gene. TIGAR is a recently discovered enzyme that primarily functions as a regulator of glucose breakdown in human cells. In addition to its role in controlling glucose degradation, TIGAR activity can allow a cell to carry out DNA repair, and the degradation of its own organelles. Finally, TIGAR can protect a cell from death.
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This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome.
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These transcription factors cause the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The upregulation of these inflammatory mediators by ethanol is also associated with an increase in caspase 3 activity and a corresponding increase in cell apoptosis. The exact mechanism by which various concentrations of ethanol either activates or inhibits TLR4/IL-1RI signaling is not currently known, though it may involve alterations in lipid raft clustering or cell adhesion complexes and actin cytoskeleton organization.
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Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, and bacteria. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3). iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. Evidence has been found for NO signaling in plants, but plant genomes are devoid of homologs to the superfamily which generates NO in other kingdoms.
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Three-dimensional model of NO. In humans, nitric oxide is produced from L-arginine by three enzymes called nitric oxide synthases (NOS): inducible (iNOS), endothelial (eNOS), and neuronal (nNOS). The latter two are constantly active in endothelial cells and neurons respectively, whereas iNOS' action can be induced in states like inflammation (for example, by cytokines). In inflammation, several cells use iNOS to produce NO, including eosinophils. As such, eNO (also known as FeNO "fractional exhaled nitric oxide") has been dubbed an inflammometer.
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Retinoic acid early inducible 1 (RAE-1) family of murine cell surface glycoproteins is composed of at least five members (RAE-1α-ε). Genes encoding these proteins are located on mouse chromosome 10. RAE-1 proteins are related to MHC class I, they are made up of external α1α2 domain which is linked to the cell membrane by the GPI anchor. They function as stress-induced ligands for NKG2D receptor and their expression is low or absent on normal cells.
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Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively. NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products, notably interferon-gamma (IFN-γ) and lipopolysaccharide (LPS). Reactive nitrogen species act together with reactive oxygen species (ROS) to damage cells, causing nitrosative stress. Therefore, these two species are often collectively referred to as ROS/RNS.
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After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel; this can allow more complex regulation: with, for example, a low constant activity provided by one enzyme but an inducible high activity from a second enzyme. Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps and could not be regulated to serve the needs of the cell.
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This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine. They self-administer cocaine at lower doses than control, but have a greater likelihood of relapse when the drug is withheld. ΔFosB increases the expression of AMPA receptor subunit GluR2 and also decreases expression of dynorphin, thereby enhancing sensitivity to reward.
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Both Potocki–Lupski and Smith–Magenis syndromes arise through a faulty non-allelic homologous recombination mechanism. Both appear to involve a 1.3-3.7Mb chromosome section in 17p11.2 that includes the retinoic acid inducible 1 (RAI1) gene. Other candidate genes have been identified within the duplicated section, including SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In mice of the subfamily Murinae, a 32-34cM region of chromosome 11 is syntenic to 17p11.2, meaning that they contain the same genes in the same order and orientation.
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Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties. Oleanolic acid was found to exhibit weak anti-HIV and weak anti- HCV activities in vitro, but more potent synthetic analogs are being investigated as potential drugs. An extremely potent synthetic triterpenoid analog of oleanolic acid was found in 2005, that is a powerful inhibitor of cellular inflammatory processes. They work by the induction by IFN-γ of inducible nitric oxide synthase (iNOS) and of cyclooxygenase 2 in mouse macrophages.
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Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction. In adrenocortical cells the trophic hormone ACTH induces expression of TIMP-1 and the increase in TIMP expression is also associated with decreased collagenase activity.
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Introduction of too many siRNA can result in nonspecific events due to activation of innate immune responses. Most evidence to date suggests that this is probably due to activation of the dsRNA sensor PKR, although retinoic acid-inducible gene I (RIG-I) may also be involved. The induction of cytokines via toll-like receptor 7 (TLR7) has also been described. Chemical modification of siRNA is employed to reduce in the activation of the innate immune response for gene function and therapeutic applications.
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DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant- negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, and has an important role in the cell's stress response.
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Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the immune system. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk.
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The HIF-1α internal ribosome entry site (IRES) is an RNA element present in the 5' UTR of the mRNA of HIF-1α that allows cap-independent translation. The HIF-1α internal ribosome entry site (IRES) allows translation to be maintained under hypoxic cell conditions that inhibit cap-dependent translation [1]. The hypoxia-inducible factor-1α protein (HIF-1α) is a subunit of the HIF-1 transcription factor, which induces transcription of several genes involved in the cellular response to hypoxia.
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Nuclear factor of activated T-cells 5, also known as NFAT5, is a human gene that encodes a transcription factor that regulates the expression of genes involved in the osmotic stress. The product of this gene is a member of the nuclear factors of activated T cells (NFAT) family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells.
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In molecular biology, the DinI-like protein family is a family of short proteins. The family includes DNA-damage-inducible protein I (DinI) and related proteins. The SOS response, a set of cellular phenomena exhibited by eubacteria, is initiated by various causes that include DNA damage-induced replication arrest, and is positively regulated by the co-protease activity of RecA. Escherichia coli DinI, a LexA-regulated SOS gene product, shuts off the initiation of the SOS response when overexpressed in vivo.
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Like AIM2, IFI16 (IFN-inducible protein 16) belongs to the PYHIN (pyrin and HIN domain-containing) family. IFI16 in humans, and IFI204, the mouse orthologue play an important role in regulating the production of IFN during both bacterial and viral infectons. In contrast to AIM2, IFI16 is a nuclear DNA sensor. Following interaction with viral DNAs, IFI16 was shown to recruit caspase-1 through interaction with ASC, resulting in cell death of CD4+ T cells in response to HIV infection.
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The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.
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VEGF-A production can be induced in cell that is not receiving enough oxygen. When a cell is deficient in oxygen, it produces HIF, hypoxia-inducible factor, a transcription factor. HIF stimulates the release of VEGF-A, among other functions (including modulation of erythropoiesis). Circulating VEGF-A then binds to VEGF receptors on endothelial cells, triggering a tyrosine kinase pathway leading to angiogenesis. The expression of angiopoietin-2 in the absence of VEGF leads to endothelial cell death and vascular regression.
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Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex that mediates the cellular response to oxygen availability in multi-cellular organisms, ranging from the simplest known animal Trichoplax adhaerens to humans. Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work. The group solved crystal structures of PHD2 \- one of the human prolyl hydroxylases - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs, the ankyrin repeat domain.
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A Theta-type plasmid has been characterized in Lactobacillus sakei in 2003. It is a potential basis for Low-Copy-Number vectors in Lactobacilli. Vectors for inducible gene expression in Lactobacillus sakei can be constructed. The key elements of these vectors are a regulatable promoter involved in the production of the bacteriocins sakacin A and sakacin P and the genes encoding the cognate histidine protein kinase and response regulator that are necessary to activate this promoter upon induction by a peptide pheromone.
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Heat shock proteins (HSPs) are a diverse class of molecular chaperones that assist in folding under stress. While originally identified in heat stress response (hence the name “heat shock”), inducible HSP expression is a consequence of all known stressors (pH, osmotic, temperature, energy depletion, ion concentration, etc.). Genetic stress, a result of deleterious mutations, also increases HSP expression. HSPs are ubiquitous across all domains of life (Bacteria, Archaea, and Eukarya) and have been found in every species for which they have been tested.
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In particular, HK2 is ubiquitously expressed in tissues, though it is majorly found in muscle and adipose tissue. In cardiac and skeletal muscle, HK2 can be found bound to both the mitochondrial and sarcoplasmic membrane. HK2 gene expression is regulated by a phosphatidylinositol 3-kinaselp70 S6 protein kinase-dependent pathway and can be induced by factors such as insulin, hypoxia, cold temperatures, and exercise. Its inducible expression indicates its adaptive role in metabolic responses to changes in the cellular environment.
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BHLHE41 is thought to be a critical regulator of the metastasis of triple- negative-breast cancer (TNBC). Regulated by the p63 metastasis suppressor, BHLHE41 inhibits TNBC through the inhibition of HIF-1α and hypoxia-inducible factor 2α (HIF-2α). Studies have shown that BHLHE41 is both required and sufficient to limit the expression of HIF-target genes, by mechanistically binding to HIFs and promoting proteasomal degradation. Breast cancer tumors that show high expression of BHLHE41 and CyclinG2 are believed to have a lower metastatic risk.
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No endogenous ligands of ERRα have been identified to date, hence ERRα is classified as an orphan receptor. In addition both biochemical and structural studies indicate that ERRα is constitutively active in the absence of ligand. ERRα does, however, interact with the metabolic-inducible coactivator PGC1-α in its AF2 region which is sometimes referred to as the "protein ligand" of ERRα. The isoflavone phytoestrogens genistein and daidzein are non-selective ERR agonists, while XCT790 has been identified as a potent and selective inverse agonist of ERRα.
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Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, or in vitro studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects.
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These cytokines also enhance the synthesis of intracellular I alpha T1 proteins and IL-1beta upregulated ulinastatin. Ulinastatin is implicated in downregulating or suppressing the production of proMMP-1 and proMMP, prostaglandin H2 synthase-2, urokinase, CXC chemokine, pro-inflammatory cytokines, inducible nitric oxide synthase, tissue factor, P-selectin, intercellular adhesion molecule-1, phosphorylation of the extracellular signal-regulated protein kinases, and NF-kappaB activation. Ulinastatin also suppresses neutrophil accumulation and activity. The genes and proteins regulated by ulinastatin are implicated in the inflammatory process.
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Thyroid hormone-inducible hepatic protein is a protein that in humans is encoded by the THRSP gene. The protein encoded by this gene is similar to the gene product of S14, a rat gene whose expression is limited to liver and adipose tissue and is controlled by nutritional and hormonal factors. This gene has been shown to be expressed in liver and adipocytes, particularly in lipomatous modules. It is also found to be expressed in lipogenic breast cancers, which suggests a role in controlling tumor lipid metabolism.
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A similar phenomenon is observed for the Jumonji C family of KDMs which require a hydroxylation to perform demethylation at the epsilon-amino methyl group. Additionally, the inability of prolyl hydroxylases to catalyze reactions results in stabilization of hypoxia-inducible factor alpha, which is necessary to promote degradation of the latter (as under conditions of low oxygen there will not be adequate substrate for hydroxylation). This results in a pseudohypoxic phenotype in the cancer cell that promotes angiogenesis, metabolic reprogramming, cell growth, and migration.
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DERA is part of the inducible deo operon in bacteria which allows for the conversion of exogenous deoxyribonucleosides for energy generation. The products of DERA, glyceraldehyde-3-phosphate and acetaldehyde (subsequently converted to acetyl CoA) can enter the glycolysis and Kreb’s cycle pathways respectively. In humans, DERA is mainly expressed in lungs, liver and colon and is necessary for the cellular stress response. After induction of oxidative stress or mitochondrial stress, DERA colocalizes with stress granules and associates with YBX1, a known stress granule protein.
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The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. At least three transcript variants encoding three different isoforms have been found for this gene.
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Mixing and matching the ligand-binding domains and DNA- binding domains of different hormone receptors can be used as an inducible expression mechanism to study the action of any gene with a hormone response element in its promoter. Selectively altering the ligand-binding domain to make it orthogonal to the natural ligand-receptor interface, as well as the making the DNA-binding domain and hormone response element orthogonal, would give a researcher precise control of a gene's transcription in order to study a gene's action.
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Monocytes/macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF1A) and consequently promotes glycolysis. HIF1A-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival.
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145-156, Shimono, Sugano, Nakayama, Jiang, Ono, et al. (2007) Rice WRKY45 Plays a Crucial Role in Benzothiadiazole-Inducible Blast Resistance. The Plant Cell Online. 19(6). 2064-2076, Zheng, Qamar, Chen and Mengiste (2006) Arabidopsis WRKY33 transcription factor is required for resistance to necrotrophic fungal pathogens. The Plant Journal. 48(4). 592-605 pathogens, as well as insect herbivory.Skibbe, Qu, Galis and Baldwin (2008) Induced Plant Defenses in the Natural Environment: Nicotiana attenuata WRKY3 and WRKY6 Coordinate Responses to Herbivory. Plant Cell. 20(7).
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In any case, the centromere difference is believed to play a major, although not exclusive, role in radiation sensitivity. It was suggested that possible molecular mechanisms responsible for the high radioresistance in Lepidoptera might include an inducible cell recovery system and a DNA repair probes. Lepidoptera also do not show the classical breakage-fusion-bridge cycle that is a characteristic of dominant lethals induced in Diptera. It appears that lepidopteran chromosomes can tolerate telomere loss without the drastic effects that this has on chromosomes in other orders.
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Immunohistochemistry is a technique that uses antibodies with fluorescent staining tags that target a specific antigen present in a certain protein. This high specificity allows us to localize the peptidergic and classical transmitter compounds, their synthetic enzymes and other cell specific antigen in neuronal tissiue. An example of the application of this technique in neuroscience is the immunolabeling of antigens like NGF-Inducible Large External glycoprotein (NILE-GF), choline acetyltransferase, parvalbumin, and neurofilament protein. All of these antigens are present in specific neuronal cell types.
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As opposed to the critical calcium-dependent regulation of constitutive NOS enzymes (nNOS and eNOS), iNOS has been described as calcium-insensitive, likely due to its tight non-covalent interaction with calmodulin (CaM) and Ca2+. The gene coding for iNOS is located on Chromosome 17. While evidence for ‘baseline’ iNOS expression has been elusive, IRF1 and NF-κB-dependent activation of the inducible NOS promoter supports an inflammation mediated stimulation of this transcript. iNOS produces large quantities of NO upon stimulation, such as by proinflammatory cytokines (e.g.
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Studies on transgenic mouse in vivo demonstrate that lung over-expression of IL-13 induces subepithelial airway fibrosis. IL-13 is the dominant effector in toxin, infection, allergic, and post-transplant bronchiolitis obliterans models of fibrosis. Other research suggests that IL-13 is responsible for the promotion of the survival and the migration of epithelial cells, production of inducible nitric oxide synthase by airway epithelial cells, activation of macrophages, permeability of the epithelial cells, and transformation of airway fibroblasts to myofibroblasts leading to collagen deposition.
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IRGs Have Evolved From Invertebrates Studies to determine the evolutionary origins of vertebrates have led to understanding the development of immune system processes and furthermore answer the questions of how and why pathogens have learned to evade and shut down these selectable genetic traits. Eight functional and four pseudo IRG genes have been identified in the invertebrate Branchiostoma floridiae. Li et al. determined expression patterns of functional IFN-inducible GTPase genes in Branchiostoma japonicum at various immunologic sites when induced by pathogens and pathogenic substances.
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Nitric oxide dioxygenase was discovered, and first reported in 1998, as an inducible O2-dependent enzymatic activity that protected bacteria against nitric oxide toxicity. The enzyme was identified with the E. coli flavohemoglobin. More recently, another protein has been identified as a NO dioxygenase - rhodobacter sphaeroides haem protein (SHP), a novel cytochrome with NO dioxygenase activity. Although the biological function of SHP has yet to be identified, SHP has been shown, that with oxygen bound, it can react rapidly with nitric oxide to form nitrate.
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Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, or in vitro studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects.
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Myocilin is believed to have a role in cytoskeletal function. MYOC is expressed in many ocular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. Scientific research has found the function of myocilin to be linked with other proteins, making it part of a protein complex.
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The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes.
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The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes.
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The gene PSMB6 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic inducible subunit beta1i (proteasome beta 9 subunit). The proteasomes are an pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Compromised proteasome complex assembly leads to reduced proteolytic activities and accumulation of damaged or misfolded protein species.
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Some flowers will change color at the same rate regardless of pollinator visitation, while others can be induced by pollen deposition on the stigma. However, inducible flowers will eventually change color due to senescence even without pollinator activity. Depending on the species, floral color change can affect an entire flower or it can occur in localized parts. Previous research has found that moth-pollinated flowers are more likely to have whole flower color changes, while other insect-pollinated flowers are more likely to have localized color changes.
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Because of its very large number of roles in the cell, manipulating the ubiquitin system represents an efficient way for such viruses to block, subvert or redirect critical host cell processes to support their own replication. The retinoic acid-inducible gene I (RIG-I) protein is a primary immune system sensor for viral and other invasive RNA in human cells. The RIG- I-like receptor (RLR) immune signaling pathway is one of the most extensively studied in terms of the role of ubiquitin in immune regulation.
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Protein BTG2 also known as BTG family member 2 or NGF-inducible anti- proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the BTG2 gene ( _B_ -cell _t_ ranslocation _g_ ene _2_ ) and in other mammals by the homologous Btg2 gene. This protein controls cell cycle progression and proneural genes expression by acting as a transcription coregulator that enhances or inhibits the activity of transcription factors. The protein BTG2 is the human homolog of the PC3 ( _p_ heochromocytoma _c_ ell _3_ ) protein in rat and of the Tis21 ( _t_ etradecanoyl phorbol acetate- _i_ nducible _s_ equence _21_ ) protein in mouse. Tis21 had been originally isolated as a sequence induced by TPA in mouse fibroblasts, whereas PC3 was originally isolated as sequence induced at the beginning of neuron differentiation; BTG2 was then isolated in human cells as sequence induced by p53 and DNA damage. The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2).
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Within Mammals, both PAS domains play important roles. PAS A is responsible for the protein-protein interactions with other PAS domain proteins, while PAS B has a more versatile role. It mediates interactions with chaperonins and other small molecules like dioxin, but PAS B domains in NPAS2, a homolog of the Drosophila clk gene, and the hypoxia inducible factor (HIF) also help to mediate ligand binding. Furthermore, PAS domains containing the NPAS2 protein have been shown to be a substitute for the Clock gene in mutant mice who lack the Clock gene completely.
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Expression of C16orf96 when different hypoxia-inducible factors are reduced C16orf96 expression is generally low in cells. in situ hybridization experiments suggest that C16orf96 RNA is only expressed in the testis while the EST profile for C16orf96 shows gene expression is low in testis and skin only.The Human Protein Atlas of C16orf96EST profile Hs.684212 Expression of the C16orf96 gene is modulated by the depletion of both hypoxia induced factor 1/2α (HIF1/2α). When only one of the factors is depleted expression does not change suggesting that there is redundancy with these two HIF.
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Mouse models having two transgenes are called bi transgenic. To check the cooperation of two oncogenes, Tim Stewert and group made the first bi-transgenic mouse models in 1987, MMTV-Myc and MMTV- Ras mice were crossed with a resulting acceleration in tumorigenesis. Expression of TGFβ in the breast cancer cells of MMTV-ErbB2; MMTV-TGFβ double-transgenic mice can induce higher levels of circulating tumor cells and lung metastasis. Ras gene can be combined with rtTA (reverse tetracycline transactivator) to generate bi-transgenic inducible mouse model through tetracycline-controlled transcriptional activation e.g.
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Evidence from pre-clinical and clinical investigations has revealed the involvement of CXCR3 and its ligands in several cardiovascular diseases (CVDs) of diverse etiologies including atherosclerosis, hypertension, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, cardiac hypertrophy and heart failure, as well as in heart transplant rejection and transplant coronary artery disease (CAD). CXCL9-10-11 have been recognized to be valid biomarkers for the development of heart failure and left ventricular dysfunction in two pilot studies, suggesting an underlining correlation between levels of the interferon (IFN)-γ-inducible chemokines and the development of adverse cardiac remodeling.
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Zhang, et al., also report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components. Multiple methods of direct transformation of somatic cells into induced neural stem cells have been described. Proof of principle experiments demonstrate that it is possible to convert transplanted human fibroblasts and human astrocytes directly in the brain that are engineered to express inducible forms of neural reprogramming genes, into neurons, when reprogramming genes (Ascl1, Brn2a and Myt1l) are activated after transplantation using a drug.
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Sankar Ghosh is an Indian immunologist and microbiologist, who is the chair of the Department of Microbiology & Immunology at Columbia University Medical Center. Immunologist and Microbiologist Sankar Ghosh, Ph.D., to Head Department of Microbiology at Columbia University Medical Center Columbia University Medical Center website. Previously he has remained a Professor of Immunobiology, Molecular biophysics and Biochemistry, and Molecular, Cellular & Developmental biology, and researcher working at Yale University for 17 years. Sankar Ghosh's particular area of research is focused on the activation of cellular responses via the inducible transcription factor, NF-κB.
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Abortive HIV infection occurs due to slowing of reverse transcription promoting cytosolic DNA accumulation. This viral DNA is sensed by gamma-interferon-inducible protein 16 (IFI16), which produces an innate immune response against the virus by activating caspase 1 in IFI16 inflammasomes and inducing pyroptosis, a highly inflammatory form of programmed cell death. These findings cast CD4 T-cell death during HIV infection in a different light. Rather than the virus playing a major role, it is the host response to viral DNA produced during abortive infection that triggers CD4 T-cell death.
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Growth hormone-inducible transmembrane protein (GHITM), also known as transmembrane BAX inhibitor motif containing protein 5 (TMBIM5), is a protein that in humans is encoded by the GHITM gene on chromosome 10. It is a member of the BAX inhibitor motif containing (TMBIM) family and localizes to the inner mitochondrial membrane (IMM), as well as the endoplasmic reticulum (ER), where it plays a role in apoptosis through mediating mitochondrial morphology and cytochrome c release. Through its apoptotic function, GHITM may be involved in tumor metastasis and innate antiviral responses.
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The ability to differentiate into glial cells is repressed in neural stem cells with a neuronal cell fate. This repression is due largely to an irresponsiveness of neural stem cells towards astrocyte- inducing stimulations. The neural stem cells are non-responsive due to hypermethylated DNA in the promoter regions of astrocyte genes such as Gfap. The STAT3 binding site in the promoter region of Gfap is hypermethylated at E11.5 and barely so at E14.5, at which point it is able to receive astrocyte inducing stimulations and begin cytokine-inducible astrocyte differentiation.
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The tac promoter consists of the '-35' region of the trp promoter and the '-10' region of the lac promoter (and differs from the trc promoter by 1 bp). The tac promoter is, therefore, inducible by IPTG (Isopropyl β-D-1-thiogalactopyranoside), whilst also allowing higher maximum gene expression than either the lac or trp promoters. This makes it suitable for high-efficiency protein production of a recombinant protein. The strong repression of expression in the 'off' state is important since foreign proteins can be toxic to the host cell.
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NO is a major source of immunomodulation in rodents, and is produced by enzyme nitric oxide synthetase type 2 (NOS2) in the alveolar macrophage. NO inhibits tyrosine phosphorylation of the kinases involved in production of the interleukin-2 (IL-2) receptor, the expression of which is fundamental for T cell proliferation. In humans, however, NOS2 activity has been difficult to verify. There are two explanations for the lack of responsiveness in the promoter of human inducible nitric oxide synthetase (iNOS) to NO activation by lipopolysaccharides (LPS) + interferon gamma (IFNγ).
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Presence of oxygen or other small molecules can influence degron recognition. The von Hippel-Lindau (VHL) protein (substrate recognition part of a specific E3 ligase), for instance, recognizes the hypoxia-inducible factor alpha (HIF-α) only under normal oxygen conditions, when its proline is hydroxylated. Under hypoxia, on the other hand, HIF-a is not hydroxylated, evades ubiquitination and thus operates in the cell at higher concentrations which can initiate transcriptional response to hypoxia. Another example of small molecule control of protein degradation is phytohormone auxin in plants.
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Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart. There are three different classes of these enzymes in mammals: class 1 (low Km, cytosolic), class 2 (low Km, mitochondrial), and class 3 (high Km, such as those expressed in tumors, stomach, and cornea). In all three classes, constitutive and inducible forms exist. ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both are tetrameric enzymes composed of 54 kDa subunits.
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While TLR2 signaling can activate clearance of peptides, PSA induces an anti-inflammatory response when it binds to TLR2 on CD4+ T cells. Through TLR2 binding, PSA suppresses pro-inflammatory TH17 responses, promoting tolerance and establishing commensal gut colonization. Commensal gut microbes create a variety of metabolites that bind aryl hydrocarbon receptors (AHR). AHR is a ligand-inducible transcription factor found in immune and epithelial cells and binding of AHR is required for normal immune activation as the lack of AHR binding has been shown to cause over activation of immune cells.
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The C57BL/6 mouse has 23 IRG genes of which 21 may be functional in resistance to pathogens (6 are well characterized), whereas humans have evolved only 1 functional IRG gene (IRGM) and one pseudogene. Studies in mice have characterized the importance of the type 2 effector molecule IFNγ in various cell types and gone on to determine the importance of these proteins in intracellular pathogen resistance. Orthologous Irgc (aka: Cinema) genes are found in humans and mice. These orthologs are not IFN inducible and are expressed only in the testis of both mammals.
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On the other hand, representatives of standard microbiota induce only weak signals preventing inflammation. The mechanism of distinguishing between harmless and harmful bacteria on the molecular as well as on physiological levels is not completely understood. This process becomes much more intriguing when taking into account that commensals often share their surface molecules with pathogens. Epithelial cells are equipped with very sensitive recognition tools - toll like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) which recognize a broad variety of microbial structural components.
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Tet-ON inducible shRNA system An expression system is a system specifically designed for the production of a gene product of choice. This is normally a protein although may also be RNA, such as tRNA or a ribozyme. An expression system consists of a gene, normally encoded by DNA, and the molecular machinery required to transcribe the DNA into mRNA and translate the mRNA into protein using the reagents provided. In the broadest sense this includes every living cell but the term is more normally used to refer to expression as a laboratory tool.
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SMAD3 functions as a transcriptional modulator, binding the TRE (TPA responsive element) in the promoter region of many genes that are regulated by TGF-β. SMAD3 and SMAD4 can also form a complex with c-Fos and c-jun at the AP-1/SMAD site to regulate TGF-β-inducible transcription. The genes regulated by SMAD3-mediated TGFβ signaling affect differentiation, growth and death. TGF-β/SMAD signaling pathway has been shown to have a critical role in the expression of genes controlling differentiation of embryonic stem cells.
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The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases. The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs) and regulate expression of target genes containing LXR response elements.
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After the discovery of the lux operon, the use of bioluminescent bacteria as a laboratory tool is claimed to have revolutionized the area of environmental microbiology. The applications of bioluminescent bacteria include biosensors for detection of contaminants, measurement of pollutant toxicity and monitoring of genetically engineered bacteria released into the environment. Biosensors, created by placing a lux gene construct under the control of an inducible promoter, can be used to determine the concentration of specific pollutants. Biosensors are also able to distinguish between pollutants that are bioavailable and those that are inert and unavailable.
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Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene. This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.
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The Pho system is composed of various components including extracellular enzymes and transporters that are capable of phosphate assimilation in addition to extracting inorganic phosphate from organic sources. This is an essential process since phosphate plays an important role in cellular membranes, genetic expression, and metabolism within the cell. Under low nutrient availability, the Pho regulon helps the cell survive and thrive despite a depletion of phosphate within the environment. When this occurs, phosphate starvation-inducible (psi) genes activate other proteins that aid in the transport of inorganic phosphate.
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Several IFN-blocking strategies are currently being evaluated in clinical trials. For instance, a phase I clinical trial of the anti-IFN-α monoclonal antibody MEDI-545 in SLE patients suggested possible disease activity improvement in SLE patients. Another phase I clinical trial has reported a dose-dependent inhibition of IFN-α/β-inducible genes in both peripheral blood and skin biopsies in SLE patients treated with anti-IFN monoclonal antibody therapy. Also, some studies suggest that type I IFN in circulation may be useful to predict response to immunotherapy in RA.
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RIG-I (retinoic acid-inducible gene I) is a cytosolic pattern recognition receptor (PRR) responsible for the type-1 interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. These viruses can include West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses. RIG-I is structurally considered a helical ATP-dependent DExD/H box RNA helicase, that recognizes short viral double-stranded RNA (dsRNA) in the cytosol during a viral infection or other irregular RNAs (i.e.
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This particular subunit has been shown to interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. In addition, this subunit is involved in regulating hepatitis virus C internal ribosome entry site (IRES) activity, an activity essential for viral replication. This core alpha subunit is also involved in regulating the hypoxia-inducible factor-1alpha, a transcription factor important for cellular responses to oxygen tension. Recent study on underlying mechanisms of E3 ligase Parkin-related neurodegeneration identified this proteasome subunit as one of Parkin associating partner.
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Azoxymethane (AOM) is a genotoxic colonic carcinogen and is routinely used to induce colon tumours in mice. The AOM-induced tumours form in the last three centimeters of the distal colon but a p21 knock out mouse treated with AOM shows tumour distribution throughout the colon. AOM- induced tumours are characterized with mutations in the Apc gene. A novel inflammation-related mouse model of colorectal carcinogenesis combines AOM and dextran sodium sulphate (DSS) to induce colon lesions, positive for beta- catenin, COX-2 and inducible nitric oxide synthase.
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The Arntl gene was originally discovered in 1997 by two groups of researchers, John B. Hogenesch et al. in March under the name Mop3 and Ikeda and Nomura in April as part of a superfamily of PAS domain transcription factors. In 1998, Hogenesch's additional characterization of MOP3 revealed that its role as the partner of bHLH-PAS transcription factor CLOCK was essential to mammalian circadian clock function. The MOP3 protein, as it was originally known by the Hogenesch group, was found to dimerize with MOP4, CLOCK, and hypoxia-inducible factors.
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In addition to collagen, the mammalian proteins elastin and argonaute 2 have collagen-like domains in which hydroxyproline is formed. Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences. Hydroxylation of proline has been shown to be involved in targeting Hypoxia-inducible factor (HIF) alpha subunit (HIF-1 alpha) for degradation by proteolysis. Under normoxia (normal oxygen conditions) EGLN1 protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) and subsequent targeting for proteasome degradation.
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VGF or VGF nerve growth factor inducible is a secreted protein and neuropeptide precursor that may play a role in regulating energy homeostasis, metabolism and synaptic plasticity. The protein was first discovered in 1985 by Levi et al. in an experiment with PC12 cells and its name is non-acronymic. VGF gene encodes a precursor which is divided by proteolysis to polypeptides of different mass, which have a variety of functions, the best studied of which are the roles of TLQP-21 in the control of appetite and inflammation.
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Viability was very low in a strain lacking pol II, pol IV, and pol V, the three SOS-inducible DNA polymerases, indicating that translesion synthesis is conducted primarily by these specialized DNA polymerases. A bypass platform is provided to these polymerases by Proliferating cell nuclear antigen (PCNA). Under normal circumstances, PCNA bound to polymerases replicates the DNA. At a site of lesion, PCNA is ubiquitinated, or modified, by the RAD6/RAD18 proteins to provide a platform for the specialized polymerases to bypass the lesion and resume DNA replication.
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Systemin activates processes which help tomato deter insect herbivores, such as this tomato hornworm Systemin plays a critical role in defence signalling in tomato. It promotes the synthesis of over 20 defence-related proteins, mainly antinutritional proteins, signaling pathway proteins and proteases. The over-expression of the prosystemin resulted in a significant decrease of the larvae damage, indicating that a high level of constitutive protection is superior to an inducible defence mechanism. However, the continuous activation of prosystemin is costly, affecting the growth, the physiology and the reproductive success of tomato plants.
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In 1985, Lin et al isolated the human erythropoietin gene from a genomic phage library and used it to produce EPO. In 1989, the US Food and Drug Administration approved the hormone Epogen for use in certain anemias. Gregg L. Semenza and Peter J. Ratcliffe studied the EPO gene and its oxygen-dependent regulation. Along with William Kaelin Jr., they were awarded the 2019 Nobel Prize in Physiology or Medicine for their discovery of hypoxia-inducible factor (HIF), which regulates the EPO gene, as well as other genes, in response to hypoxia.
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The form known as "black brush algae" (or "black beard algae", BBA for short) is a particular nuisance in aquaria, as few fish, even those widely promoted as algivores, will eat it. In natural ecosystems, this genus that infests aquariums is found in unpolluted lotic systems. It has been tested for germination and new growth using NO3 and PO4 fertilizers and such results came out negative for a decade's worth of observations. It has been shown to be inducible by limiting and varying the CO2 concentration in planted aquariums.
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The administration of 3-MC to pregnant mice results in the formation of lung tumors in the offspring. Miller et al. (1990) compared the effects of fetal versus adult exposure to 3-MC on both induction of aryl hydrocarbon hydroxylase (AHH) activity in lung and dependence of lung tumorigenesis on the Ah genotype. A single ip injection (in inducible fetal lung supernatants) of 100 mg/kg of 3-MC to the mothers resulted in a maximal 50-fold induction of AHH activity by 8 hr, which persisted for 48 hr.
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When exposed to tamoxifen, the dominant negative fragment changed the conformation of the fusion protein, became active, and could therefore interfere with CREB binding sites. One advantage of this inducible transgenic system is that the altered protein is constitutively present and can therefore be rapidly activated following the administration of tamoxifen. Use of the LBD system to knock down CREB protein function during training (using both contextual freezing and tone fear paradigms) produced a deficit in long-term, but not short-term, memory. Impairing CREB function did not impair retrieval of the consolidated memory.
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They then proceeded to train mice using auditory fear training to produce a fear memory. They proceeded to check which of the neurons were overexpressing CREB and then, using an inducible diphtheria-toxin strategy, they destroyed those neurons, resulting in persistent and strong memory erasure of the fear memory. Researchers have also found that the levels of the neurotransmitter, acetylcholine, can also effect which memories are most prominent in our minds. Due to the lack of understanding of the brain this technique of destroying neurons may have a much larger effect on the patient than just the removal of the intended memories.
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Some are "obligate CAM plants", i.e. they use only CAM in photosynthesis, although they vary in the amount of they are able to store as organic acids; they are sometimes divided into "strong CAM" and "weak CAM" plants on this basis. Other plants show "inducible CAM", in which they are able to switch between using either the or mechanism and CAM depending on environmental conditions. Another group of plants employ "CAM- cycling", in which their stomata do not open at night; the plants instead recycle produced by respiration as well as storing some during the day.
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In biological systems, temporal feedback is a ubiquitous signal transduction motif that allows systems to convert graded inputs into decisive, all-or-none digital outputs. A system with interlinked fast and slow feedback loops produces a dual-time switch, which is rapidly inducible and robust to noise during stimulus. In contrast, a single fast or slow loop is separately responsible for the speed of switching and the stability of switches. Computer simulation studies have shown that linking two loops of the same kind brings no overall advantage over having a single loop, however the dual-loop switch performs in a monostable regime.
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The D’Andrea laboratory at the Dana Farber Cancer Institute focuses on the molecular events involved in normal blood cell formation and on the molecular cause of leukemia and other cancers. His laboratory examines molecular signaling pathways and the resulting DNA damage response in mammalian cells. These pathways are often disrupted in cancer cells, accounting for chromosome instability and increased gene mutation frequency in human tumors. D'Andrea and his colleagues have identified and cloned a family of cytokine-inducible deubiquitinating enzymes that regulate hematopoietic cell growth by controlling the ubiquitin-mediated proteolysis of intracellular growth regulatory proteins.
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"Danger signals" and DAMPs are together with pathogen-associated molecular patterns (PAMPs) called alarmins and they are recognized by pattern recognition receptors (PRRs) of APC cells. PRRs include Toll-like receptors (TLR), nucleotide oligomerization domain (NOD)-like receptors, retinoic acid inducible gene-I (RIG-I)-like receptors and C-type lectin-like receptors. They are not only at the surface of these cells, but we can find them in cytoplasm and incorporated in the membrane of endolysosomes. Stimulation of PRRs leads to activation of APC cell to process antigen, upregulate expression of costimulatory molecules and present antigen to T helper cells.
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The myeloid cell nuclear differentiation antigen (MNDA) is detected only in nuclei of cells of the granulocyte-monocyte lineage. A 200-amino acid region of human MNDA is strikingly similar to a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Ifi-201, Ifi202, and Ifi-203, that are not regulated in a cell- or tissue-specific fashion. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response element in the 5' UTR, was significantly upregulated in human monocytes exposed to interferon alpha. MNDA is located within 2,200 kb of FCER1A, APCS, CRP, and SPTA1.
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Moshe Oren at the Weizmann Institute of Science, he demonstrated that SIAH1 targets NUMB (gene), a protein involved in directing cell fate choices, for ubiquitin- mediated degradation. SIAH1 is a p53-inducible gene, active in the process of cell death and tumor suppression by a mechanism consisting of ubiquitination and proteasomal degradation of specific target proteins. Approaching cancer research with a different angle, not asking why the normal cells become malignant, but rather from the patients expectations: how do my tumor cells quit their malignant status, and thus, revert?, Laurent Susini joined Molecular Engines Laboratories (M.
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During this time she co-wrote the 'Genetics and Biochemistry of Pseudomonas'. Her aim in this paper was to present in one volume the fundamentals, basic methodology, and specific applications of gas- liquid chromatography in microbiology and medicine. In addition to this, some of her most well-recognised papers are: Hydrogen Sulphide Production by Bacteria, An Inducible Amidase Produced by a Strain of Pseudomonas aeruginosa, Biochemical Classification of Proteus and Providence Cultures Butyramide-using Mutants of Pseudomonas aeruginosa 8602 which Produce an Amidase with Altered Substrate Specificity. Her major field of research was bacterial enzymes production and metabolism.
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Patients with GEFS+ type 3 have mutations in the GABRG2 gene, which encodes the GABAA γ2 subunit (figure 2). The first mutation discovered in GABRG2 was K289M, in the extracellular region linking membrane-spanning domains M2 and M3. Oocytes injected with α1, β2, and γ2 subunits produce large GABA inducible currents whereas those injected with K289M mutant instead of wild-type subunits produce currents much smaller (about 10% of wild-type). This abnormal current is not the result of non-incorporation of mutant subunits since mutant containing receptors are still sensitive to benzodiazepines, a property for which functional γ subunits are required.
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This behavior reduces exposure of diurnal visual predators (such as many fish) by finding refuge in the dark near the bottom and then feeding undisturbed during the night in the food-rich upper water layers. The basis of this behaviour is phototactic behavior (movements of entire organisms to, or away from, a light source). In D. magna phototactic behavior has an innate component (genetic) and an inducible component (for example in the presence of fish kairomones). In Diel horizontal migration, D. magna finds refuge within submerged plant-beds near the shore during daytime and migrates to open waters during the night.
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Hypodysfibrinogenemia is usually diagnosed in individuals who: have a history of abnormal bleeding or thrombosis or are a close blood relative of such an individual. Initial laboratory findings include a decrease in serum fibrinogen mass levels as measured by immunoassay plus a reduction in inducible blood clot formation so that the ratio of functionally-detected fibrinogen mass (i.e. detected in induced clots) to immunoassay-detected fibrinogen mass is abnormally low, i.e. <0.7. This contrast with individuals with congenital dysfibrinogenemia who exhibit normal levels of fibrinogen as measured by immunoassay but low functionally-detected to immunoassay-detected fibrinogen mass ratios, i.e. <0.7.
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They were originally classified as "constitutively expressed" and "Ca2+ sensitive" but it is now known that they are present in many different cell types and that expression is regulated under specific physiological conditions. In NOS1 and NOS3, physiological concentrations of Ca2+ in cells regulate the binding of calmodulin to the "latch domains", thereby initiating electron transfer from the flavins to the heme moieties. In contrast, calmodulin remains tightly bound to the inducible and Ca2+-insensitive isoform (iNOS or NOS2) even at a low intracellular Ca2+ activity, acting essentially as a subunit of this isoform. Nitric oxide may itself regulate NOS expression and activity.
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They are targeted against oncogenic receptors such as epidermal growth factor receptor (EGFR). Tumor eradication resulted when PD-L1 (also induced by IFN-β acting on DCs) was neutralized. DC function also may be adversely affected by the TME's hypoxic conditions, which induces PD-L1 expression on DCs and other myelomonocytic cells as a result of hypoxia-inducible factors-1α (HIF-1α) binding directly to a hypoxia-responsive element in the PD-L1 promoter. Even the aerobic glycolysis of cancer cells may antagonize local immune reactions via increasing lactate production, which induces the M2 TAM polarization.
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Acupuncture of Zusanli induces local serotonin release. Furthermore, the stimulation of this acupoint is shown to decrease inflammation, as evidenced by decreased cytokines (including interleukin 6) and inhibition of edema in a rat model of inflammation involving carrageenan injection. Zusanli activation also improves insulin sensitivity and cerebral blood flow (an effect mediated by nitric oxide), while it decreases sympathetic nerve activity and arterial pressure. An analgesic effect, mediated in part by nitric oxide as well, through the upregulation of inducible nitric oxide synthase (iNOS), an increase in endogenous opiates, muscarinic cholinergic receptors and serotonin receptors 5-HT1a and 5-HT3, was repeatedly evidenced.
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420x420px In response to drought conditions, there is an alteration of gene expression, induced by or activated by transcription factors (TFs). These TFs bind to specific cis- elements to induce the expression of targeted stress-inducible genes, allowing for products to be transcribed that help with stress response and tolerance. Some of these include dehydration-responsive element-binding protein (DREB), ABA-responsive element-binding factor (AREB), no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), and cup-shaped cotyledon (CUC). Much of the molecular work to understand the regulation of drought tolerance has been done in Arabidopsis, helping elucidate the basic processes below.
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A cloning vector need not contain suitable elements for the expression of a cloned target gene, such as a promoter and ribosomal binding site (RBS), many however do, and may then work as an expression vector. The target DNA may be inserted into a site that is under the control of a particular promoter necessary for the expression of the target gene in the chosen host. Where the promoter is present, the expression of the gene is preferably tightly controlled and inducible so that proteins are only produced when required. Some commonly used promoters are the T7 and lac promoters.
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Local initiation of HR in response to certain necrotrophic pathogens has been shown to allow the plants to develop systemic immunity against the pathogen. Scientists have been trying to exploit the ability of HR to induce systemic resistance in plants in order to create transgenic plants resistant to certain pathogens. Pathogen-inducible promoters have been linked to auto-active NLR genes to induce HR response only when the pathogen is present but not at any other time. This approach, however, has been mostly unfeasible as the modification also leads to a substantial reduction in plant yields.
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Chromosome 20 open reading frame 111, or C20orf111, is the hypothetical protein that in humans is encoded by the C20orf111 gene.: C20orf111 chromosome 20 open reading frame 111 C20orf111 is also known as Perit1 (peroxide inducible transcript 1), HSPC207, and dJ1183I21.1.Genecards It was originally located using genomic sequencing of chromosome 20. The National Center for Biotechnology Information, or NCBI, shows that it is located at q13.11 on chromosome 20, however the genome browser at the University of California- Santa Cruz (UCSC) websiteUCSC Genome Search shows that it is at location q13.12, and within a million base pairs of the adenosine deaminase locus.
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CYR61 was first identified as a protein encoded by a serum-inducible gene in mouse fibroblasts. Other highly conserved homologs were later identified to comprise the CCN protein family (CCN intercellular signaling protein). The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), WISP2 (CCN5), and WISP3 (CCN6) comprise the six members of the family in vertebrates and have been renamed CCN1-6 in order of their discovery by international consensus.
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Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene. This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3).
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Proteasome subunit beta type-8 as known as 20S proteasome subunit beta-5i is a protein that in humans is encoded by the PSMB8 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Chymotrypsin-like" activity and is capable of cleaving after large hydrophobic residues of peptide.
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Proteasome subunit beta type-9 as known as 20S proteasome subunit beta-1i is a protein that in humans is encoded by the PSMB9 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide.
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Shimizu, K., Nakamura, H. & Ashiuchi, M. Salt-Inducible Bionylon Polymer from Bacillus Megaterium. Appl. Environ. Microbiol. 73:2378–2379 (2007) At least one strain of B. megaterium can be considered a halophile, as growth on up to 15% NaCl has been observed.Khan, J. A. Biodegradation of Azo Dye by Moderately Halotolerant Bacillus megaterium and Study of Enzyme Azoreductase Involved in Degradation. Advanced Biotech 10:21–27 (2011) Gram-stained Bacillus megaterium Phylogenetically, based on 16S rRNA, B. megaterium is strongly linked with B. flexus, the latter distinguished from B. megaterium a century ago, but only recently confirmed as a different species.
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Klebsiella aerogenes, previously known as Enterobacter aerogenes, is a Gram- negative, oxidase negative, catalase positive, citrate positive, indole negative, rod-shaped bacterium. The bacterium is approximately 1-3 microns in length, and is capable of motility via peritrichous flagella. K. aerogenes is a nosocomial and pathogenic bacterium that causes opportunistic infections including most types of infections. The majority are sensitive to most antibiotics designed for this bacteria class, but this is complicated by their inducible resistance mechanisms, particularly lactamase, which means that they quickly become resistant to standard antibiotics during treatment, requiring a change in antibiotic to avoid worsening of the sepsis.
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Transgenic mice homozygous for a null mutation of the JUP gene die around embryonic day 12 from substantial defects in adherens junctions and a lack of functional desmosomes in the heart. Further studies showed that cardiac fibers obtained from JUP-null embryonic mice had decreased passive compliance albeit normal attachment of sarcomeres to adherens junctions. In additional studies, an inducible cardiac-specific plakoglobin knockout mice were generated. Transgenic mice displayed a similar phenotype as arrhythmogenic right ventricular cardiomyopathy patients, with loss of cardiomyocytes, fibrosis and cardiac dysfunction, as well as alterations in desmosome protein content and gap junction remodeling.
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The intramolecular G-quadruplex structures are formed mostly through the abundant guanine sequence in the promoter region of this specific pathway. The cyclin-dependent cell cycle checkpoint kinase inhibitor-1 CDKN1A (also known as p21) gene harbours promoter G-quadruplex. Interaction of this G-quadruplex with TRF2 (also known as TERF2) resulted in epigenetic regulation of p21, which was tested using the G-quadruplex-binding ligand 360A. Hypoxia inducible factor 1ɑ, HIF-1ɑ, remains involved in cancer signaling through its binding to Hypoxia Response Element, HRE, in the presence of hypoxia to begin the process of angiogenesis.
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The developmentally active and heat shock inducible hsromega or hsrω gene in Drosophila produces multiple long non-coding RNA transcripts. This gene is transcriptionally active in almost all cell types of Drosophila and is the most actively induced following heat shock. A unique feature of the hsromega gene, which led to discovery of the 93D puff in 1970, is its singular inducibility with benzamide and a variety of other amides. The multiple transcripts of this gene include a nuclear >10kb long nuclear transcript, hsromega-n, and a 1.9kb nuclear transcript which after splicing produces a 1.2kb cytoplasmic transcript.
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Proteasome subunit beta type-7 as known as 20S proteasome subunit beta-2 is a protein that in humans is encoded by the PSMB7 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide.
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The gene PSMB7 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit (beta 2, according to systematic nomenclature) is downregulated by gamma interferon due to an alternatively elevated expression of inducible subunit beta2i, which leads to augmented incorporation of beta2i instead of beta2 into the final assembled 20S complex. The human protein proteasome subunit beta type-7 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 5.61.
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Proteasome subunit beta type-5 as known as 20S proteasome subunit beta-5 is a protein that in humans is encoded by the PSMB5 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "chymotrypsin-like" activity and is capable of cleaving after large hydrophobic residues of peptide.
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In yaks, hypoxia-inducible factor 1 (HIF-1) has high expression in the brain, lung and kidney, showing that it plays an important role in the adaptation to low oxygen environment. On 1 July 2012 the complete genomic sequence and analyses of a female domestic yak was announced, providing important insights into understanding mammalian divergence and adaptation at high altitude. Distinct gene expansions related to sensory perception and energy metabolism were identified. In addition, researchers also found an enrichment of protein domains related to the extracellular environment and hypoxic stress that had undergone positive selection and rapid evolution.
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Protein phosphatase 1 regulatory subunit 15A also known as growth arrest and DNA damage-inducible protein GADD34 is a protein that in humans is encoded by the PPP1R15A gene. The Gadd34/MyD116 gene was originally discovered as a member in a set of gadd and MyD mammalian genes encoding acidic proteins that synergistically suppress cell growth. Later on it has been characterized as a gene playing a role in ER stress-induced cell death, being a target of ATF4 that plays a role in ER-mediated cell death via promoting protein dephosphorylation of eIF2α and reversing translational inhibition.
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Therefore, because the addition of pseudouridine happens during the normal processing of tRNA, it is not considered an epitranscriptomic mark. However, pseudouridine acts as an epigenetic mark in mRNAs and ncRNAs of the brain, since pseudouridylation in these two RNAs responds dynamically to stress and differentiation in the cell, giving reason to believe that pseudouridylation may act as an important regulatory mechanism for RNA function. Pseudouridylation in mRNA can be conserved, tissue-specific or inducible, which reflects plasticity and regulatory function. Furthermore, expression of TRBU1, which is mostly expressed in the brain, goes up due to fear conditioning.
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HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFα-inducible monocyte binding to HUVECs. Comparison of the HoxA5 promoter methylation profile across cell types from the least differentiated (human embryonic stem cells) to the most endothelial-like (human umbilical vein endothelial cells, or HUVECs) shows that the HoxA5 promoter is normally heavily methylated in non-differentiated cells and becomes demethylated as cells differentiate down the endothelial lineage. HoxA5 contains a C-Amp Response Elements (CRE) in its promoter. POL2 and CTCF binding are enriched at the CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.
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The protein encoded by the VHL gene is the substrate recognition component of a protein complex that includes elongin B, elongin C, and cullin-2, and possesses E3 ubiquitin ligase activity. This complex is involved in the ubiquitination and subsequent degradation of hypoxia-inducible factors (HIFs), which are transcription factors that play a central role regulating gene expression in response to changing oxygen levels. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed. The regulation of HIF1α by pVHL.
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HIF1α causes the transcription of genes that contain the hypoxia response element. In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. The resultant protein is produced in two forms, an 18 kDa and a 30 kDa protein that functions as a tumor suppressor. The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation. The most researched of these targets is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression of a number of angiogenesis related factors.
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Expression of these genes answered the age-old question of when the embryo decides to make a nervous system: Sive showed that future brain cells are set aside when the embryo is just a ball of cells. Function of these genes, including otx2 and zic1 (opl), was studied using hormone-inducible fusion proteins, a technique first used in embryos by Sive. She also developed the first zebrafish ‘explant’ culture method, and so identified cell interactions that initiate brain development. As well, Sive identified retinoic acid as a regulator of brain patterning, and demonstrated its activity on expression of hindbrain Hox genes.
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Significant research has revealed a large number of natural products derived from fungi that have potential for anti-inflammatory and anticancer properties for human cancer cells. Some compounds have even been tested in mouse models of human cancer to demonstrate their therapeutic benefits. Oxaspiradion is one of the fungi- derived natural products with an ability to aid in anti-inflammatory and anticancer measures. Isolated from C. subspirale, oxaspirodion inhibits inducible TNF-an expression and inhibits the activation of the transcription factor NF-kappaB. Inflammatory diseases, such as, septic shock, rheumatoid arthritis and Crohn’s disease, involve TNF-a as the main pro-inflammatory cytokine.
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Dominant arbuscular mycorrhizal fungi can prevent the invasion of non-mycorrhizal plants on land where they have established symbiosis and promote their mycorrhizal host. Recent research has shown that AM fungi release an unidentified diffusional factor, known as the myc factor, which activates the nodulation factor's inducible gene MtEnod11. This is the same gene involved in establishing symbiosis with the nitrogen fixing, rhizobial bacteria (Kosuta et al. 2003). When rhizobium bacteria are present in the soil, mycorrhizal colonization is increased due to an increase in the concentration of chemical signals involved in the establishment of symbiosis (Xie et al. 2003).
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PCC6803 promoters that have been used in synthetic constructs, although this leads to cross talk and non-orthogonal or non- specific gene expression. A handful of Anderson promoters (a group of constitutive promoters collected from a combinatorial library based on the consensus -35 (5'-TTGACA-3) and -10 (5’-TATAAT-3’) regions), represented best by BBa_J23101, have been demonstrated to function in Synechocystis sp. PCC6803. The iGem Registry hosts these promoter sequences as part of the BioBrick initiative to create interchangeable genetic parts. For synthetic biology, it is critical to have inducible promoters, or genes that can be turned on/off on demand.
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In the cytoplasm, dsRNA receptors, such as RIG-I (retinoic acid-inducible gene I) and MDA-5 (melanoma differentiation associated gene 5), detect dsRNAs and initiate signaling pathways that translocate IRF-3 (interferon regulatory factor 3) and other transcription factors to the nucleus. Translocated transcription factors activate expression of interferons 𝛂 and 𝛃, and these initiate adaptive immunity. NP encoded in Lassa mammarenavirus is essential in viral replication and transcription, but it also suppresses host innate IFN response by inhibiting translocation of IRF-3. NP of Lassa mammarenavirus is reported to have an exonuclease activity to only dsRNAs.
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Although telomerase activation does not occur during the cell cycle of normal somatic human cells, the association between telomere elongation (especially elongation by telomerase) and tumor development emphasizes the importance of understanding when such elongation can occur during the cell cycle. Work with S. cerevisiae has identified telomerase activity as restricted to late S phase. Researchers generated S. cerevisiae strains with galactose-inducible shortened telomeres. They then used α factor to block cells with induced short telomeres in late G1 phase and measured the change in telomere length when the cells were released under a variety of conditions.
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Human red blood cells At high altitudes, there is a decrease in oxygen hemoglobin saturation. This hypoxic condition causes hypoxia-inducible factor 1 (HIF1) to become stable and stimulates the production of erythropoietin (EPO), a hormone secreted by the kidneys, EPO stimulates red blood cell production from bone marrow in order to increase hemoglobin saturation and oxygen delivery. Some athletes demonstrate a strong red blood cell response to altitude while others see little or no gain in red cell mass with chronic exposure. It is uncertain how long this adaptation takes because various studies have found different conclusions based on the amount of time spent at high altitudes.
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Carboxylation enzymes in the cytosol can, therefore, be kept separate from decarboxylase enzymes and RuBisCO in the chloroplasts, and a diffusive barrier can be established between the chloroplasts (which contain RuBisCO) and the cytosol. This enables a bundle-sheath-type area and a mesophyll-type area to be established within a single cell. Although this does allow a limited cycle to operate, it is relatively inefficient, with the occurrence of much leakage of from around RuBisCO. There is also evidence for the exhibiting of inducible photosynthesis by non-kranz aquatic macrophyte Hydrilla verticillata under warm conditions, although the mechanism by which leakage from around RuBisCO is minimised is currently uncertain.
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The BadA protein is another example of a TAA found in Bartonella henselae bacteria. Bartonella henselae is the causative agent of cat scratch disease, a normally harmless disease, but, in people with a weakened immune system, such as those undergoing chemotherapy or fighting AIDS, it is more serious as it can lead to bacillary angiomatosis. This a condition where benign tumours of the blood vessels undergo uncontrolled proliferation, causing knots to form in the smaller blood vessels, such as capillaries, restricting the flow of blood. This may be due to BadA's inducing the transcription of proangiogenic factors, as it activates of NF-κB as well as hypoxia-inducible factor 1.
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The molecular mechanisms that underlie persister cell formation, and antimicrobial tolerance are largely unknown. Persister cells are thought to arise spontaneously in a growing microbial population by a stochastic genetic switch, although inducible mechanisms of persister cell formation have been described. For instance, toxin-antitoxin systems, and a number of different stress responses such as the SOS response, the envelope stress response, and the starvation response have also been associated with persister cell formation in biofilms. Owing to their transient nature and relatively low abundance, it is hard to isolate persister cells in sufficient numbers for experimental characterization, and only a few relevant genes have been identified to date.
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HIF regulates interactions of cancer cells with ECM and ECM biosynthesis Traditionally, hypoxia leads to increased production of hypoxia-inducible factor (HIF-1), containing HIF-1α and HIF-1β subunits, that acts as a key regulatory transcription factor responsible for adaptive cellular changes. In humans, HIF-1 has been shown to up-regulate expression of genes affecting a range of target areas of physiology. These genes range from those involved in triggering an inflammatory response to those responsible for iron metabolism. Particularly notable when focusing on metabolism, HIF-1 is shown to affect glycolytic genes to cope with reductions in oxygen availability and consumption.
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Erythropoiesis-stimulating agents such as erythropoietin (EPO), darbepoetin (dEPO), hypoxia-inducible factor (HIF) stabilizers, methoxy polyethylene glycol-epoetin beta (CERA) and peginesatide (Hematide); growth hormone (hGH), insulin-like growth factors (IGF-1, etc.), fibroblast growth factors (FGFs), hepatocyte growth factors (HGF), mechano growth factors (MGFs), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), chorionic gonadotropin (banned in men only), somatotrophin (growth hormone), insulins and corticotrophins, corticosteroid mimics, and their releasing factor, are banned. Also banned are any other growth factor affecting muscle, tendon or ligament protein synthesis/degradation, vascularization, energy utilization, regenerative capacity or fiber type switching; and other substances with similar chemical structure or similar biological effects.
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The mechanisms and time of occurrence of hCONDELs are not entirely understood but given that conserved non-coding sequences play a major developmental role through regulation of genes, their loss in regions of deletions, it is expected that their loss in hCONDELs will result in developmental consequences that can be observed in human-specific traits. In situ hybridization experiments done by Mclean et al. by fusion of mouse constructs fused to basal promoter with LacZ expression for hCONDELs near the androgen receptor (AR) locus and the growth arrest and DNA-damage- inducible protein GADD45 gamma (GADD45G) locus suggest a role in deletions that affect regulatory sequences in humans.
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PKN3 is a protein kinase C-related molecule and thought to be an effector mediating malignant cell growth downstream of activated phosphoinositide 3-kinase (PI3K). It is thought that chronic activation of the phosphoinositide 3-kinase (PI3K)/PTEN signal transduction pathway contributes to metastatic cell growth and that PKN3 may mediate that growth.1 PKN3 is required for invasive prostate cell growth as assessed by 3D cell culture assays and in an orthotopic mouse tumor model by inducible expression of short hairpin RNA (shRNA). PKN3 may represent a target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of PI3K.
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Aryl hydrocarbon receptor nuclear translocator 2 is a protein that in humans is encoded by the ARNT2 gene. This gene encodes a member of the basic-helix- loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. The encoded protein acts as a partner for several sensor proteins of the bHLH-PAS family, forming heterodimers with the sensor proteins that bind regulatory DNA sequences in genes responsive to developmental and environmental stimuli. Under hypoxic conditions, the encoded protein complexes with hypoxia-inducible factor 1alpha in the nucleus and this complex binds to hypoxia-responsive elements in enhancers and promoters of oxygen-responsive genes.
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CARP has a relatively short half-life being longer in cardiomyocytes than endothelial cells; and CARP is degraded by the 26S proteasome via a PEST degron. In animal models of disease and injury, CARP has been characterized to be a stress-inducible myofibrillar protein. CARP has been shown to play a role in skeletal muscle structure remodeling, and repair, being expressed in skeletal muscle near myotendinous junctions, and in vascular smooth muscle cells, as a downstream target of TGF-beta/Smad sigmaling in response to balloon injury and atherosclerotic plaques. Further studies have identified a role for CARP in initiation and regulation of arteriogenesis.
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Adenosine is used as a vasodilator, via the A2A receptor, to increase the difference in perfusion between myocardial territories supplied by normal and stenosed coronary arteries. A continuous intravenous infusion is administered for a few minutes until there are hemodynamic signs of vasodilatation, then a bolus of contrast medium is administered while acquiring saturation recovery images of the heart with a high temporal resolution readout. A positive result is evident from an inducible myocardial perfusion defect. Cost and availability mean that its use is often confined to patients with intermediate pre-test probability, but it has been shown to reduce unnecessary angiography compared with guidelines-directed care.
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Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene. Ubiquitin-specific protease 20 (USP20), also known as ubiquitin-binding protein 20 and VHL protein-interacting deubiquitinating enzyme 2 (VDU2), is a cysteine protease deubiquitinating enzyme (DUB). The catalytic site of USP20, like other DUBs, contains conserved cysteine and histidine residues that catalyse the proteolysis of an isopeptide bond between a lysine residue of a target protein and a glycine residue of a ubiquitin molecule. USP20 is known to deubiquitinate a number of proteins including thyronine deiodinase type 2 (D2), Hypoxia-inducible factor 1α (HIF1α), and β2 adrenergic receptor (β2AR).
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When this mutant subunit is expressed in cells with wild-type α and β subunits it produces non-functional receptors. Since wild-type α and β subunits expressed alone are able to produce GABA inducible current this indicates that the mutation either prevents both coassembly of the mutant and wild-type subunits but also coassembly of the wild-type α and β subunits or prevents proper trafficking of the formed receptor to the membrane. Fusion of GFP onto this mutated subunit has indicated that it is localized to the endoplasmic reticulum instead of the cell membrane. As with other known GEFS+ type 3 mutation, Q351X likely results in neuronal hyperexcitability.
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While B. pseudomallei can survive in phagocytic cells, these cells can kill B. pseudomallei by several mechanisms. Macrophages activated by interferon gamma have improved the killing of B. pseudomallei via the production of inducible nitric oxide synthase. Acidification of the endosome and degradation of the bacteria is also possible, however, the bacterial capsule and LPS makes B. pseudomallei resistant to lysosomal degradation. Once B. pseudomallei escapes into the host cytosol, it can be recognized by pattern recognition receptors such as NOD-like receptors, triggering the formation of the inflammasome and activation of caspase 1, which induces death of the host cell by pyroptosis and further activation of the immune system.
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The focus is on the metabolism of fermented glucose (Warburg effect) or oxidative glucose in tumours, the import of amino acids under the influence of HIF or oxidative stress. Numerous anti-cancer targets inactivated by Zinc Finger Nucleases and/or CRISPR-Cas9 (carbonic anhydrases CA9, CA12, CA2, bicarbonate carriers NBC, lactate/H+ Symporters MCT1, MCT4, their chaperone CD147/basigine, key amino acid carriers : LAT1, ASCT2, xCT and their chaperones CD98, CD44...) were analyzed on tumor lines (colon, melanoma, breast, pancreas, lung)Chiche J., et al., « Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. », Cancer Res.
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This leads to a secondary SCI, whose symptoms include edema, cavitation of spinal parenchyma, reactive gliosis, and potentially permanent loss of function. During the SCI induced inflammatory response, several pro- inflammatory cytokines including interleukin 1β (IL-1β), inducible Nitric Oxide Synthase (iNOS), Interferon-γ (IFN-γ), IL-6, IL-23, and tumor necrosis factor α (TNFα) are secreted, activating local microglia and attracting various immune cells such as naive bone-marrow derived macrophages. These activated microglia and macrophages play a role in the pathogenesis of SCI. Upon infiltration of the injury site's epicenter, macrophages will undergo phenotype switching from an M2 phenotype to an M1-like phenotype.
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Duodenal cytochrome B (Dcytb) also known as cytochrome b reductase 1 is an enzyme that in humans is encoded by the CYBRD1 gene. Dcytb CYBRD1 was first identified as a ferric reductase enzyme which catalyzes the reduction of Fe3+ to Fe2+ required for dietary iron absorption in the duodenum of mammals. Dcytb mRNA and protein levels in the gut are increased by iron deficiency and hypoxia which acts to promote dietary iron absorption. The effect of iron deficiency and hypoxia on Dcytb levels are medicated via the HIF2 (Hypoxia inducible factor 2) transcription factor which binds to hypoxia response elements within the Dcytb promoter and increases transcription of the gene.
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Hence, this review has summarized the available information on the neurohealth properties of H. erinaceus mycelia enriched with erinacines, which may contribute to further research on the therapeutic roles of these mycelia. The safety of this mushroom has also been discussed. Although it has been difficult to extrapolate the in vivo studies to clinical situations, preclinical studies have shown that there can be improvements in ischemic stroke, Parkinson's disease, Alzheimer's disease, and depression if H. erinaceus mycelia enriched with erinacines are included in daily meals. Decreased levels of proinflammatory cytokines and inducible NO synthase (iNOS), however, have been detected in ischemic neurons after mycelia exposure.
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Effects of rapamycin and rapalogs on endothelial and tumor cells Tumor angiogenesis rely on interactions between endothelial vascular growth factors which can all activate the PI3K/AKT/mTOR in endothelial cells, pericytes, or cancer cells. Example of these growth factors are angiopoietin 1 (ANG1), ANG 2, basic fibroblast growth factor (bFGF), ephrin-B2, vascular endothelial growth factor (VEGF), and members of the tumor growth factor-β (TGFβ) superfamily. One of the major stimuli of angiogenesis is hypoxia, resulting in activation of hypoxia-inducible transcription factors (HIFs) and expression of ANG2, bFGF, PDGF, VEGF, and VEGFR. Inhibition of HIF1α translation by preventing PDGF/PDGFR and VEGF/VEGFR can result from mTOR inhibition.
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In the case of Leishmania, progeny are not generated in PMNs, but in this way they can survive and persist untangled in the primary site of infection. The promastigote forms also release Leishmania chemotactic factor (LCF) to actively recruit neutrophils, but not other leukocytes, for instance monocytes or NK cells. In addition to that, the production of interferon gamma (IFNγ)-inducible protein 10 (IP10) by PMNs is blocked in attendance of Leishmania, what involves the shut down of inflammatory and protective immune response by NK and Th1 cell recruitment. The pathogens stay viable during phagocytosis since their primary hosts, the PMNs, expose apoptotic cell-associated molecular pattern (ACAMP) signaling "no pathogen".
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Generation of reactive oxygen and reactive nitrogen species in the phagolysosome, implicated in respiratory burst. There are 3 main pathways for the generation of reactive oxygen species or reactive nitrogen species (RNS) in effector cells: #Superoxide dismutase (or alternatively, myeloperoxidase) generates hydrogen peroxide from superoxide. Hydroxyl radicals are then generated via the Haber- Weiss reaction or the Fenton reaction, of which are both catalyzed by Fe2+. O2•–\+ H2O2 —> •OH + OH– \+ O2 # In the presence of halide ions, prominently chloride ions, myeloperoxidase uses hydrogen peroxide to produce hypochlorous acid. H2O2 \+ Cl- —> ClO- \+ H2O # Nitric oxide synthase (the inducible isoform, iNOS, in immunity) catalyses the production of nitric oxide from L-arginine.
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Neuron-specific CELF family RNA-binding protein UNC-75 specifically binds to the UUGUUGUGUUGU mRNA stretch via its three RNA recognition motifs for the exon 7a selection in C. elegans' neuronal cells. As exon 7a is skipped due to its weak splice sites in non-neuronal cells, UNC-75 was found to specifically activate splicing between exon 7a and exon 8 only in the neuronal cells. The cold inducible RNA binding protein CIRBP plays a role in controlling the cellular response upon confronting a variety of cellular stresses, including short wavelength ultraviolet light, hypoxia, and hypothermia. This research yielded potential implications for the association of disease states with inflammation.
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Knockout mice of GPX4 die at embryonic day 8 and conditional inducible deletion in adult mice (neurons) results in degeneration and death in less than a month. Targeted disruption of the mitochondrial GPx4 isoform (mGPx4) caused infertility in male mice and disruption of the nuclear GPx4 isoform (nGPx4) reduced the structural stability of sperm chromatin, yet both knockout mouse models (for mGPx4 and nGPx4) were fully viable. Surprisingly, knockout of GPX4 heterozygously in mice (GPX4+/−) increases their median life span. Knockout studies with GPx1, GPx2, or GPx3 deficient mice showed that cytosolic GPx4 is so far the only glutathione peroxidase that is indispensable for embryonic development and cell survival.
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Proteasome subunit beta type-3, also known as 20S proteasome subunit beta-3, is a protein that in humans is encoded by the PSMB3 gene. This protein is one of the 17 essential subunitsAlongside alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i that contribute to the complete assembly of the 20S proteasome complex. In particular, proteasome subunit beta type-2, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognizes degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes.
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Transgenic mice over-expressing the EGF- like ligand betacellulin (BTC) exhibit increased cortical bone deposition; however, because the transgene is ubiquitously expressed in these mice, the identity of cells affected by BTC and responsible for increased cortical bone thickness remains unknown. We have therefore examined the influence of BTC upon mesenchymal stem cell (MSC) and pre-osteoblast differentiation and proliferation. BTC decreases the expression of osteogenic markers in both MSCs and pre-osteoblasts increases in proliferation require hypoxia-inducible factor-alpha (HIF-alpha), as an HIF antagonist prevents BTC-driven proliferation. Both MSCs and pre-osteoblasts express EGF receptors ErbB1, ErbB2, and ErbB3, with no change in expression under osteogenic differentiation.
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Proteasome subunit beta type-6 also known as 20S proteasome subunit beta-1 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB6 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-6, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Caspase- like" activity and is capable of cleaving after acidic residues of peptide.
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It has been shown that in cancer cell lines, UV-inactivated SeV triggers the production of an intercellular adhesion molecule -1 (ICAM-1, CD54), which is a glycoprotein that serves as a ligand for macrophage-1 antigen (Mac-1) and lymphocyte function-associated antigen 1 (LFA-1 (integrin)). Mac-1 and LFA-1 are receptors found on leukocytes. This induced production happens through the activation of nuclear factor-κB downstream of the mitochondrial antiviral signaling pathway and the retinoic acid-inducible gene I. The increased concentration of ICAM-1 on the surface of cancer cells, which is triggered by SeV, increases the vulnerability of these cells to natural killer cells.
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The research and application of inducing plant system resistance have been encouraging but are not yet a major factor in controlling plant pathogens. Incorporation into integrated pest management programs have shown some promising results. There is research regarding defense against leaf chewing insect pests, by the activation of jasmonic acid signalling triggered by root- associated microorganisms. Some ongoing research into ISR includes (1) how to systematically improve the selection of induction factors; (2) the injury of induced factors; (3) the phenomenon of multi-effect of induced factors; (4) the effects of chemical induction factors on environmental factors; (5) Establishment of population stability of multivariate biological inducible factor.
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By placing the hybrid proteins under the control of IPTG-inducible lac promoters, they are expressed only on media supplemented with IPTG. Further, by including different antibiotic resistance genes in each genetic construct, the growth of non-transformed cells is easily prevented through culture on media containing the corresponding antibiotics. This is particularly important for counter selection methods in which a lack of interaction is needed for cell survival. The reporter gene may be inserted into the E. coli genome by first inserting it into an episome, a type of plasmid with the ability to incorporate itself into the bacterial cell genome with a copy number of approximately one per cell.
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In stress echocardiography (see Cardiac stress test), the regional dysfunction due to ischemia will become evident when the myocardial oxygen demand surpasses the Coronary flow reserve of a stenosed coronary artery. Strain rate imaging during stress has been shown to give incremental value over ordinary echocardiography, both diagnosticVoigt JU, Exner B, Schmiedehausen K, Huchzermeyer C, Reulbach U, Nixdorff U, Platsch G, Kuwert T, Daniel WG, Flachskampf FA. Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia. Circulation. 2003;107:2120-6Ingul CB, Stoylen A, Slordahl SA, Wiseth R, Burgess M, Marwick TH. Automated analysis of myocardial deformation at dobutamine stress echocardiography: an angiographic validation. J Am Coll Cardiol.
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The W box is a deoxyribonucleic acid (DNA) cis-regulatory element sequence, (T)TGAC(C/T), which is recognized by the family of WRKY transcription factors. Functionality and conservation of the W-box element across plant species has been shown by gel shift experiments, random binding site selection, yeast one- hybrid screens and co-transfection assays performed with many different WRKY proteins. In silico-based studies together with functional studies of plant promoters have identified clusters of W-boxes in stress-inducible promoters. The binding of WRKY proteins to W-boxes is a feature of both biotic and abiotic stress responses, together with other plant processes such as germination.
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Example of a T-REx system controlling the expression of shRNA Tetracycline- Controlled Transcriptional Activation is a method of inducible gene expression where transcription is reversibly turned on or off in the presence of the antibiotic tetracycline or one of its derivatives (e.g. doxycycline). Tetracycline-controlled gene expression is based upon the mechanism of resistance to tetracycline antibiotic treatment found in Gram-negative bacteria. In nature, the Ptet promoter expresses TetR, the repressor, and TetA, the protein that pumps tetracycline antibiotic out of the cell. The difference between Tet-On and Tet-Off is not whether the transactivator turns a gene on or off, as the name might suggest; rather, both proteins activate expression.
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Nucleoporins (Nups) are the main constituent proteins of NPCs and have been shown to play multiple roles in mediating several processes involved in gene gating. While it has been known that the nuclear periphery serves as the primary location for most heterochromatin, telomeric and centrosomal DNA, studies in the yeast Saccharomyces cerevisiae have shown that NPCs containing Nup2p and Prp20p create boundaries of active gene expression near the nuclear envelope and prevent the spread of heterochromatin at the nuclear periphery. These Nup2p and Prp20p proteins also provide a location for the binding of chromatin. Some inducible genes in yeast been shown to re-locate to the nuclear periphery by binding NPCs composed of specific Nups.
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Stasis excacerbates hypoxia, and this state is linked to the activation of white blood cells (leukocytes) and the endothelium. Specifically, the two pathways of hypoxia-inducible factor-1 (HIF-1) and early growth response 1 (EGR-1) are activated by hypoxia, and they contribute to monocyte and endothelial activation. Hypoxia also causes reactive oxygen species (ROS) production that can activate HIF-1, EGR-1, and nuclear factor-κB (NF-κB), which regulates HIF-1 transcription. HIF-1 and EGR-1 pathways lead to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filled microvesicles, which presumably initiate fibrin deposition (via thrombin) after binding the endothelial surface.
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The gene coding for human SAA1 is one of the 4 SAA genes mapped to a region in the short arm on Chromosome 15. Two of these genes, SAA1 and SAA2, are inducible during acute- phase response, whereas SAA3 is a pseudogene in humans and SAA4 is constitutively expressed in a variety of tissues and cells. Single nucleotide polymorphisms (SNPs) are found in SAA1 in both coding and non-coding sequences, with those located in the coding sequence defining 5 isoforms of SAA1 (SAA1.1 – 1.5). Genetic studies have shown association of some of these SNPs with the disposition to several human diseases including familiar Mediterranean fever, coronary artery diseases, cerebral infarction, and osteoporosis.
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With techniques for cloning genes, Boman's group was able to continue studies on immune genes in Cecropia. At the same time, the field of innate immunity rapidly expanded, benefitting from the genetic tools available in Drosophila in the search to understand how insect immunity recognizes and signals following infection. From these initial studies, a number of insect antimicrobial peptides and other immune proteins were characterized, and these peptides have been used extensively as readouts of immune challenge. Owing to Boman's discovery, immune-inducible peptides were used to identify competent or deficient immune responses, ultimately leading to the Nobel Prize for Physiology or Medicine being awarded to Jules Hoffmann for his work on insect immune signalling.
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The type of regulation that the lac operon undergoes is referred to as negative inducible, meaning that the gene is turned off by the regulatory factor (lac repressor) unless some molecule (lactose) is added. Because of the presence of the lac repressor protein, genetic engineers who replace the lacZ gene with another gene will have to grow the experimental bacteria on agar with lactose available on it. If they do not, the gene they are trying to express will not be expressed as the repressor protein is still blocking RNAP from binding to the promoter and transcribing the gene. Once the repressor is removed, RNAP then proceeds to transcribe all three genes (lacZYA) into mRNA.
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Moreover, to increase their pathogen-killing ability, they produce increased amounts of chemicals called reactive oxygen species (ROS) and nitrogen radicals (caused by upregulation of inducible NO synthase iNOS). Thanks to their ability to fight pathogens, M1 macrophages are present during acute infectious diseases. A number of studies have shown that bacterial infection induces polarization of macrophages toward the M1 phenotype, resulting in phagocytosis and intracellular killing of bacteria in vitro and in vivo. For instance, Listeria monocytogenes, a Gram positive bacteria causing listeriosis is shown to induce an M1 polarization, as well as Salmonella typhi (the agent of typhoid fever) and Salmonella typhimurium (causing gastroenteritis), which are shown to induce the M1 polarization of human and murine macrophages.
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The AP-2 alpha protein acts as a sequence- specific DNA-binding transcription factor recognizing and binding to the specific DNA sequence and recruiting transcription machinery. Its binding site is a GC-rich sequence that is present in the cis-regulatory regions of several viral and cellular genes. AP2-alpha is a 52-kD retinoic acid-inducible and developmentally regulated activator of transcription that binds to a consensus DNA-binding sequence GCCNNNGGC in the SV40 and metallothionein promoters. AP-2 alpha is expressed in neural crest cell lineages with the highest levels of expression corresponding to early neural crest cells, suggesting that AP-2 alpha plays a role in their differentiation and development.
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The first is that there are various inactivating nucleotide variations in the human counterpart of the enhancer element that regulates LPS/IFNγ induced expression of the mouse NOS2 gene. The second is because of the absence of a nuclear factor in human macrophages that is required for optimum expression of gene NOS2 (LPS-inducible nuclear factor-kappa B/Rel complex). It is assumed that the difficulty in verifying NOS2 is due to a much more tightly controlled expression in human AMs as compared to that in the rodent AMs. NOS2 is part of an autoregulatory feedback loop, wherein an allergen or provoker stimulates inflammatory cytokine production, which in turn stimulates NO production, and NO down-regulates cytokine production.
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Like all other tailed bacteriophages cyanophages have a tail and a protein capsid surrounding genetic material. The double-stranded DNA is approximately 45 kbp long and in some cyanophages encodes photosynthetic genes, an integrase, or genes involved with phosphate metabolism (phosphate-inducible). The tail binds the virus to the host cell and transfers viral DNA to the host cell upon infection. Based on morphological characteristics, cyanophages are placed into the families Myoviridae, Podoviridaeand Siphoviridae, and although not formally recognized by the International Committee on Taxonomy of Viruses, historically cyanophages have been further classified into as a Cyanomyovirus, Cyanopodovirus or Cyanostylovirus based on which of the three families in which they are grouped.
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Cancer therapy by inhibition of negative immune regulation (CTLA4, PD1) Honjo has established the basic conceptual framework of class switch recombination. He presented a model explaining antibody gene rearrangement in class switch and, between 1980 and 1982, verified its validity by elucidating its DNA structure. He succeeded in cDNA clonings of IL-4 and IL-5 cytokines involved in class switching and IL-2 receptor alpha chain in 1986, and went on further to discover AID in 2000, demonstrating its importance in class switch recombination and somatic hypermutation. In 1992, Honjo first identified PD-1 as an inducible gene on activated T-lymphocytes, and this discovery significantly contributed to the establishment of cancer immunotherapy principle by PD-1 blockade.
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Shear stress leads to the activation and expression of all nitric oxide synthetase (NOS) isoforms and nitric oxide production, followed by vascular endothelial growth factor (VEGF) secretion, which induces monocyte chemoattractant protein-1 (MCP-1) synthesis in the endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from inducible nitric oxide synthetase (iNOS), which is essential for arteriogenesis.
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Proteasome subunit beta type-1 also known as 20S proteasome subunit beta-6 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB1 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-1, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes.
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Proteasome subunit beta type-4 also known as 20S proteasome subunit beta-7 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB4 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-2, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes.
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Finally, ISG15 could also be detected as an un-conjugated intracellular molecule with functions independent of ISGylation. The discovery of humans deficient in ISG15 elucidated the importance of these functions in human biology. ISG15-deficient patients were first identified by their susceptibly to BCG-strain mycobacteria, owing to the essential function of free ISG15 to potentiate the IFN-gamma / Interleukin-12 axis Surprisingly, despite the IFN- inducible nature of ISG15 and the previously-ascribed antiviral functions in mice, ISG15-deficient patients showed no susceptibility to viral infections. In fact, follow-up studies uncovered enhanced type I IFN signatures, manifesting as basal ganglia calcifications akin to TORCH infection but without an infectious etiology.
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Proteasome subunit beta type-2 also known as 20S proteasome subunit beta-4 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB2 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-2, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes.
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Coinfections or immunizations may enhance viral replication by inducing a response and activation of the immune system. This activation facilitates the three key stages of the viral life cycle: entry to the cell; reverse transcription and proviral transcription. Chemokine receptors are vital for the entry of HIV into cells. The expression of these receptors is inducible by immune activation caused through infection or immunization, thus augmenting the number of cells that are able to be infected by HIV-1. Both reverse transcription of the HIV-1 genome and the rate of transcription of proviral DNA rely upon the activation state of the cell and are less likely to be successful in quiescent cells.
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Traditionally, inflammasomes have mainly been studied in professional immune cells of the innate immune system, such as macrophages. More recent studies, however, indicate high levels of inflammasome component expression in epithelial barrier tissues, where they have been shown represent an important first line of defense. Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or danger- associated molecular patterns (DAMPs) generated by the host cell. Pattern recognition receptors involved in inflammasomes comprise NLRs (nucleotide- binding oligomerization domain and leucine-rich repeat-containing receptors) as well as AIM2 (absent in melanoma 2), IFI16 (IFN-inducible protein 16 ) as well as pyrin.
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A study in mice has shown that IL-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction. IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and Th1 T cells. It also displays a potent ability to suppress the antigen-presentation capacity of antigen presenting cells; however, it is also stimulatory towards certain T cells (Th2) and mast cells and stimulates B cell maturation and antibody production. IL-10 checks the inducible form of Cyclo-oxygenase, Cyclo-oxygenase-2 (COX-2).
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Adding a synthetic control mechanism to engineered T cells allows doctors to precisely control the persistence or activity of the T cells in the patient's body, with the goal of reducing toxic side effects. The major control techniques trigger T cell death or limit T cell activation, and often regulate the T cells via a separate drug that can be introduced or withheld as needed. Suicide genes: Genetically modified T cells are engineered to include one or more genes that can induce apoptosis when activated by an extracellular molecule. Herpes simplex virus thymidine kinase (HSV-TK) and inducible caspase 9 (iCasp9) are two types of suicide genes that have been integrated into CAR-T cells.
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Double stranded RNA viruses are recognized by either the transmembrane toll-like receptor 3 (TLR3) or by one of two cytosolic proteins, retinoic acid-inducible gene I (RIG-I)-like receptors and melanoma differentiation-associated gene 5 (MDA5). RIG-I and MDA5 differ in the viral RNA that they recognize, but they share many structural features, including the N-terminal CARD that allows them to bind to MAVS. MAVS activation leads to the increased levels of pro- inflammatory cytokines via activation of transcription factors, nuclear factor kB (NF-kB), interferon regulatory factor 1 (IRF1), and interferon regulatory factor 3 (IRF3). NFkB, IRF1, and IRF3 are transcription factors and play critical roles in the production of cytokines.
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The inducible pathway (iNOS) of nitrogen oxide synthesis in phagocytes can generate large amounts of NO that trigger apoptosis and kill other cells. In vitro studies indicate that phagocyte-dependent generation of NO at concentrations greater than 400-500 nM triggers apoptosis in nearby cells and that this effect may act in a manner similar to Specialized pro- resolving mediators to dampen and reverse inflammatory responses by neutralizing and then speeding the clearance of pro-inflammatory cells from inflamed tissues. However, the role of ·NO in inflammation is complex with model studies involving viral infection suggesting that this gaseous mediator can also promote inflammation. In response, many bacterial pathogens have evolved mechanisms for nitric oxide resistance.
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Identification of constitutive and inducible forms of nitric oxide synthase in human platelets. Journal of Laboratory and Clinical Medicine 125:370-377, 1995. #Yang BC, Phillips MI, ..... Mehta JL. Critical role of AT1 receptor expression after ischemia-reperfusion in isolated rat hearts: Beneficial effect of antisense oligodeoxynucleotides directed at AT1 receptor mRNA. Circulation Research 1998; 83:552-559. #Li DY, Mehta JL. Antisense to LOX-1 inhibits ox-LDL- mediated upregulation of MCP-1 expression and monocyte adhesion to human coronary artery endothelial cells. Circulation 2000;101;2889-2895. #Chen J, Liu Y, Liu H, Hermonat PL, Mehta JL. Molecular dissection of angiotensin II- activated human LOX-1 promoter. Arteriosclerosis, Thrombosis and Vascular Biology 2006;26:1163-1168.
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Transcription of the cloned gene is a necessary component of the vector when expression of the gene is required: one gene may be amplified through transcription to generate multiple copies of mRNAs, the template on which protein may be produced through translation. A larger number of mRNAs would express a greater amount of protein, and how many copies of mRNA are generated depends on the promoter used in the vector. The expression may be constitutive, meaning that the protein is produced constantly in the background, or it may be inducible whereby the protein is expressed only under certain condition, for example when a chemical inducer is added. These two different types of expression depend on the types of promoter and operator used.
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Several of these inducible genes, including GAL1, INO1, TSA2, and HSP104 contain gene recruitment sequences (GRSs) found in the promoter, which are necessary for the attachment of the gene to the NPC by way of DNA binding to specific Nups. This initial relocation of genes containing GRSs requires the action of Snf1-p dependent Spt-Ada-Gcn5 acetyltransferase (SAGA), a chromatin remodeling complex, as well as several mRNA export proteins, for their transcriptional activation at the nuclear periphery. In the fruit fly Drosophila melanogaster large stretches of chromatin are bound to Nups Nup153 and Megator. These genomic regions are often found on the male X chromosome, which exhibits high levels of transcriptional activity due to dosage compensation; these regions of chromatin are termed Nup-associated regions (NARs).
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A gain-of- function mutation in SGK1, or serum and glucocorticoid-inducible kinase 1, can lead to a shortening of the QT interval, which represents the repolarization time of the cardiac cells after a cardiac muscle contraction action potential. SGK1 does this by interacting with the KvLQT1 channel in cardiac cells, stimulating this channel when it is complex with KCNE1. SGK1 stimulates the slow delayed rectifier potassium current through this channel by phosphorylating PIKfyve, which then makes PI(3,5)P2, which goes on to increase the RAB11-dependent insertion of the KvLQT1/KCNE1 channels into the plasma membrane of cardiac neurons. SGK1 phosphorylates PIKfyve, which results in regulated channel activity through RAB11-dependent exocytosis of these KvLQT1/KCNE1-containing vesicles.
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MSOT based on in situ expression of fluorescent proteins can take advantage of tissue- and development-specific promoters, allowing imaging of specific parts of an organism at specific stages of development. For example, eGFP and mCherry fluorescent proteins have been imaged in model organisms such as Drosophila melanogaster pupae and adult zebrafish, and mCherry has been imaged in tumor cells in the mouse brain. This transgenic approach is not limited to fluorescent proteins: infecting tissue with a vaccinia virus carrying the tyrosinase gene allows in situ production of melanin, which generates strong optoacoustic signal for MSOT.R.J. Paproski, A. Heinmiller, K. Wachowicz, R.J. Zemp, "Multi-wavelength photoacoustic imaging of inducible tyrosinase reporter gene expression in xenograft tumors", Sci Rep 4 (2014) 5329.
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The fossil record shows that osteocytes were present in bones of jawless fish 400 to 250 million years ago. Osteocyte size has been shown to covary with genome size; and this relationship has been used in paleogenomic research. During bone formation, an osteoblast is left behind and buried in the bone matrix as an "osteoid osteocyte", which maintains contact with other osteoblasts through extended cellular processes. The process of osteocytogenesis is largely unknown, but the following molecules have been shown to play a crucial role in the production of healthy osteocytes, either in correct numbers or specific distributions: matrix metalloproteinases (MMPs), dentin matrix protein 1 (DMP-1), osteoblast/osteocyte factor 45 (OF45), Klotho, TGF-beta inducible factor (TIEG), lysophosphatidic acid (LPA), E11 antigen, and oxygen.
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The SAM domain is important for STIM oligomerization, since mutants in this domain lack the ability to form inducible punctae. Ca2+-binding experiments in vitro using human STIM1 EF–SAM (residue 58–201) or STIM2 EF–SAM (residue 149–292) fragments show that both isoforms bind Ca2+ with similar affinity (STIM2 Kd~0.5 mM; STIM1 Kd~0.2–0.6 mM), which is within the range of values reported for S/ER [Ca2+]. However, STIM2 differs from STIM1 in that it is already partially active at basal S/ER [Ca2+] and becomes fully activated earlier during S/ER store depletion. Despite the same Ca2+ affinity shown by STIM EF- SAM fragments, the full STIM2 protein showed a lower [Ca2+] sensitivity than STIM1 in transfected cells in vitro.
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Hypoxia also causes the upregulation of hypoxia-inducible factor 1 alpha (HIF1-α), which induces angiogenesis and is associated with poorer prognosis and the activation of genes associated with metastasis, leading, for instance, to increased cell migration and also ECM remodeling. While a lack of oxygen can cause glycolytic behavior in cells, some tumor cells also undergo aerobic glycolysis, in which they preferentially produce lactate from glucose even given abundant oxygen, called the Warburg effect. No matter the cause, this leaves the extracellular microenvironment acidic (pH 6.5–6.9), while the cancer cells themselves are able to remain neutral (ph 7.2–7.4) . It has been shown that this induces greater cell migration in vivo and in vitro, possibly by promoting degradation of the ECM.
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Further, Ratcliffe was able to modify other cells using the identified mRNA to give these cells oxygen- sensing capabilities. Building on these discoveries, the Ratcliffe group, along with joint studies with William Kaelin and Gregg Semenza, helped to uncover a detailed molecular chain of events that cells use to sense oxygen. A specific step identified was the binding of proteins expressed by the Von Hippel–Lindau tumor suppressor gene (VHL) to hypoxia-inducible factors (HIF), a transcription factor which trans-activates the EPO gene. Ratcliffe found that the VHL protein can bind a hydroxylated residues of HIF when oxygen is present at acceptable levels; the VHL protein then ubiquitylates the HIF protein which ultimately leads to the HIF protein's destruction.
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In addition to continuing descriptive studies of the effects of infection by defense mutualist endophytes, there has been a sharp increase in the number of studies which delve further into the ecology of plant-fungus associations and especially their multi-trophic impacts. The processes by which endophytic fungi alter plant physiology and volatile chemical levels are virtually unknown, and limited current results show a lack of consistency under differing environmental conditions, especially differing levels of herbivory. Studies comparing the relative impacts of mutualistic endophytes on inducible defenses and tolerance show a central function of infection in determining both responses to herbivore damage. On the whole, molecular mechanisms behind endophyte-mediated plant defense has been an increasing focus of research over the past ten years.
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Alcohol dehydrogenase and aldehyde dehydrogenase are present at their highest concentrations in the liver, but are widely expressed throughout the body, and alcohol dehydrogenase may also be present in the stomach and small intestine. Aside from alcohol dehydrogenase, the microsomal ethanol-oxidizing system (MEOS), specifically mediated by the cytochrome P450 enzyme CYP2E1, is the other major route of ethanol metabolism. CYP2E1 is inducible by ethanol, so while alcohol dehydrogenase handles acute or low concentrations of ethanol, MEOS is predominant with higher concentrations or with repeated/chronic use. A small amount of ethanol undergoes conjugation to form ethyl glucuronide and ethyl sulfate. There may also be another metabolic pathway that metabolizes as much as 25 to 35% of ethanol at typical concentrations.
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Some of these responses are governed by transcriptional control of the fast twitch (FT) glycolytic phenotype. For example, skeletal muscle reprogramming from an ST glycolytic phenotype to an FT glycolytic phenotype involves the Six1/Eya1 complex, composed of members of the Six protein family. Moreover, the hypoxia-inducible factor 1-α (HIF1A) has been identified as a master regulator for the expression of genes involved in essential hypoxic responses that maintain ATP levels in cells. Ablation of HIF-1α in skeletal muscle was associated with an increase in the activity of rate-limiting enzymes of the mitochondria, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway in these animals.
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Each cell typically contains several hundred of a special class of enhancers that stretch over many kilobases long DNA sequences, called "super-enhancers". These enhancers contain a large number of binding sites for sequence-specific, inducible transcription factors, and regulate expression of genes involved in cell differentiation. During inflammation, the transcription factor NF-κB facilitates remodeling of chromatin in a manner that selectively redistributes cofactors from high-occupancy enhancers, thereby repressing genes involved in maintaining cellular identify whose expression they enhance; at the same time, this F-κB-driven remodeling and redistribution activates other enhancers that guide changes in cellular function through inflammation. As a result, inflammation reprograms cells, altering their interactions with the rest of tissue and with the immune system.
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The functional TDRD7 protein inhibits the replication of SeV and other paramyxoviruses, suppressing autophagy, which is necessary for productive infection with these viruses. SeV also triggers the expression of IFN induced Ifit2 protein that is involved in protecting mice from SeV through as yet unknown mechanism. In addition, SeV triggers the expression of the chemokine interferon-γ inducible protein 10 kDa (CXCL10), which is involved in chemotaxis, induction of apoptosis, regulation of cell growth and mediation of angiostatic effects. Human mast cell infection with SeV induces expression of interferon-stimulated genes MxA Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity and IFIT3 in addition to activation of expression of type 1 IFN, MDA-5, RIG-1 and TLR-3.
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In 2014, Monteggia and her lab used a novel inducible knockout system to selectively knock out Brain-derived Neurotrophic Factor, a neurotrophin, in the forebrains of mice to explore the role of BDNF in complex behaviors. They found that depletion of BDNF impaired hippocampal learning and long-term potentiation and they further found that a loss of BDNF also impaired the effects of the antidepressant, desipramine. Monteggia’s group then showed that selective loss of BDNF in the dentate gyrus region of the hippocampus, but not the CA1 region, attenuates the effects of the antidepressants desipramine and citalopram during the forced swim test. Her findings suggest that the actions of antidepressants on specifically the dentate gyrus region of the hippocampus mediate their therapeutic effects.
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The inducible T-cell co-stimulator (CD278 or ICOS) is proven to provide a particularly critical signal for TFH cells since experimental mice deficient in ICOS are unable to develop any TFH. Additionally, it has been shown that ICOS induces the secretion of IL-21 cytokine by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH cells and germinal centers. Also Bcl-6 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has also been implicated in memory CD8+ T cell development. In germinal centers, antigen-experienced TFH cells rapidly upregulate the expression of CD40L, which binds and stimulates the B cell surface receptor CD40.
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Illustration of how cells sense and adapt to oxygen availability While a post-doctorate researcher at Johns Hopkins, Semenza evaluated gene expression in transgenic animals to determine how this affected the production of erythropoietin (EPO), known to be part of the means for the body to react to hypoxia, or low oxygen levels in the blood. Semenza identified the gene sequences that expressed hypoxia-inducible factors (HIF) proteins. Semenza's work showed that the HIF proteins consisted of two parts; HIF-1β, a stable base to most conditions, and HIF-1α that deteriorated when nominal oxygen levels were present. HIF-1α was further found essential to the EPO production process, as test subjects modified to be deficient in HIF-1α were found to have malformed blood vessels and decreased EPO levels.
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Like many cleverly named fly mutants, the name "naked cuticle" derives from the fact that mutants lack most of the hair-like protrusions from their ventral cuticle and thus appear "naked". In Drosophila, nkd is a segment-polarity class gene that limits the spatial extent of Wnt signaling pathway activity, similar to how the Patched (Ptc) gene regulates the Hedgehog signaling pathway; i.e., Nkd and Ptc shape tissue gradients of Wnt and Hedgehog signaling. Nkd was linked to Wnt signaling based on expansion of Wnt signaling in nkd mutants, by overexpression of Nkd mimicking loss of Wnt signaling,Zeng W, Wharton KA Jr, Mack JA, Wang K, Gadbaw M, Suyama K, Klein PS, Scott MP. naked cuticle encodes an inducible antagonist of Wnt signalling. Nature. 2000 Feb 17;403(6771):789-95.
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Wong and Licinio contributed some of the earliest work on the role of cytokines and immune mediators in the brain, with implications for the underlying biology of major depressive disorder, and published scientific articles on the localisation of gene expression for interleukin 1 receptor antagonist, interleukin 1 receptor, type I (IL1R1), also known as CD121a (Cluster of Differentiation 121a), and inducible nitric oxide synthase (iNOS) in mammalian brain. They also showed that interleukin 1 receptor antagonist is an endogenous neuroprotective agent. They have shown that the central and peripheral cytokine compartments are integrated but differentially regulated. In collaboration with colleagues at Columbia University Licinio and his team showed that inflammation-mediated up-regulation of secretory sphingomyelin phosphodiesterase in vivo represents a possible link between inflammatory cytokines and atherogenesis.
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Some proteins can be induced to form abnormal assemblies by exposure to the same (or similar) protein that has folded into a disease- causing conformation, a process called 'seeding' or 'permissive templating'. In this way, the disease state can be brought about in a susceptible host by the introduction of diseased tissue extract from an afflicted donor. The best known form of such inducible proteopathy is prion disease, which can be transmitted by exposure of a host organism to purified prion protein in a disease-causing conformation. There is now evidence that other proteopathies can be induced by a similar mechanism, including Aβ amyloidosis, amyloid A (AA) amyloidosis, and apolipoprotein AII amyloidosis, tauopathy, synucleinopathy, and the aggregation of superoxide dismutase-1 (SOD1), polyglutamine, and TAR DNA-binding protein-43 (TDP-43).
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Doxycycline and other members of the tetracycline class of antibiotics are often used as research reagents in in vitro and in vivo biomedical research experiments involving bacteria as well in experiments in eukaryotic cells and organisms with inducible protein expression systems using tetracycline-controlled transcriptional activation. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however protein translation is also disrupted in eukaryotic mitochondria impairing metabolism and leading to effects that can confound experimental results. Doxycycline is also used in "tet-on" (gene expression activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures. Doxycycline is more stable than tetracycline for this purpose.
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Expression of a mutant form of N-cadherin harboring a large deletion in the extracellular domain inhibited the function of endogenous N-cadherin in adult ventricular cardiomyocytes, and neighboring cardiomyocytes lost cell–cell contact and gap junction plaques as well. Mouse models employing transgenesis have highlighted the function of N-cadherin in cardiac muscle. Mice with altered expression of N-cadherin and/or E-cadherin showed a dilated cardiomyopathy phenotype, likely due to malfunction of intercalated discs. In agreement with this, mice with ablation of N-cadherin in adult hearts via a cardiac-specific tamoxifen- inducible Cre N-cadherin transgene showed disrupted assembly of intercalated discs, dilated cardiomyopathy, impaired cardiac function, decreased sarcomere length, increased Z-line thickness, decreases in connexin 43, and a loss in muscular tension.
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Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall.
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As mechanisms to dispose of both hydrogen peroxide and lipid hydroperoxides are essential to life, this indicates that in contrast to the multiple metabolic pathways that can be utilised to dispose of hydrogen peroxide, pathways for the disposal of lipid hydroperoxides are limited. While mammals have only one copy of the GPX4 gene, fish have two copies, GPX4a and GPX4b. The GPX4's appear to play a greater role in the fish GPX system than in mammals. For example, in fish GPX4 activity contributes to a greater extent to total GPX activity, GPX4a is the most highly expressed selenoprotein mRNA (in contrast to mammals where it is GPX1 mRNA) and GPX4a appears to be highly inducible to changes within the cellular environment, such as changes in methylmercury and selenium status.
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D-test When testing a gram-positive culture for sensitivity to clindamycin, it is common to perform a "D-test" to determine if there is a macrolide-resistant subpopulation of bacteria present. This test is necessary because some bacteria express a phenotype known as MLSB, in which susceptibility tests will indicate the bacteria are susceptible to clindamycin, but in vitro the pathogen displays inducible resistance. To perform a D-test, an agar plate is inoculated with the bacteria in question and two drug-impregnated disks (one with erythromycin, one with clindamycin) are placed 15–20 mm apart on the plate. If the area of inhibition around the clindamycin disk is "D" shaped, the test result is positive and clindamycin should not be used due to the possibility of resistant pathogens and therapy failure.
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Cells counterbalance the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX), which rely on the reducing power of NADPH to maintain their activities. Most risk factors associated with cancer interact with cells through the generation of ROS. ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB), activator protein-1 (AP-1), hypoxia-inducible factor-1α and signal transducer and activator of transcription 3 (STAT3), leading to expression of proteins that control inflammation; cellular transformation; tumor cell survival; tumor cell proliferation; and invasion, agiogenesis as well as metastasis. And ROS also control the expression of various tumor suppressor genes such as p53, retinoblastoma gene (Rb), and phosphatase and tensin homolog (PTEN).
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13-HODE, 13-oxoODE, and 13-EE-HODE (along with their 9-HODE counterparts) directly activate peroxisome proliferator- activated receptor gamma (PPARγ). This activation appears responsible for the ability of 13-HODE (and 9-HODE) to induce the transcription of PPARγ-inducible genes in human monocytes as well as to stimulate the maturation of these cells to macrophages. 13(S)-HODE (and 9(S)-HODE) also stimulate the activation of peroxisome proliferator-activated receptor beta (PPARβ) in a model cell system; 13-HODE (and 9-HODE) are also proposed to contribute to the ability of oxidized low-density lipoprotein (LDL) to activate PPARβl: LDL containing phospholipid-bound 13-HODE (and 9-HODE) is taken up by the cell and then acted on by phospholipases to release the HODEs which in turn directly activate PPARβl.
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Kaelin's research found that in VHL subjects, there were genes expressed the formation of a protein critical in the EPO process, but which the mutation suppressed. Kaelin's work aligned with that of Peter J. Ratcliffe and Gregg Semenza who separately had identified a two-part protein, hypoxia-inducible factors (HIF) that was essential to EPO production and which was triggered by oxygen levels in the blood. Kaelin's work found that the VHL protein would help regulate the HIF, and in subjects where the VHL proteins were not present, the HIF would overproduce EPO and lead to cancer. The combined work of Kaelin, Ratcliffe, and Semenza identified the pathway of how cells detect and react to oxygen levels in the blood, and have led to the development of drugs to help patients with anaemia and kidney failure.
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In July 2017, she took up the position of head of the Biochemistry Department in the Institute of Integrative Biology, and from 2020 has been promoted to become executive dean of the Institute of Systems, Molecular & Integrative Biology at the University of Liverpool. Rocha is an experienced undergraduate and postgraduate teacher and convenor, and has delivered courses on cell signalling, genes and cancer module, genes and proteins, and was a lecturer in gene regulation and expression modules at the University of Dundee, including module coordination. As of 2019, she has published >60 peer-reviewed research articles, co-authored 12 peer-reviewed research reviews and contributed to one book chapter. Amongst her most cited work is the discovery that Hypoxia- Inducible Factor is regulated by NF-κB and a recent paper in Science that demonstrates Hypoxia modulates histone methylation and reprograms chromatin.
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Klf4 also mediates the vascular response to nitric oxide (NO) by activating the promoters of inducible nitric oxide synthase (iNOS) in endothelial cells and cGMP-dependent protein kinase 1α/protein kinase G 1α (PKG 1α) in VSMCs. PKG 1α is activated by NO and mediates VSMC relaxation. This trans-activating effect of Klf4 on the PKG 1α promoter is inhibited by RhoA-induced actin polymerisation, possibly via G-actin regulation of a Klf4 co-activator or co- repressor. RhoA signalling pathways and RhoA activation are implicated in hypertension and increased vascular resistance which to some extent can be explained by this interaction with Klf4 and its effects on the response to NO. Klf5 has no effect on the PKG 1α promoter though the protein expression and nuclear localisation of Klf5 was similar to that of Klf4.
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During graduate school, Yapici explored the underlying genetic mechanisms of post-mating behavioral responses of female flies to understand, at a fundamental level, how an environmental influence can lead to a change in physiology and behavior. To answer her questions, Yapici and her colleagues developed a high throughout egg-laying assay such that they could observe receptivity and egg- laying behavior in virgin versus recently mated females. This allowed them to probe the genetic differences between a receptive female and a post-mated non- receptive female to understand what was leading to this change in mating behavior after copulation. Using an inducible RNAi library technique to genetically screen the female drosophila, they found many genes involved in egg-laying and mating behaviors and the genes that markedly stood out were the gene for sex peptide and the gene for sex peptide receptor.
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This is another large superfamily of CLRs that includes #The classic asialoglycoprotein receptor macrophage galactose-type lectin (MGL) #DC-SIGN (CLEC4L) #Langerin (CLEC4K) #Myeloid DAP12‑associating lectin (MDL)‑1 (CLEC5A) #DC‑associated C‑type lectin 1 (Dectin1) subfamily which includes ##dectin 1/CLEC7A ##DNGR1/CLEC9A ##Myeloid C‑type lectin‑like receptor (MICL) (CLEC12A) ##CLEC2 (also called CLEC1B)- the platelet activation receptor for podoplanin on lymphatic endothelial cells and invading front of some carcinomas. ##CLEC12B #DC immunoreceptor (DCIR) subfamily which includes: ##DCIR/CLEC4A ##Dectin 2/CLEC6A ##Blood DC antigen 2 (BDCA2) ( CLEC4C) ##Mincle i.e. macrophage‑inducible C‑type lectin (CLEC4E) The nomenclature (mannose versus asialoglycoprotein) is a bit misleading as these the asialoglycoprotein receptors are not necessarily galactose (one of the commonest outer residues of asialo-glycoprotein) specific receptors and even many of this family members can also bind to mannose after which the other group is named.
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In 2016, his team developed a novel compound, trans-dichloro oxovanadium(IV) complex of pyrenyl terpyridine, a visible light inducible DNA crosslinker which could be activated by visible light and it showed properties of forming crosslinks in the DNA when cancer cells are exposed to UV-A or visible light, thus protecting the cells against the onset of cancer. His studies have been documented by way of a number of articles and ResearchGate, an online repository of scientific articles has listed 38 of them. He has delivered invited speeches at several international conferences which included the seminar on Distinct roles of RAD51 paralogs in DNA damage responses held at Centre for DNA Fingerprinting and Diagnostics on 4 October 2016 and the Indo-French Conference on Recent Advances in Genome Integrity and Plasticity held at Bengaluru in December 2017. He also hosts several post-doctoral and doctoral researchers at his laboratory.
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However, defenses that animals have evolved are mostly general > rather than specific for particular chemicals; moreover, defenses are > generally inducible and therefore protect well from low doses of both > synthetic and natural chemicals. > 3) Because the toxicology of natural and synthetic chemicals is similar, > one expects (and finds) a similar positivity rate for carcinogenicity among > synthetic and natural chemicals. The positivity rate among chemicals tested > in rats and mice is ~50%. Therefore, because humans are exposed to so many > more natural than synthetic chemicals (by weight and by number), humans are > exposed to an enormous background of rodent carcinogens, as defined by high- > dose tests on rodents. We have shown that even though only a tiny proportion > of natural pesticides in plant foods have been tested, the 29 that are > rodent carcinogens among the 57 tested, occur in more than 50 common plant > foods.
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This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin organization, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins. HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive post-transcriptional modifications in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks.
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These genes function in concert with transcription factors, hypoxia inducible factors (HIF), which in turn are central mediators of red blood cell production in response to oxygen metabolism. Further, the Tibetans are enriched for genes in the disease class of human reproduction (such as genes from the DAZ, BPY2, CDY, and HLA-DQ and HLA-DR gene clusters) and biological process categories of response to DNA damage stimulus and DNA repair (such as RAD51, RAD52, and MRE11A), which are related to the adaptive traits of high infant birth weight and darker skin tone and, are most likely due to recent local adaptation. Among the Andeans, there are no significant associations between EPAS1 or EGLN1 and hemoglobin concentration, indicating variation in the pattern of molecular adaptation. However, EGLN1 appears to be the principal signature of evolution, as it shows evidence of positive selection in both Tibetans and Andeans.
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His focus in neuropsychopharmacology and molecular neuroscience concentrates on forming a molecular approach to psychiatry and furthering the understanding of the molecular basis of both depression and drug addiction, using animal models to study the way drug use or stress affects the brain. His addiction research largely centers around several transcription factors, including ΔFosB and CREB (master control proteins that induce addiction or depression in vulnerable individuals or resistance to these syndromes in resilient individuals) and the associated epigenetic remodeling that occurs in specific neuronal cell types in the brain. Among the prominent targets of this work are medium spiny neurons of the nucleus accumbens and pyramidal neurons in prefrontal cortex and ventral hippocampus. The Nestler laboratory has driven innovative use of viral-mediated gene transfer, inducible, cell-type specific mutations in mice, and locus-specific epigenome editing to establish causal links between molecular and behavioral phenomena in animal models.
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PEA reduces the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and prevents IkB-alpha degradation and p65 NF-kappaB nuclear translocation, the latter related to PEA as an endogenous PPAR-alpha agonist. In 2012 it became clear that PEA can also reduce reperfusion injury and the negative impact of shock on various outcome parameters, such as renal dysfunction, ischemic injury and inflammation, most probably via the PPAR-alpha pathway. Among the reperfusion and inflammation markers measured PEA could reduce the increase in creatinine, γGT, AST, nuclear translocation of NF-κBp65; kidney MPO activity and MDA levels, nitrotyrosine, PAR and adhesion molecules expression, the infiltration and activation of mastcells and apoptosis. The biological responses to PEA dosing in animal models and in humans are being investigated vis-à-vis its involvement in a repair mechanism relevant to patient conditions of chronic inflammation and chronic pain.
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9-HODE, 9-oxoODE, and 9-EE-HODE (along with their 13-HODE counterparts) directly activate peroxisome proliferator- activated receptor gamma (PPARγ).Cell. 1998 Apr 17;93(2):229-40Nat Struct Mol Biol. 2008 Sep;15(9):924-31Biol Pharm Bull. 2009 Apr;32(4):735-40 This activation appears responsible for the ability of 13-HODE (and 9-HODE) to induce the transcription of PPARγ-inducible genes in human monocytes as well as to stimulate the maturation of these cells to macrophages. 13(S)-HODE (and 9(S)-HODE) also stimulate the activation of peroxisome proliferator-activated receptor beta (PPARβ) in a model cell system; 13-HODE (and 9-HODE) are also proposed to contribute to the ability of oxidized low-density lipoprotein (LDL) to activate PPARβl: LDL containing phospholipid-bound 13-HODE (and 9-HODE) is taken up by the cell and then acted on by phospholipases to release the HODEs which in turn directly activate PPARβl.
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This research led Karczmar to conceptualize on the pre-neurogenetic appearance of components of the cholinergic system, their non-parallel ontogenesis and its significance, and their omni-existent phylogenesis which is independent of the presence of innervation or motility.Scudder and Karczmar, 1966also Karczmar, 1963 a and b Karczmar and Steve Thesleff demonstrated in the 1950s the phenomenon of desensitization (receptor inactivation) at the neuromyal junction, and Karczmar described the reciprocal process, sensitization which is inducible by several drugs such as oxamides and NaF, and which, today, is ascribed to an allosteric receptor change.Karczmar, 1957Karczmar and Howard, 1955 Karczmar pioneered also the studies of the structural nature of central cholinergic receptors by demonstrating the structural similarity between peripheral and central muscarinic receptors.Karczmar and Long, 1958 With Kyozo Koketsu, Syogoro Nishi and Nae Dun Karczmar identified in the 1950s and 1960s the three ganglionic receptor sites (nicotinic, muscarinic and peptidergic) and their potentials; they described their ionic mechanisms and the contribution of second messengers to ganglionic transmission.
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Studies have demonstrated that the oxidative stress generated by arsenic may disrupt the signal transduction pathways of the nuclear transcriptional factors PPARs, AP-1, and NF-κB, as well as the pro- inflammatory cytokines IL-8 and TNF-α. The interference of oxidative stress with signal transduction pathways may affect physiological processes associated with cell growth, metabolic syndrome X, glucose homeostasis, lipid metabolism, obesity, insulin resistance, inflammation, and diabetes-2. Recent scientific evidence has elucidated the physiological roles of the PPARs in the ω- hydroxylation of fatty acids and the inhibition of pro-inflammatory transcription factors (NF-κB and AP-1), pro-inflammatory cytokines (IL-1, -6, -8, -12, and TNF-α), cell4 adhesion molecules (ICAM-1 and VCAM-1), inducible nitric oxide synthase, proinflammatory nitric oxide (NO), and anti-apoptotic factors. Epidemiological studies have suggested a correlation between chronic consumption of drinking water contaminated with arsenic and the incidence of Type 2-diabetes.
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Through text mining, TMEM143 is shown to have interactions with seven different proteins in humans: Zinc finger protein 541 (ZNF541), DNA-damage inducible 1 homolog 2 (DD12), Paraneoplastic Ma antigen family-like 2 (PNMAL2), Kelch-like 31(JLHL31), Chromosome 14 open reading frame 28 (C14orf28), Chromosome 14 open reading frame 28 (TRIN71), and Cytoplasmic polyadenylation element binding protein 2 (CPEB). ZNF541 and PNMAL2, in relation to TMEM143, have been documented as having a role in the allelic loss of q13.3 of chromosome 19. This loss results in documented cases of malignant gliomas, neuroblastomas, and ovarian carcinomas, all suggesting a tumor suppression gene or genes in this region. While TMEM143 is not directly referred to in research in this area, it is present in this region on the chromosome, indicating a potential functional role in humans. Interactions between TMEM143 and DD12, JLHL31, C14orf28, TRIN71, and CPEB (in humans) have been documented through microarray data.
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As mentioned above, H. pylori produce large amounts of urease to produce ammonia as one of its adaptation methods to overcome stomach acidity. Helicobacter pylori arginase, a bimetallic enzyme binuclear Mn2-metalloenzyme arginase, crucial for pathogenesis of the bacterium in human stomach, a member of the ureohydrolase family, catalyzes the conversion of L-arginine to L-ornithine and urea, where ornithine is further converted into polyamines, which are essential for various critical metabolic processes. This provides acid resistance and is thus important for colonization of the bacterium in the gastric epithelial cells. Arginase of H. pylori also plays a role in evasion of the pathogen from the host immune system mainly by various proposed mechanisms, arginase competes with host-inducible nitric oxide (NO) synthase for the common substrate L-arginine, and thus reduces the synthesis of NO, an important component of innate immunity and an effective antimicrobial agent that is able to kill the invading pathogens directly.
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The algal CCM is inducible, and induction of the CCM is generally the result of low CO2 conditions. Induction and regulation of the Chlamydomonas CCM was recently studied by transcriptomic analysis, revealing that one out of three genes are up- or down-regulated in response to changed levels of CO2 in the environment.Brueggeman, A. J., Gangadharaiah, D. S., Cserhati, M. F., Casero, D., Weeks, D. P., & Ladunga, I. (2012). Activation of the carbon concentrating mechanism by CO2 deprivation coincides with massive transcriptional restructuring in Chlamydomonas reinhardtii. The Plant Cell, 24(5), 1860-1875 Sensing of CO2 in Chlamydomonas involves a “master switch”, which was co-discovered by two laboratories.Xiang, Y., Zhang, J., & Weeks, D. P. (2001). The Cia5 gene controls formation of the carbon concentrating mechanism in Chlamydomonas reinhardtii. Proceedings of the National Academy of Sciences, 98(9), 5341-5346 Fukuzawa, H., Miura, K., Ishizaki, K., Kucho, K. I., Saito, T., Kohinata, T., & Ohyama, K. (2001).
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Macrophages are remarkably plastic cells which in order to adapt to different tissue microenvironments can assume a range of different phenotypes. Accordingly, macrophages can exhibit either pro- or anti-inflammatory phenotypes and are routinely classified into M1 (classically activated) phenotype and M2 (alternatively activated) phenotype. According to this classification, macrophages acquire M1 phenotype following in vitro stimulation with interferon gamma (IFN-γ) alone or in combination with TLR ligands (e.g. lipopolysaccharide (LPS)) whereas macrophages acquire M2 phenotype after in vitro exposure to IL-4 and IL-13. M1 macrophages secrete high levels of proinflammatory cytokines (e.g. tumor necrosis factor (TNF-α), IL-6, IL-1β) and generate reactive oxygen and nitrogen species such as nitric oxide via activation of inducible nitric oxide synthase (iNOS). Conversely, M2 macrophages activate arginase 1 (Arg1) that blocks iNOS activity and therefore inhibits nitric oxide production. They also secrete anti-inflammatory cytokines (e.g. IL-10, TGF-β, IL-4) essential for inflammatory response resolution. M1 macrophages are microbicidal and tumoricidal, and stimulate adaptive immune response.
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Research in mammals has implicated hypoxia inducible factor (HIF) as a key regulator of gene expression changes in response to hypoxia However, a direct link between fish HIFs and gene expression changes in response to hypoxia has yet to be found. Phylogenetic analysis of available fish, tetrapod, and bird HIF-α and -β sequences shows that the isoforms of both subunits present in mammals are also represented in fish Within fish, HIF sequences group close together and are distinct from tetrapod and bird sequences. As well, amino acid analysis of available fish HIF-α and -β sequences reveals that they contain all functional domains shown to be important for mammalian HIF function, including the basic helix-loop- helix (bHLH) domain, Per-ARNT-Sim (PAS) domain, and the oxygen-dependent degradation domain (ODD), which render the HIF-α subunit sensitive to oxygen levels. The evolutionary similarity between HIF sequences in fish, tetrapods and birds, as well as the conservation of important functional domains suggests that HIF function and regulation is similar between fish and mammalian species.
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Base Substitutions in the capitalized nucleotides led to the greatest reduction in FLP-mediated site-specific recombination (Wildtype x mutant and mutant x mutant): ::5'3' Many available constructs include an additional arm sequences (5'--3') one base pair away from the upstream element and in the same orientation: ::5'3' This segment is dispensable for excision but essential for integration, including Recombinase-mediated cassette exchange. Because the recombination activity can be targeted to a selected organ, or a low level of recombination activity can be used to consistently alter the DNA of only a subset of cells, Flp-FRT can be used to construct genetic mosaics in multicellular organisms. Using this technology, the loss or alteration of a gene can be studied in a given target organ of interest, even in cases where experimental animals would not survive the loss of this gene in other organs (spatial control). The effect of altering a gene can also be studied over time, by using an inducible promoter to trigger the recombination activity late in development (temporal control) - this prevents the alteration.
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As such, RhoGDI2 could prove important in the regulation of tumor dormancy. Targeting this axis with orally available endothelin receptor antagonists may prove efficacious in mimicking the inhibitory role of RhoGDI2 by preventing macrophage infiltration into the micrometastatic niche. Recent work has also determined that genetic and pharmacologic targeting of chemokine (C-C motif) ligand 2 (CCL2) also known as monocyte chemotactic protein-1 (MCP-1) or small inducible cytokine A2, its receptor CCR2 and pharmacologic ablation of macrophages can also phenocopy the effect of RhoGDI2 expression to prevent metastatic colonization of the lung67 and that RhoGDI2 is suppressor of versican, a protein that has been shown to promote cell migration and metastasis in several tumor models. In contrast to its role as a metastasis suppressor in bladder cancer, in breast, RhoGDI2 expression has been reported to be upregulated in cancer and to promote invasion of breast cancer cells, while another report found a biphasic expression pattern of RhoGDI2 in breast cancer with decreased expression correlating with lymph node metastasis.
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Brown’s research is directed to the X-chromosome inactivation process in humans. Her lab has identified critical differences between mouse and human X-chromosome inactivation, such as the absence of paternal X inactivation in human extraembryonic tissues, the higher proportion of human “escapees” and the identification of different regulatory sequences of human XIST and mouse Xist. Her lab has been cataloging escape genes using both expression and DNA methylation analysis r to determine which genes contribute to sex differences in disease susceptibility, and which regions of DNA are susceptible to, or resistant to, epigenetic gene silencing. Since human embryonic stem cells are epigenetically unstable, Brown and colleagues have developed alternative model systems to study human inactivation, including inducible XIST transgenes in human somatic cells, human somatic cell hybrids retaining the active or the inactive X chromosome, and mouse cells with X-linked transgenes of human DNA. Her lab collaborates with other research groups at the B. C. Children’s Hospital and the BC Cancer Agency to investigate the clinical relevance of X-linked inactivation and expression in disease predisposition, cancer progression, and X-linked diseases, chromosome rearrangements and aneuploidies.
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IL-18 receptor consists of the inducible component IL-18Rα, which binds the mature IL-18 with low affinity and the constitutively expressed co-receptor IL-18Rβ. IL-18 binds the ligand receptor IL-18Rα, inducing the recruitment of IL-18Rβ to form a high affinity complex, which signals through the toll/interleukin-1 receptor (TIR) domain. This signaling domain rectruits MyD88 adaptor protein that activates proinflammatory programes and NF-κB pathway. The activity of IL-18 can be suppressed by extracellular interleukin 18 binding protein (IL-18BP) that binds soluble IL-18 with a higher affinity than IL-18Rα thus prevents IL-18 binding to IL-18 receptor. IL-37 is another endogenous factor that suppresses the action of IL-18. IL-37 has high homology with IL-18 and can bind to IL-18Rα, which then forms a complex with IL-18BP, thereby reduces the activity of IL-18. Moreover, IL-37 binds to single immunoglobulin IL-1 receptor related protein (SIGIRR), also known as IL-1R8 or TIR8, which forms a complex with IL-18Rα and induces an anti-inflammatory response. The IL-37/IL-18Rα/IL-1R8 complex activates the STAT3 signaling pathway, decreases NF-κB and AP-1 activation and reduces IFNγ production.
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