Cyclic AMP Response Element Modulator: Cyclic AMP response element modulator is a basic leucine zipper transcription factor that is regulated by CYCLIC AMP. It plays an important role in SPERMATID development in the mammalian TESTIS.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Multiple Sclerosis, Relapsing-Remitting: The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914)Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Multiple Sclerosis, Chronic Progressive: A form of multiple sclerosis characterized by a progressive deterioration in neurologic function which is in contrast to the more typical relapsing remitting form. If the clinical course is free of distinct remissions, it is referred to as primary progressive multiple sclerosis. When the progressive decline is punctuated by acute exacerbations, it is referred to as progressive relapsing multiple sclerosis. The term secondary progressive multiple sclerosis is used when relapsing remitting multiple sclerosis evolves into the chronic progressive form. (From Ann Neurol 1994;36 Suppl:S73-S79; Adams et al., Principles of Neurology, 6th ed, pp903-914)Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Spermatogenesis: The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA.Centrioles: Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder.Spermatids: Male germ cells derived from the haploid secondary SPERMATOCYTES. Without further division, spermatids undergo structural changes and give rise to SPERMATOZOA.Germ Cells: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.Pachytene Stage: The stage in the first meiotic prophase, following ZYGOTENE STAGE, when CROSSING OVER between homologous CHROMOSOMES begins.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Spermatocytes: Male germ cells derived from SPERMATOGONIA. The euploid primary spermatocytes undergo MEIOSIS and give rise to the haploid secondary spermatocytes which in turn give rise to SPERMATIDS.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.Activating Transcription Factor 1: An activating transcription factor that regulates expression of a variety of genes including C-JUN GENES and TRANSFORMING GROWTH FACTOR BETA2.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Molecular Biology: A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism.Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function.Agoraphobia: Obsessive, persistent, intense fear of open places.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Anxiety Disorders: Persistent and disabling ANXIETY.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Authorship: The profession of writing. Also the identity of the writer as the creator of a literary production.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Video Games: A form of interactive entertainment in which the player controls electronically generated images that appear on a video display screen. This includes video games played in the home on special machines or home computers, and those played in arcades.3' Flanking Region: The region of DNA which borders the 3' end of a transcription unit and where a variety of regulatory sequences are located.MoscowPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Glyceraldehyde-3-Phosphate Dehydrogenases: Enzymes that catalyze the dehydrogenation of GLYCERALDEHYDE 3-PHOSPHATE. Several types of glyceraldehyde-3-phosphate-dehydrogenase exist including phosphorylating and non-phosphorylating varieties and ones that transfer hydrogen to NADP and ones that transfer hydrogen to NAD.Glucosephosphate DehydrogenaseKnowledge Bases: Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).Glucosephosphate Dehydrogenase Deficiency: A disease-producing enzyme deficiency subject to many variants, some of which cause a deficiency of GLUCOSE-6-PHOSPHATE DEHYDROGENASE activity in erythrocytes, leading to hemolytic anemia.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC Inorganic salts of phosphoric acid.Para-Aortic Bodies: Small masses of chromaffin cells found near the SYMPATHETIC GANGLIA along the ABDOMINAL AORTA, beginning cranial to the superior mesenteric artery (MESENTERIC ARTERY, SUPERIOR) or renal arteries and extending to the level of the aortic bifurcation or just beyond. They are also called the organs of Zuckerkandl and sometimes called aortic bodies (not to be confused with AORTIC BODIES in the THORAX). The para-aortic bodies are the dominant source of CATECHOLAMINES in the FETUS and normally regress after BIRTH.Leukemia, Promyelocytic, Acute: An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Hematopoietic Stem Cell Transplantation: Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.

CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes. (1/246)

Previously, we have shown that nuclear extracts from cultured mouse keratinocytes induced to differentiate by increasing the levels of extra-cellular calcium contain Fra-1, Fra-2, Jun B, Jun D and c-Jun proteins that bind to the AP-1 DNA binding sequence. Despite this DNA binding activity, AP-1 reporter activity was suppressed in these cells. Here, we have detected the CREB family proteins CREB and CREMalpha as additional participants in the AP-1 DNA binding complex in differentiating keratinocytes. AP-1 and CRE DNA binding activity correlated with the induction of CREB, CREMalpha and ATF-1 and CREB phosphorylation at ser133 (ser133 phospho-CREB) in the transition from basal to differentiating keratinocytes, but the activity of a CRE reporter remained unchanged. In contrast, the CRE reporter was activated in the presence of the dominant-negative (DN) CREB mutants, KCREB and A-CREB, proteins that dimerize with CREB family members and block their ability to bind to DNA. The increase in CRE reporter activity in the presence of these mutants suggests that CRE-mediated transcriptional activity is suppressed in keratinocytes through protein-protein interactions involving a factor that dimerizes with the CREB leucine zipper. In experiments where the A-CREB mutant was co-transfected with an AP-1 reporter construct, transcriptional activity was also increased indicating that a CREB family member binds AP-1 sites and represses AP-1 transcriptional activity as well. Exogenous expression of the transcriptional repressor CREMalpha down-regulated both CRE and AP-1 reporters in keratinocytes suggesting that this factor may contribute to the suppression of AP-1 transcriptional activity observed in differentiating keratinocytes.  (+info)

Regulation of cAMP responsive element binding modulator isoforms in cultured rat ovarian granulosa cells. (2/246)

A pituitary glycoprotein hormone FSH stimulates ovarian granulosa cells to induce ovarian follicular development. In this study we identified rat ovarian genes that were rapidly induced by FSH in the cultured rat granulosa cells by means of subtraction cloning. Complementary DNA clones encoding cAMP responsive element binding modulator (CREM) were identified as one of the FSH inducible genes. Northern blotting and reverse transcription and polymerase chain reaction (RT-PCR) analyses revealed that only the repressor type of CREM gene products, ICER (inducible cAMP early repressor) isoforms, were induced by FSH treatment in cultured rat granulosa cells. The induction of ICER by FSH was mimicked by reagents known to increase intracellular cAMP levels, indicating that the induction is through cAMP and protein kinase A signal transduction system. Induction of ICER was also confirmed as the protein levels. Electrophoretic mobility shift assay of granulosa cell extracts with a radiolabeled double stranded oligonucleotide corresponding to somatostatin cAMP responsive element also revealed that only the ICER proteins were induced by FSH treatment, whereas levels of CREM proteins were nearly constant regardless of the FSH treatment. Our present study demonstrates that FSH-induced and cAMP-mediated induction and attenuation of transcriptional responses by CREM gene products may be a key mechanistic component for the granulosa cell differentiation and proliferation.  (+info)

Transcription factors in neuroendocrine regulation: rhythmic changes in pCREB and ICER levels frame melatonin synthesis. (3/246)

Neurotransmitter-driven activation of transcription factors is important for control of neuronal and neuroendocrine functions. We show with an in vivo approach that the norepinephrine cAMP-dependent rhythmic hormone production in rat pineal gland is accompanied by a temporally regulated switch in the ratio of a transcriptional activator, phosphorylated cAMP-responsive element-binding protein (pCREB), and a transcriptional inhibitor, inducible cAMP early repressor (ICER). pCREB accumulates endogenously at the beginning of the dark period and declines during the second half of the night. Concomitant with this decline, the amount of ICER rises. The changing ratio between pCREB and ICER shapes the in vivo dynamics in mRNA and, thus, protein levels of arylalkylamine-N-acetyltransferase, the rate-limiting enzyme of melatonin synthesis. Consequently, a silenced ICER expression in pinealocytes leads to a disinhibited arylalkylamine-N-acetyltransferase transcription and a primarily enhanced melatonin synthesis.  (+info)

Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. (4/246)

Ubiquitin-mediated proteolysis controls diverse physiological processes in eukaryotes. However, few in vivo targets of the mammalian Cdc34 and Rad6 ubiquitin-conjugating enzymes are known. A yeast-based genetic assay to identify proteins that interact with human Cdc34 resulted in three cDNAs encoding bZIP DNA binding motifs. Two of these interactants are repressors of cyclic AMP (cAMP)-induced transcription: hICERIIgamma, a product of the CREM gene, and hATF5, a novel ATF homolog. Transfection assays with mammalian cells demonstrate both hCdc34- and hRad6B-dependent ubiquitin-mediated proteolysis of hICERIIgamma and hATF5. This degradation requires an active ubiquitin-conjugating enzyme and results in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription. Consistent with these results, the endogenous ICER protein is elevated in cells which are null for murine Rad6B (mHR6B-/-) or transfected with dominant negative and antisense constructs of human CDC34. Based on the requirement for CREM/ICER and Rad6B proteins in spermatogenesis, we determined expression of Cdc34, Rad6B, CREM/ICER isoforms, and the Skp1-Cullin-F-box ubiquitin protein ligase subunits Cul-1 and Cul-2, which are associated with Cdc34 activity during murine testicular development. Cdc34, Rad6B, and the Cullin proteins are expressed in a developmentally regulated manner, with distinctly different patterns for Cdc34 and the Cullin proteins in germ cells. The Cdc34 and Rad6B proteins are significantly elevated in meiotic and postmeiotic haploid germ cells when chromatin modifications occur. Thus, the stability of specific mammalian transcription factors is the result of complex targeting by multiple ubiquitin-conjugating enzymes and may have an impact on cAMP-inducible gene regulation during both meiotic and mitotic cell cycles.  (+info)

Stress-induced stimulation of early growth response gene-1 by p38/stress-activated protein kinase 2 is mediated by a cAMP-responsive promoter element in a MAPKAP kinase 2-independent manner. (5/246)

The p38/stress-activated protein kinase2 (p38/SAPK2) is activated by cellular stress and proinflammatory cytokines. Several transcription factors have been reported to be regulated by p38/SAPK2, and this kinase is involved in the control of expression of various genes. In human Jurkat T-cells, induction of the early growth response gene-1 (egr-1) by anisomycin is completely inhibited by SB203580, a specific inhibitor of p38/SAPK2a and -b. Northern blot and reporter gene experiments indicate that this block is at the level of mRNA biosynthesis. Using mutants of the egr-1 promoter, we demonstrate that a distal cAMP-responsive element (CRE; nucleotides -134 to -126) is necessary to control egr-1 induction by p38/SAPK2. Pull-down assays indicate that phospho-CRE binding protein (CREB) and phospho-activating transcription factor-1 (ATF1) bind to this element in a p38/SAPK2-dependent manner. In response to anisomycin, two known CREB kinases downstream to p38/SAPK2, MAPKAP kinase 2 (MK2) and mitogen- and stress-activated kinase 1 (MSK1), show increased activity. However, in MK2 -/- fibroblasts derived from mice carrying a disruption of the MK2 gene, the phosphorylation of CREB and ATF1 and the expression of egr-1 reach levels comparable with wild type cells. This finding excludes MK2 as an involved enzyme. We conclude that egr-1 induction by anisomycin is mediated by p38/SAPK2 and probably by MSK1. Phosphorylated CREB and ATF1 then bind to the CRE of the egr-1 promoter and cause a stress-dependent transcriptional activation of this gene.  (+info)

The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID. (6/246)

We analyzed a mechanism of transcriptional regulation of the human insulin gene by cyclic AMP response element modulator (CREM) through four cyclic AMP response elements (CREs). We isolated two novel CREM isoforms (CREMDeltaQ1 and CREMDeltaQ2), which lack one of the glutamine-rich domains, Q1 and Q2 respectively, and six known isoforms (CREMtaualpha, CREMalpha, inducible cyclic AMP early repressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and the RINm5F pancreatic beta-cell line. CREM isoforms functioned as efficient transcriptional activators or repressors to modulate insulin promoter activity by binding to all of the insulin CREs. The binding activity of repressors is higher than that of activators and suppressed not only basal activity but also activator-induced activities. Furthermore, CREM activator interacted directly with the transcription factor IID components hTAF(II)130 and TATA box-binding protein (TBP). These results suggest that the activation of the insulin gene transcription by CREM activator is mediated by not only direct binding to the CREs but also by recruiting transcription factor IID to the insulin promoter via its interaction with hTAF(II)130 and TBP. On the other hand, the CREM repressor ICER competitively interrupts the binding of the activators to CREs and does not interact with either TBP or hTAF(II)130; therefore, it might fail to stabilize the basal transcriptional machinery and repress transactivation.  (+info)

A novel 14-base-pair regulatory element is essential for in vivo expression of murine beta4-galactosyltransferase-I in late pachytene spermatocytes and round spermatids. (7/246)

During murine spermatogenesis, beginning in late pachytene spermatocytes, the beta4-galactosyltransferase-I (beta4GalT-I) gene is transcribed from a male germ cell-specific start site. We had shown previously that a 796-bp genomic fragment that flanks the germ cell start site and contains two putative CRE (cyclic AMP-responsive element)-like motifs directs correct male germ cell expression of the beta-galactosidase reporter gene in late pachytene spermatocytes and round spermatids of transgenic mice (N. L. Shaper, A. Harduin-Lepers, and J. H. Shaper, J. Biol. Chem. 269:25165-25171, 1994). We now report that in vivo expression of beta4GalT-I in developing male germ cells requires an essential and previously undescribed 14-bp regulatory element (5'-GCCGGTTTCCTAGA-3') that is distinct from the two CRE-like sequences. This cis element is located 16 bp upstream of the germ cell-specific start site and binds a male germ cell protein that we have termed TASS-1 (transcriptional activator in late pachytene spermatocytes and round spermatids 1). The presence of the Ets signature binding motif 5'-GGAA-3' on the bottom strand of the TASS-1 sequence (underlined sequence) suggests that TASS-1 is a novel member of the Ets family of transcription factors. Additional transgenic analyses established that an 87-bp genomic fragment containing the TASS-1 regulatory element was sufficient for correct germ cell-specific expression of the beta-galactosidase reporter gene. Furthermore, when the TASS-1 motif was mutated by transversion, within the context of the original 796-bp fragment, transgene expression was reduced 12- to 35-fold in vivo.  (+info)

Inducible cyclic AMP early repressor protein in rat pinealocytes: a highly sensitive natural reporter for regulated gene transcription. (8/246)

Rhythmic activity of arylalkylamine N-acetyltransferase (AANAT) determines melatonin synthesis in rat pineal gland. The transcriptional regulation of AANAT involves the activating and inhibiting transcription factors of the cyclic AMP (cAMP)-signaling pathway, cAMP response element-binding protein and inducible cAMP early repressor (ICER), respectively. Activation of this pathway is centered around norepinephrine, stimulating beta(1)-adrenergic receptors, but various other transmitters can modulate melatonin biosynthesis. To compare the transcriptional impact of norepinephrine with that of other neurotransmitters on melatonin synthesis, we determined ICER protein levels in pinealocytes and, in parallel, hormone secretion. The dose-dependent inductions of ICER protein by norepinephrine, the beta(1)-adrenergic receptor agonist isoproterenol, vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and adenosine are correlated to regulatory dynamics in melatonin production. Importantly, ICER protein induction required lower ligand concentrations than the induction of melatonin biosynthesis. Although neuropeptide Y, glutamate, and vasopressin altered norepinephrine-stimulated hormone production without affecting ICER levels, the activation of voltage-gated cation channels increased ICER without affecting hormone synthesis. Sensitivity and versatility of ICER induction in pinealocytes make these neuroendocrine cells a valuable model system in which to study molecular interactions determining a regulated gene expression.  (+info)

  • Finally, we found that PGE2 stimulated the expression of the inducible cyclic AMP early repressor, which appears to directly inhibit RALDH expression in DCs, thus providing mechanistic insight into how PGE2 signaling down-modulates RALDH. (
  • The presence of intracellular kinase inhibitor Belinostat Ca2 is required for E2 mediated dopamine efflux Although we have controlled for dopamine flux specifi cally through the DAT through the use of DAT and nore pinephrine selective transporter inhibitors, the addition of these inhibitors does not account for the possibility of exocytotic release of dopamine which is dependent on extracellular Inhibitors,Modulators,Libraries Ca2. (
  • The transduction of extracellular signals to intracellular responses is one of the most important and complicated aspects of cellular life. (
  • Our results demonstrate how cross-talk between signal dependent and lineage determining factors promotes the expression of cell type-specific gene programs in response to extracellular cues. (
  • Royal JM, Oh YJ, Grey MJ, Lencer WI, Ronquillo N, Galandiuk S, Matoba N. A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair via an unfolded protein response. (
  • The production of retinoic acid (RA) by dendritic cells (DCs) is critical for the induction of gut-tropic immune responses by driving the expression of intestinal-specific homing receptors, such as α4β7 and CCR9, upon T and B cell activation. (
  • Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. (
  • Although the different levels of dietary fish and vegetable oils involved in this study affected the expression of some transcripts, the immune-related pathways and functions activated by the antiviral response of salmon MLCs in both groups were comparable overall. (
  • The invention provides an expression system for producing Caveolin-1 in neuronal cells or neural stem cells comprising a neuron-specific regulatory element and a nucleic acid sequence encoding Caveolin-1. (
  • 20. The expression system of claim 1, wherein the neuron-specific regulatory element is the synapsin promoter as set forth in FIG. 8 beginning at position 7 and ending at position 488. (
  • Compared to preceding analyses, our novel approach integrated three types of omics information which includes gene Inhibitors,Modulators,Libraries expression information, MicroRNA expression data and ChIP seq information, which could execute cross validation one another with the systems biology level, and consequently the strategy is the two feasible and necessary to lower the discrepancy and strengthen the understanding with the complicated molecular mechanisms underlying cancer. (
  • The qPCR of these Inhibitors,Modulators,Libraries samples indicated that expression of each EGFR and ERBB3 at first greater for the duration of PCMO gen eration reaching a peak over the 2nd day and over the fourth day of culture and decreased thereafter. (
  • Women have stronger immune responses to infections and vaccination than men. (
  • Paradoxically, the stronger immune response comes at a steep price, which is the high incidence of autoimmune diseases in women. (
  • Besides gender, sex hormones contribute to the development and activity of the immune system, accounting for differences in gender-related immune responses. (
  • This review focuses on the role of sex hormones particularly estrogen, in the adaptive immune response, in health, and autoimmune disease with an emphasis on systemic lupus erythematosus. (
  • Intriguingly, the same immune response shifts during pregnancy to "tolerate" the foreign fetus and prevent rejection. (
  • There is evidence that there are differences in the immune response in the male seahorse during the parental vs. mating phases with improved immunity during the parental stage ( 1 , 2 ). (
  • A "side-effect" of the stronger immune response is the higher propensity for developing autoimmune disease. (
  • Sex hormones not only control the reproductive system, but also regulate the development, and function of the immune response. (
  • Innate and adaptive, humoral and cell-mediated immune responses are impacted by hormones, and dysregulation of these mechanisms contribute to immune-mediated diseases including autoimmune disease ( 3 - 9 ). (
  • It has been known for some time that sex hormones influence the function and activity of the immune system and likely contribute to the sex-based differences in immune-mediated disease responses. (
  • In general, these effects have resulted in adult females inducing a more efficient humoral-based immune response upon pathogen challenge, whereas males tend to mount a less efficient immune response [ 1 , 2 ]. (
  • Given the role of PGE2 in regulating the development of RA-producing DCs, modulating this pathway may prove a novel means to control the development of gut-tropic immune responses. (
  • A heterodimeric cytokine that plays a role in innate and adaptive immune responses. (
  • Fatty acids, notably polyunsaturated fatty acids (PUFAs), play an important role in innate immune responses and the functions of immune cells (e.g. (
  • AMP is used as a dietary supplement to boost immune activity, and is also used as a substitute sweetener to aid in the maintenance of a low-calorie diet. (
  • Nucleotides such as Adenosine-5'-Monophosphate affect a number of immune functions, including the reversal of malnutrition and starvation-induced immunosuppression, the enhancement of T-cell maturation and function, the enhancement of natural killer cell activity, the improvement of delayed cutaneous hypersensitivity, helping resistance to such infectious agents as Staphylococcus aureus and Candida albicans, and finally the modulation of T-cell responses toward type 1 CD4 helper lymphocytes or Th1 cells. (
  • Inactivating mutations introduced at the A4/A3 elements, binding sites for the glucose-regulated homeodomain transcription factor PDX-1, did not diminish the response to Ex-4, although a marked reduction of basal promoter activity was observed. (
  • We investigated the effects of mutating these -170 CRE and -150 CCAAT elements on the promoter activity regulated by three different modulators previously known to act through CRE: ATF-2, cAMP and E1a. (
  • Brain-derived neurotrophic factor ( BDNF ) is a central mediator of neuroplasticity, a term used to describe the ability of neurons to adapt in response to challenges, resulting in structural and functional changes to neurons (Huang et al, 2001). (
  • The high number of articles published (more than one hundred manuscripts for 14 botanicals) supports the growing interest in the use of natural products as BDNF modulators. (
  • The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. (
  • Additionally, there is evidence that glucocorticoids reduce BDNF, further linking the inflammatory response to neurotrophin levels (Gubba et al, 2004). (
  • 25-Dihydroxyvitamin D3 injection also abolished the effects of exercise on the consummate end-products of brain-derived neurotrophic factor action, i.e. cyclic AMP response element-binding protein and synapsin I, and modulated phosphorylated calmodulin protein kinase II, a signal transduction cascade downstream to brain-derived neurotrophic factor action that is important for learning and memory. (
  • AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. (
  • We infused 1,25-dihydroxyvitamin D3, a modulator of energy metabolism, directly into the hippocampus during 3 days of voluntary wheel running and measured its effects on brain-derived neurotrophic factor-mediated synaptic plasticity. (
  • Our results reveal a fundamental mechanism by which key elements of energy metabolism may modulate the substrates of hippocampal synaptic plasticity. (
  • We and others have shown that SLE T cells display decreased capacity to produce IL-2, a cytokine crucial to the development of cytotoxic responses, regulatory T-cell function and activation-induced cell death (13). (
  • LPLI also suppresses the inflammatory response of LPS-induced inflammation of stem cells. (