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Regulatory Signals (regulatory + signal)
Selected AbstractsThe type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Tania Vitalis Abstract In the rodent and human embryonic brains, the cerebral cortex and hippocampus transiently express high levels of type 1 cannabinoid receptors (CB1Rs), at a developmental stage when these areas are composed mainly of glutamatergic neurons. However, the precise cellular and subcellular localization of CB1R expression as well as effects of CB1R modulation in this cell population remain largely unknown. We report that, starting from embryonic day 12.5, CB1Rs are strongly expressed in both reelin-expressing Cajal-Retzius cells and newly differentiated postmitotic glutamatergic neurons of the mouse telencephalon. CB1R protein is localized first to somato-dendritic endosomes and at later developmental stages it localizes mostly to developing axons. In young axons, CB1Rs are localized both to the axolemma and to large, often multivesicular endosomes. Acute maternal injection of agonist CP-55940 results in the relocation of receptors from axons to somato-dendritic endosomes, indicating the functional competence of embryonic CB1Rs. The adult phenotype of CB1R expression is established around postnatal day 5. By using pharmacological and mutational modulation of CB1R activity in isolated cultured rat hippocampal neurons, we also show that basal activation of CB1R acts as a negative regulatory signal for dendritogenesis, dendritic and axonal outgrowth, and branching. Together, the overall negative regulatory role in neurite development suggests that embryonic CB1R signaling may participate in the correct establishment of neuronal connectivity and suggests a possible mechanism for the development of reported glutamatergic dysfunction in the offspring following maternal cannabis consumption. [source] Transcriptional regulation of transport and utilization systems for hexuronides, hexuronates and hexonates in gamma purple bacteriaMOLECULAR MICROBIOLOGY, Issue 4 2000Dmitry A. Rodionov The comparative approach is a powerful tool for the analysis of gene regulation in bacterial genomes. It can be applied to the analysis of regulons that have been studied experimentally as well as that of regulons for which no known regulatory sites are available. It is assumed that the set of co-regulated genes and the regulatory signal itself are conserved in related genomes. Here, we use genomic comparisons to study the regulation of transport and utilization systems for sugar acids in gamma purple bacteria Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, Yersinia pestis, Erwinia chrysanthemi, Haemophilus influenzae and Vibrio cholerae. The variability of the operon structure and the location of the operator sites for the main transcription factors are demonstrated. The common metabolic map is combined with known and predicted regulatory interactions. It includes all known and predicted members of the GntR, UxuR/ExuR, KdgR, UidR and IdnR regulons. Moreover, most members of these regulons seem to be under catabolite repression mediated by CRP. The candidate UxuR/ExuR signal is proposed, the KdgR consensus is extended, and new operators for all transcription factors are identified in all studied genomes. Two new members of the KdgR regulon, a hypothetical ATP-dependent transport system OgtABCD and YjgK protein with unknown function, are detected. The former is likely to be the transport system for the products of pectin degradation, oligogalacturonides. [source] The Langerhans' cell-like cell lines XS52 and XS106 express mRNA for ciliary neurotrophic factor and neurotrophic factor 4/5EXPERIMENTAL DERMATOLOGY, Issue 9 2004K. Seiffert Neurotrophins are responsible for the survival and outgrowth of nerves within the peripheral and central nervous systems. These factors include brain-derived neurotrophic factor (BDNF), CNTF, NT 3, and NT4/5. We have previously shown that LCs lie in close proximity to nerves and that several neuropeptides regulate LC function, implying that nerves send regulatory signals to LCs. To evaluate the possibility that LC signal nerves by release of neurotrophins, we examined LC expression of neurotrophins by RT-PCR. To eliminate the possibility of contaminating keratinocytes in highly enriched LC preparations, we utilized the LC-like cell lines XS52 (BALB/c derived) and XS106 (A/J derived) for initial experiments. The RNA obtained was digested with DNase to ensure complete absence of genomic DNA. Several independent RT-PCRs revealed expression of bands of the expected size for CTNF and NT4/5, but not for BDNF and NT3 in XS106 and XS52 cells. In contrast, the transformed keratinocyte cell line PAM212 expressed BDNF, as well as CTNF and NT4/5. Preliminary experiments with purified LC confirm the expression of CTNF and NT4/5 and also show the expression of BDNF. However, we cannot be sure that BDNF expression is not due to keratinocyte contamination. We conclude that LCs may regulate nerve cells by the release of neurotrophic factors. [source] BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Functional aspects of ribosomal architecture: symmetry, chirality and regulationJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2004Raz Zarivach Abstract High-resolution structures of both ribosomal subunits revealed that most stages of protein biosynthesis, including decoding of genetic information, are navigated and controlled by the elaborate ribosomal architectural-design. Remote interactions govern accurate substrate alignment within a flexible active-site pocket [peptidyl transferase center (PTC)], and spatial considerations, due mainly to a universal mobile nucleotide, U2585, ensure proper chirality by interfering with D -amino-acids incorporation. tRNA translocation involves two correlated motions: overall mRNA/tRNA (messenger and transfer RNA) shift, and a rotation of the tRNA single-stranded aminoacylated-3, end around the bond connecting it with the tRNA helical-regions. This bond coincides with an axis passing through a sizable symmetry-related region, identified around the PTC in all large-subunit crystal structures. Propelled by a bulged universal nucleotide, A2602, positioned at the two-fold symmetry axis, and guided by a ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry optimal for peptide-bond formation and in geometry ensuring nascent proteins entrance into their exit tunnel. Hence, confirming that ribosomes contribute positional rather than chemical catalysis, and that peptide bond formation is concurrent with A- to P-site tRNA passage. Connecting between the PTC, the decoding center, the tRNA entrance and exit points, the symmetry-related region can transfer intra-ribosomal signals between remote functional locations, guaranteeing smooth processivity of amino acids polymerization. Ribosomal proteins are involved in accurate substrate placement (L16), discrimination and signal transmission (L22) and protein biosynthesis regulation (CTC). Residing on the exit tunnel walls near its entrance, and stretching to its opening, protein-L22 can mediate ribosome response to cellular regulatory signals, since it can swing across the tunnel, causing gating and elongation arrest. Each of the protein CTC domains has a defined task. The N -terminal domain stabilizes the intersubunit-bridge confining the A-site-tRNA entrance. The middle domain protects the bridge conformation at elevated temperatures. The C -terminal domain can undergo substantial conformational rearrangements upon substrate binding, indicating CTC participation in biosynthesis-control under stressful conditions. Copyright © 2004 John Wiley & Sons, Ltd. [source] S -Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol With a Folate-Deficient DietALCOHOLISM, Issue 7 2007Farah Esfandiari Background: To demonstrate a causative role of abnormal methionine metabolism in the pathogenesis of alcoholic steatosis, we measured the effects on hepatic lipid synthesis of supplementing ethanol and folate-deficient diets with S -adenosylmethionine (SAM), a metabolite that regulates methionine metabolism. Methods: Yucatan micropigs were fed folate-deficient diets as control, with ethanol at 40% of kcal, and with ethanol supplemented with SAM at 0.4 g/1,000 kcal for 14 weeks. Histopathology, triglyceride levels and transcripts, and protein levels of the regulatory signals of hepatic lipid synthesis were measured in terminal omental adipose and liver samples. Results: Feeding ethanol at 40% of kcal with folate-deficient diets for 14 weeks increased and supplemental SAM maintained control levels of liver and plasma triglyceride. Serum adiponectin, liver transcripts of adiponectin receptor-1 (AdipoR1), and phosphorylated adenosine monophosphate kinase- , (p-AMPK,) were each reduced by ethanol feeding and were sustained at normal levels by SAM supplementation of the ethanol diets. Ethanol feeding activated and SAM supplementation maintained control levels of ER stress-induced transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) and its targeted transcripts of lipid synthesizing enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT). Conclusions: Ethanol feeding with a folate-deficient diet stimulates hepatic lipid synthesis by down-regulating adiponectin-mediated pathways of p-AMPK to increase the expression of nSREBP-1c and its targeted lipogenic enzymes. Preventing abnormal hepatic methionine metabolism by supplementing ethanol diets with SAM reduces liver triglyceride levels by up-regulation of adiponectin-mediated pathways to decrease fatty acid and triglyceride synthesis. This study demonstrates that ethanol-induced hepatic lipid synthesis is mediated in part by abnormal methionine metabolism, and strengthens the concept that altered methionine metabolism plays an integral role in the pathogenesis of steatosis. [source] Dentin matrix proteins and soluble factors: intrinsic regulatory signals for healing and resorption of dental and periodontal tissues?ORAL DISEASES, Issue 2 2004TA Silva Dentin contains numerous polypeptides and signaling molecules sequestered in a mineralized matrix. The exposure and release of these molecules occur as a consequence of injury to the pulp and periodontal ligament, which may result from luxation, orthodontic movement or infections of tooth and periodontal structures. When released at these sites, dentin constituents have the potential to act on different surrounding cells, including periodontal cells, osteoblasts, osteoclasts and inflammatory cells, and to affect the course of dental disease. Experimental studies have highlighted the interactions between dentin and cells from tooth and periodontal tissues and reveal dentin to be a cell adhesive, signaling and migratory stimulus for various mesenchymal and inflammatory cells. These results support the hypothesis that dentin molecules might function as regulatory signals for the healing and resorption of dental and periodontal tissues. Data from recent and classical investigations are summarized, many open questions are discussed, and current hypotheses concerning the mechanisms of tooth resorption and periodontal healing are outlined. Many questions regarding the importance of dentin as a source of multifunctional molecules remain unanswered and provide important directions for future studies. 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