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Dependent Fashion (dependent + fashion)
Selected AbstractsGenes involved in the determination of the rate of inversions at short inverted repeatsGENES TO CELLS, Issue 6 2000Malgorzata M. Slupska Background Not all of the enzymatic pathways involved in genetic rearrangements have been elucidated. While some rearrangements occur by recombination at areas of high homology, others are mediated by short, often interrupted homologies. We have previously constructed an Escherichia coli strain that allows us to examine inversions at microhomologies, and have shown that inversions can occur at short inverted repeats in a recB,C -dependent fashion. Results Here, we report on the use of this strain to define genetic loci involved in limiting rearrangements on an F, plasmid carrying the lac genes. Employing mini-Tn10 derivatives to generate insertions near or into genes of interest, we detected three loci (rmuA,B,C) that, when mutated, increase inversions. We have mapped, cloned and sequenced these mutator loci. In one case, inactivation of the sbcC gene leads to an increase in rearrangements, and in another, insertions near the recE gene lead to an even larger increase. The third gene involved in limiting inversions, rmuC, has been mapped at 86 min on the E. coli chromosome and encodes a protein of unknown function with a limited homology to myosins, and some of the SMC (structural maintenance of chromosomes) proteins. Conclusions This work presents the first example of an anti-mutator role of the sbcC,D genes, and defines a new gene (rmuC) involved in DNA recombination. [source] A steroid hormone that extends the lifespan of Caenorhabditis elegansAGING CELL, Issue 1 2007Florence Broué Summary Removing the germline of Caenorhabditis elegans extends lifespan. This lifespan extension requires the nuclear receptor DAF-12 and the cytochrome P450 DAF-9, suggesting that a lipophilic hormone is involved. Here we show that C. elegans contains several hormonal steroids that are also present in humans, including pregnenolone (3,-hydroxy-pregn-5-en-20-one; PREG) and other pregnane and androstane derivatives. We find that PREG can extend the lifespan of C. elegans. Moreover, PREG levels rise when the germline is removed in a daf-9- dependent fashion. PREG extends the lifespan of germline-defective daf-9 mutants dramatically, but has no effect on daf-12 mutants. Thus, germline removal may extend lifespan, at least in part, by stimulating the synthesis of PREG. [source] Development and validation of the maximal electro-shock seizure model in dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007P. R. TERRITO The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 ± 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 ,g/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds. [source] Chronic Amiodarone Effects on Epicardial Conduction and Repolarization in the Isolated Porcine HeartPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2000DOMINIQUE LACROIX Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarizution dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio 5O female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 ±11 ms vs 288 ± 5 m.s at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio5O experiments, mean ARI was further prolonged (390 ±10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class HI antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential. [source] NAADP on the up in pancreatic beta cells,a sweet message?BIOESSAYS, Issue 5 2003Sandip Patel Pancreatic beta cells secrete insulin in response to elevated plasma glucose levels in a Ca2+ -dependent fashion. Released insulin may act on the beta cell itself to promote further insulin synthesis and release. Recent studies by Johnson and Misler,1 Masgrau et al.2 and Mitchell et al.3 provide strong evidence (1) for the existence of intracellular Ca2+ stores sensitive to NAADP, a potent Ca2+ -mobilizing messenger, and (2) that these Ca2+ stores are involved in both glucose- and insulin-mediated signal transduction. NAADP may therefore play an important role in controling secretion of insulin from pancreatic beta cells. BioEssays 25:430,433, 2003. © 2003 Wiley Periodicals, Inc. [source] Interferon-gamma is causatively involved in experimental inflammatory bowel disease in miceCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006R. Ito Summary Cytokines may be crucially involved in the pathogenesis of inflammatory bowel diseases (IBD), but it remains controversial whether interferon (IFN)-,, a typical proinflammatory cytokine, is an essential mediator to cause the disorders. In the present study, IFN-,,/, and wild-type (WT) C57BL/6 mice were fed 2·5% dextran sodium sulphate (DSS) in drinking water for 7 days, in order to investigate DSS-induced intestinal inflammation. The DSS-treated WT mice exhibited a robust production of IFN-, in the gut, a remarkable loss of body weight, as well as high rate of mortality (60%). In striking contrast, IFN-, deficient mice did not develop DSS-induced colitis, as indicated by the maintenance of body weight and survival rate of 100%. Severe intestinal inflammation was demonstrated exclusively in WT animals in terms of the shortening of the bowel as well as the elevation of the disease activity index, myeloperoxidase (MPO) activity and serum haptoglobin level. Histological study of DSS-treated WT intestine revealed disruption of mucosal epithelium and massive infiltration of inflammatory cells, while the organ from IFN-,,/, mice remained virtually normal in appearance. Enzyme-linked immunosorbent assay (ELISA) analyses indicated abundant production of three chemokines, i.e. monokine induced by interferon-, (MIG), interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1), in the DSS-irritated intestine of WT but not of IFN-,,/, mice. The present results demonstrate clearly that IFN-, plays indispensable roles in the initiation of DSS colitis, and some chemokines are produced in an IFN-,-dependent fashion. [source] | |||||||||||||