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91.
Sherin Antony Peeyush Kumar T Jobin Mathew TR Anju CS Paulose 《Journal of biomedical science》2010,17(1):7
Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH and C + IIH). α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar dysfunction associated with hypoglycemia. 相似文献
92.
93.
Reutter D Schutzer SE Craft CM Fletcher J Fricke FL Holowachuk SA Johnson RC Keim PS Pearson JL Sibert RW Velsko S 《Biosecurity and bioterrorism : biodefense strategy, practice, and science》2010,8(4):343-355
A forensic capability to help identify perpetrators and exclude innocent people should be an integral part of a strategy against terrorist attacks. Exercises have been conducted to increase our preparedness and response capabilities to chemical, biological, radiological, and nuclear (CBRN) terrorist attacks. However, incorporating forensic components into these exercises has been deficient. CBRN investigations rely on forensic results, so the need to integrate a forensic component and forensics experts into comprehensive exercises is paramount. This article provides guidance for planning and executing exercises at local, state, federal, and international levels that test the effectiveness of forensic capabilities for CBRN threats. The guidelines presented here apply both to situations where forensics is only a component of a more general exercise and where forensics is the primary focus of the exercise. 相似文献
94.
Chilamakuri CS Reddy Sane Sudha Rani Bernard Offmann R Sowdhamini 《BMC research notes》2010,3(1):1-10
Background
Stem cell factor (SCF) receptor c-Kit is recognized as a key signaling molecule, which transduces signals for the proliferation, differentiation and survival of stem cells. Binding of SCF to its receptor triggers transactivation, leading to the recruitment of kinases and phosphatases to the docking platforms of c-Kit catalytic domain. Tyrosine phosphatase-1 (Shp-1) deactivates/attenuates 'Kit' kinase activity. Whereas, Asp816Val mutation in the Kit activation loop transforms kinase domain to a constitutively activated state (switch off-to-on state), in a ligand-independent manner. This phenomenon completely abrogates negative regulation of Shp-1. To predict the possible molecular basis of interaction between c-Kit and Shp-1, we have performed an in silico protein-protein docking study between crystal structure of activated c-Kit (phosphorylated c-Kit) and full length crystal structure of Shp-2, a close structural counterpart of Shp-1.Findings
Study revealed a stretch of conserved amino acids (Lys818 to Ser821) in the Kit activation domain, which makes decisive H-bonds with N-sh2 and phosphotyrosine binding pocket residues of the phosphatase. These H-bonds may impose an inhibitory steric hindrance to the catalytic domain of c-Kit, there by blocking further interaction of the activation loop molecules with incoming kinases. We have also predicted a phosphotyrosine binding pocket in SH2 domains of Shp-1, which is found to be predominantly closer to a catalytic groove like structure in c-Kit kinase domain.Conclusions
This study predicts that crucial hydrogen bonding between N-sh2 domain of Shp-1 and Kit activation loop can modulate the negative regulation of c-Kit kinase by Shp-1. Thus, this finding is expected to play a significant role in designing suitable gain-of-function c-Kit mutants for inducing conditional proliferation of hematopoietic stem cells. 相似文献95.
Inhibition of the human cytomegalovirus UL97 kinase by maribavir is thought to be responsible for the antiviral activity of this compound. Some mutations that confer resistance to maribavir map to UL97, however additional mutations that also confer resistance to the drug were mapped to UL27. These open reading frames share a low level of homology, yet the function of pUL27 remains unknown. A recombinant virus with a deletion in the UL27 open reading frame was reported previously to exhibit a slight replication deficit, but a more important function in vivo was hypothesized given its homology to the UL97 kinase. The potential for an important function in vivo was investigated by determining if these knockout viruses could replicate in human tissue implanted in SCID mice. None of the AD169 derived viruses replicated well in the implanted thymus/liver tissue, and is consistent with previous observations, although all of the viruses replicated to some degree in retinal tissue implants. Replication of the parent viruses was observed at 7 days post inoculation, whereas no replication was detected with any of the recombinant viruses with deletions in UL27. By day 14, replication was detected in two of the three knockout viruses and in all of the viruses by day 42. These data are consistent with minimal defects observed in cell culture, but are not consistent with an important role for UL27 in vivo. We conclude that UL27 is not required for viral replication in vivo. 相似文献
96.
97.
We propose a method based on parametric survival analysis to analyze step-stress data. Step-stress studies are failure time studies in which the experimental stressor is increased at specified time intervals. While this protocol has been frequently employed in industrial reliability studies, it is less common in the life sciences. Possible biological applications include experiments on swimming performance of fish using a step function defining increasing water velocity over time, and treadmill tests on humans. A likelihood-ratio test is developed for comparing the failure times in two groups based on a piecewise constant hazard assumption. The test can be extended to other piecewise distributions and to include covariates. An example data set is used to illustrate the method and highlight experimental design issues. A small simulation study compares this analysis procedure to currently used methods with regard to type I error rate and power. 相似文献
98.
Despite the differences in the response of male Betta splendens toward various stimuli, no research has attempted to determine the preference for a live conspecific versus a mirror presentation. A submerged T-maze was used to present both stimuli to healthy male B. splendens (N=16). The results indicated that subjects' start box and swimway latencies decreased significantly over the 30 trials. Moreover, the analysis of choices demonstrated a modest, but statistically significant, preference for the live conspecific over the mirror presentation. The results are discussed in terms of the stimuli qualities that elicit an aggressive response in B. splendens and the implications for common experimental procedures. 相似文献
99.
Ashley MV Wilk JA Styan SM Craft KJ Jones KL Feldheim KA Lewers KS Ashman TL 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2003,107(7):1201-1207
The objectives of the present study were to develop microsatellite markers for the wild strawberry, Fragaria virginiana, to evaluate segregation patterns of microsatellite alleles in this octoploid species, and assess genetic variability at microsatellite loci in a wild population. A genomic library was screened for microsatellite repeats and several PCR primers were designed and tested. We also tested the use of heterologous primers and found that F. virginiana primers amplified products in cultivated strawberry, Fragaria × ananassa Duch. and Fragaria chiloensis. Similarly, microsatellite loci developed from cultivated strawberry also successfully amplified F. virginiana loci. We investigated four microsatellite loci in detail, three developed from F. virginiana and one from cultivated strawberry. A survey of 100 individuals from a population of F. virginiana in Pennsylvania demonstrated high heterozygosities (He or gene diversity ranged from 0.80 to 0.88 per locus) and allelic diversity (12–17 alleles per locus), but individual plants had no more than two alleles per locus. Segregation patterns in parents and progeny of two controlled crosses at these four loci were consistent with disomic Mendelian inheritance. Together these findings suggest that the genome of F. virginiana is "highly diploidized" and at least a subset of microsatellite loci can be treated as codominant, diploid markers. Significant heterozygote deficiencies were found at three of the four loci for hermaphroditic individuals but for only one locus among females in this gynodioecious species.Communicated by J. Dvorak 相似文献
100.
Lee CG Homer RJ Cohn L Link H Jung S Craft JE Graham BS Johnson TR Elias JA 《The Journal of biological chemistry》2002,277(38):35466-35474
To address the complex chronic effector properties of interleukin (IL)-10, we generated transgenic mice in which IL-10 was overexpressed in the lung. In these mice, IL-10 inhibited endotoxin-induced tumor necrosis factor production and neutrophil accumulation. IL-10 also caused mucus metaplasia, B and T cell-rich inflammation, and subepithelial fibrosis and augmented the levels of mRNA encoding Gob-5, mucins, and IL-13. In mice bred to have null mutations of IL-13, IL-4R(alpha), or STAT-6, transgenic IL-10 did not induce mucus metaplasia but did induce inflammation and fibrosis. IL-10 was also a critical mucin regulator of virus-induced mucus metaplasia. Thus, IL-10, although inhibiting lipopolysaccharide-induced inflammation, also causes mucus metaplasia, tissue inflammation, and airway fibrosis. These responses are mediated by multiple mechanisms with mucus metaplasia being dependent on and the inflammation and fibrosis being independent of an IL-13/IL-4R(alpha)/STAT-6 activation pathway. 相似文献