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排序方式: 共有91条查询结果,搜索用时 15 毫秒
81.
Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia 总被引:24,自引:0,他引:24
Hahn CG Wang HY Cho DS Talbot K Gur RE Berrettini WH Bakshi K Kamins J Borgmann-Winter KE Siegel SJ Gallop RJ Arnold SE 《Nature medicine》2006,12(7):824-828
Recent molecular genetics studies implicate neuregulin 1 (NRG1) and its receptor erbB in the pathophysiology of schizophrenia. Among NRG1 receptors, erbB4 is of particular interest because of its crucial roles in neurodevelopment and in the modulation of N-methyl-D-aspartate (NMDA) receptor signaling. Here, using a new postmortem tissue-stimulation approach, we show a marked increase in NRG1-induced activation of erbB4 in the prefrontal cortex in schizophrenia. Levels of NRG1 and erbB4, however, did not differ between schizophrenia and control groups. To evaluate possible causes for this hyperactivation of erbB4 signaling, we examined the association of erbB4 with PSD-95 (postsynaptic density protein of 95 kDa), as this association has been shown to facilitate activation of erbB4. Schizophrenia subjects showed substantial increases in erbB4-PSD-95 interactions. We found that NRG1 stimulation suppresses NMDA receptor activation in the human prefrontal cortex, as previously reported in the rodent cortex. NRG1-induced suppression of NMDA receptor activation was more pronounced in schizophrenia subjects than in controls, consistent with enhanced NRG1-erbB4 signaling seen in this illness. Therefore, these findings suggest that enhanced NRG1 signaling may contribute to NMDA hypofunction in schizophrenia. 相似文献
82.
Nuno A Fonseca Cristina P Vieira Peter WH Holland Jorge Vieira 《BMC evolutionary biology》2008,8(1):200
Background
Although homeobox genes have been the subject of many studies, little is known about the main amino acid changes that occurred early in the evolution of genes belonging to different classes. 相似文献83.
Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q 总被引:4,自引:1,他引:3 下载免费PDF全文
McQueen MB Devlin B Faraone SV Nimgaonkar VL Sklar P Smoller JW Abou Jamra R Albus M Bacanu SA Baron M Barrett TB Berrettini W Blacker D Byerley W Cichon S Coryell W Craddock N Daly MJ Depaulo JR Edenberg HJ Foroud T Gill M Gilliam TC Hamshere M Jones I Jones L Juo SH Kelsoe JR Lambert D Lange C Lerer B Liu J Maier W Mackinnon JD McInnis MG McMahon FJ Murphy DL Nothen MM Nurnberger JI Pato CN Pato MT Potash JB Propping P Pulver AE Rice JP Rietschel M Scheftner W Schumacher J Segurado R 《American journal of human genetics》2005,77(4):582-595
Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches. 相似文献
84.
The consumption of fermented foods contaminated with aflatoxin B1 is linked to aflatoxicosis. Aflatoxicosis is a serious problem in developing countries with environmental conditions appropriate for the biosynthesis of AFB1 byAspergillus flavus andAspergillus parasiticus. In Africa, especially in Ghana and Nigeria, there is a very high risk of liver cancer which is caused by the consumption of AFB1-intoxicated, traditionally fermented maize and sorghum products. It is suggested that one way to diminish this health risk might be the reduction of the AFB1 concentration in foods by bacteria. Especially bacteria used for food fermentation processes are of great importance, with a special emphasis on lactic acid bacteria which are involved in traditionally fermented African foods based on maize and sorghum.Most publications dealing with aflatoxin degradation by microorganisms describe a phosphate buffer test system for the performance of degradation experiments. In contrast to that, a test system based on physiological active bacterial and yeast cells has been developed, to assess food fermentation organisms for their ability to reduce the AFB1 concentration in vitro. The aflatoxin B1 concentration in test samples was quatitatively determined by HPLC.The assessment of lactic acid bacteria originating from different German and other European culture collections only showed a very slight reduction of the AFB1 concentration from 3% to 12%. Screening experiments in which other bacterial genera and lactic acid bacteria, isolated from different African foods have been assessed, in most cases showed the same results. However, some bacterial strains, e.g. strains of the genusBacillus derived from European culture collections and strains of the genusLactobacillus isolated from African foods, caused a release of AFB1 which was chemically bound before to components of the test medium and which therefore could not be extracted with chloroform.A process quite similar to that may happen during food fermentations. Different experiments showed that e.g. cellulose can bind AFB1 very effectively. Cellulose and different other food components are well known to absorb AFB1. During fermentation the cellulose and other AFB1-absorbing components may be degraded and the AFB1 will be released again.The only bacterial strain known as yet which is able to reduce the AFB1 concentration in vitro and in different food comodities isNocardia corynebacteroides (formerFlavobacterium aurantiacum). Nevertheless the mechanism of this AFB1 reduction is actually not well understood, it still has to be investigated. In the meantime several other bacterial strains, presumably from the taxonomic group of theActinomycetes could be proved to be effective reducers of the AFB1 concentration in our in vitro test system. Because as yet no food relevant microorganism could be found, which is able to degrade AFB1, these new strains in general offer the possibility for a genetic modification of food relevant microorganisms. This seems to be the way to come to starter cultures which are able to degrade AFB1 during food fermentations. 相似文献
85.
The influence of sex of broilers and dietary phosphorus (P) level on energy utilization and apparent ileal digestibility of N, P and phytate-P were investigated. The AMEN was determined using 3- and 6-week old broilers, while the apparent ileal digestibility were determined only with 6-week old birds. Sex of broilers had no effect on the AMEN values determined during week 3. During week 6, the AMEN values for male broilers were higher (P?0.01) than those for the females. An interaction (P?0.05) between sex and dietary P level was also observed. AMEN values determined with male broilers were lower in the adequate-P diet compared to those in the low-P diet, whereas no effect of P level was observed in females. Female broilers tended (P?0.10) to have a higher ileal N digestibility than the males, but a significant (P?0.01) sex ×?P level interaction was observed. Males receiving the adequate-P diet had a lower N digestibility than those receiving the low-P diet, whereas the opposite was true in the females. Ileal phytate P degradation in males was higher than in females (0.282 vs. 0.234), but the differences were not significant. Increasing dietary P level increased ileal P digestibility in both the males and females, but the improvements were greater in the females, as indicated by a significant sex × P level interaction. 相似文献
86.
Bjorn?WH?van Heumen Hennie?MJ?Roelofs René?HM?te Morsche Fokko?M?Nagengast Wilbert?HM?PetersEmail author 《Orphanet journal of rare diseases》2013,8(1):181
Background
Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.Methods
Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.Results
mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.Conclusions
Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.Trial registration
http://ClinicalTrials.gov number NCT0080874387.
The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias 总被引:31,自引:14,他引:31
Genes sequences from Escherichia coli, Salmonella typhimurium, and other
members of the Enterobacteriaceae show a negative correlation between the
degree of synonymous-codon usage bias and the rate of nucleotide
substitution at synonymous sites. In particular, very highly expressed
genes have very biased codon usage and accumulate synonymous substitutions
very slowly. In contrast, there is little correlation between the degree of
codon bias and the rate of protein evolution. It is concluded that both the
rate of synonymous substitution and the degree of codon usage bias largely
reflect the intensity of selection at the translational level. Because of
the high variability among genes in rates of synonymous substitution,
separate molecular clocks of synonymous substitution might be required for
different genes.
相似文献
88.
89.
90.
Retention of cryptic genes in microbial populations 总被引:5,自引:0,他引:5
Cryptic genes are silenced genes that can still be reactivated by mutation.
Since they can make no positive contribution to the fitness of their
carriers, it is not clear why many cryptic genes in microbial populations
have not degenerated into useless DNA sequences. Hall et al. (1983) have
suggested that cryptic genes have persisted because of occasional strong
environmental selection for reactivated genes. The present mathematical
study supports their suggestion. It shows that a cryptic gene can be
retained without having any selective advantage over a useless DNA
sequence, if selection for the reactivated gene occasionally occurs for a
substantially long time.
相似文献