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71.

Objective

First, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk.

Methods

We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.2±2.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011.

Results

Compared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10–0.97) and among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33–0.98) or >60 g alcohol/d (HR = 0.30; 95% CI: 0.12–0.78). Stroke risk was not significantly related to alcohol consumption >6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slow-coding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98–1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90–1.27; p for heterogeneity: 0.098)].

Conclusion

The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation.  相似文献   
72.
Ohne Zusammenfassung  相似文献   
73.
Photosynthesis Research - Light-harvesting complex II (LHCII) is the major antenna complex in higher plants and green algae. It has been suggested that a major part of the excited state energy...  相似文献   
74.
The Santee-Cooper ranaviruses doctor fish virus (DFV), guppy virus 6 (GV6), and largemouth bass virus (LMBV) are members of the genus Ranavirus within the family Iridoviridae. The major capsid protein (MCP) is a main structural protein of iridoviruses and supports the differentiation and classification of ranaviruses. Presently the complete sequence of the MCP gene is known for most ranaviruses with the exception of the Santee-Cooper ranaviruses. In the present study, the complete nucleotide sequence of the MCP gene of DFV, GV6, and LMBV was determined. DFV and GV6 are identical within the MCP gene sequence. The identity compared to the corresponding sequence in LMBV amounts to 99.21%. The MCP gene of DFV, GV6, and LMBV exhibits only approximately 78% identity compared to the respective gene of other ranaviruses. Based on the sequence data obtained in the present study, a Rana MCP polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) analysis were developed to identify and differentiate ranaviruses, including DFV, GV6, and LMBV.  相似文献   
75.
Insulin-degrading enzyme (IDE) is a Zn(2+) metalloprotease with a characteristic inverted catalytic motif. IDE is ubiquitously expressed and degrades peptide substrates including insulin, endorphin, and the amyloid-β peptide. Although IDE is mainly expressed in the cytosol, it can also be found on the cell surface and in secreted form in extracellular fluids. As IDE lacks a characteristic signal sequence that targets the protein to the classical secretory pathway, release of the enzyme involves non-conventional mechanisms. However, functional domains of IDE involved in its secretion remain elusive. By bioinformatical, biochemical, and cell biological methods, we identified a novel amino acid motif ((853)EKPPHY(858)) close to the C terminus of IDE and characterized its function in the non-conventional secretion of the protein. Because of its close homology to an amino acid sequence found in bacterial proteins belonging to the SlyX family, we propose to call it the SlyX motif. Mutagenesis revealed that deletion of this motif strongly decreased the release of IDE, whereas deletion of a potential microbody-targeting signal at the extreme C terminus had little effect on secretion. The combined data indicate that the non-conventional secretion of IDE is regulated by the newly identified SlyX motif.  相似文献   
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Smaug, a protein repressing translation and inducing mRNA decay, directly controls an unexpectedly large number of maternal mRNAs driving early Drosophila development.See related research, http://genomebiology.com/2014/15/1/R4Regulation of translation and mRNA stability is a key aspect of early metazoan development. One of the best studied factors involved in these processes is the Drosophila protein Smaug. In this issue of Genome Biology, Chen et al. [1] report that a large number of maternal mRNAs in the fly embryo are probably regulated directly by Smaug.  相似文献   
78.
The physiological function of the cellular prion protein (PrPc) is unclear. PrPc associates with lipid rafts, highly glycolipid-rich membrane domains containing a large variety of signaling molecules, e.g., sphingolipids (SL). In this study, we investigated possible connections between PrPc and sphingolipid-associated signaling pathways. Using PrPc-wt and PrPc-k.o. hippocampal cell lines and mouse brains we showed higher activity of neutral and acid sphingomyelinase (SMase) in PrPc-k.o.-groups, while ceramide and sphingomyelin-levels were unchanged. Furthermore, despite lower basal expression levels of sphingosine kinase (SphK) in PrPc-k.o.-groups, the levels of its metabolite sphingosine-1-phosphate were increased, whereas S1P3-receptor expression was higher in PrPc-wt-groups again. In addition, we detected enhanced activity of phospholipase D1, an enzyme that seems to be suitable to act as a connector between the S1P3 receptor and continuative signaling. Finally, evidence for an impact on downstream signaling cascades, especially activation of the PI3K/Akt pathway, was found. In summary, our data suggest that PrPc is involved in sphingolipid-associated signaling, modulating pathways that exert anti-apoptotic functions, hence indicating that PrPc plays a role in neuroprotection.  相似文献   
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