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排序方式: 共有133条查询结果,搜索用时 31 毫秒
71.
Stoeckius M Erat A Fujikawa T Hiromura M Koulova A Otterbein L Bianchi C Tobiasch E Dagon Y Sellke FW Usheva A 《The Journal of biological chemistry》2012,287(19):15418-15426
72.
Martínez-Solano I Peralta-García A Jockusch EL Wake DB Vázquez-Domínguez E Parra-Olea G 《Molecular phylogenetics and evolution》2012,63(1):131-149
Inferences about species boundaries and evolutionary history are often complicated by discordance between datasets. In recent times, considerable effort has been devoted to understanding the causes of discordance between the patterns of genetic variation and structure shown by different unlinked molecular markers. The genus Batrachoseps (Caudata, Plethodontidae), the most diverse group of salamanders in western North America, is characterized by limited morphological variation and discordance between molecular datasets, making it a challenging group for taxonomists but also a good model to test newly developed analytical methods to sort out possible sources of discordance. In this study, we present a comprehensive assessment of the evolutionary history of B. major, one of the most widespread species in the genus, based on extensive sampling and phylogenetic and coalescent analyses of data from mitochondrial and nuclear markers. We found non-monophyly of mtDNA in B. major, with two lineages (northern and southern) that are more closely related to other species in the genus than to each other, but this division was not apparent in nuclear DNA. Despite non-monophyly in gene trees, species tree analyses recovered a sister group relationship between the two lineages of B. major, and coalescent simulations suggested that there is no need to invoke gene flow to account for the discordance across gene trees. The possibility that these two lineages represent sister, cryptic taxa, is discussed in the context of Bayesian methods of species/lineage delineation. Contrary to prior expectations, B. major has experienced extensive diversification on the Baja California Peninsula, where four endemic lineages have persisted for at least 4 million years. 相似文献
73.
Synthesis and post-translational processing of retinal proenkephalin in response to the light or darkness were studied in newly hatched chickens using chromatography, enzymatic digestion (trypsin-carboxypeptidase B) and radioimmunoassay. We found that the concentration of free [Met5]-enkephalin in crude retinal extracts increased with the time in the light and decreased in the dark. This effect was directly dependent on illumination, rather than the consequence of an endogenous circadian rhythm. In contrast, the total amount of cryptic [Met5]-enkephalin (in larger enkephalin-containing polypeptides) remained constant in all stages of the light/dark cycle. We also showed that the relative amounts of cryptic [Met5]-enkephalin stored at different molecular weights remained constant, and that the concentrations of three identified proenkephalin-derived peptides, [Met5]-enkephalin, [Leu5]-enkephalin and [Met5]-enkephalin-Arg6-Phe7, were higher in the light-adapted than in the dark-adapted retina; but the relative amounts (ratios) of the three proenkephalin-derived peptides stored in the light and in the dark were equal. These data are consistent with the hypothesis that synthesis and processing of proenkephalin proceed at a constant rate and with similar pattern independent of illumination or adaptation, whereas the processed enkephalins are released preferentially in the darkness and accumulated in the light. 相似文献
74.
75.
John Blazeck Jarrett Miller Anny Pan Jon Gengler Clinton Holden Mariam Jamoussi Hal S. Alper 《Applied microbiology and biotechnology》2014,98(19):8155-8164
Renewable alternatives for petroleum-derived chemicals are achievable through biosynthetic production. Here, we utilize Saccharomyces cerevisiae to enable the synthesis of itaconic acid, a molecule with diverse applications as a petrochemical replacement. We first optimize pathway expression within S. cerevisiae through the use of a hybrid promoter. Next, we utilize sequential, in silico computational genome-scanning to identify beneficial genetic perturbations that are metabolically distant from the itaconic acid synthesis pathway. In this manner, we successfully identify three non-obvious genetic targets (?ade3 ?bna2 ?tes1) that successively improve itaconic acid titer. We establish that focused manipulations of upstream pathway enzymes (localized refactoring) and enzyme re-localization to both mitochondria and cytosol fail to improve itaconic acid titers. Finally, we establish a higher cell density fermentation that ultimately achieves itaconic acid titer of 168 mg/L, a sevenfold improvement over initial conditions. This work represents an attempt to increase itaconic acid production in yeast and demonstrates the successful utilization of computationally guided genetic manipulation to increase metabolic capacity. 相似文献
76.
Mark O. Goodarzi Carl D. Langefeld Anny H. Xiang Yii‐Der I. Chen Xiuqing Guo Anthony J. G. Hanley Leslie J. Raffel Fouad Kandeel Jerry L. Nadler Thomas A. Buchanan Jill M. Norris Tasha E. Fingerlin Carlos Lorenzo Marian J. Rewers Steven M. Haffner Donald W. Bowden Stephen S. Rich Richard N. Bergman Jerome I. Rotter Richard M. Watanabe Lynne E. Wagenknecht 《Obesity (Silver Spring, Md.)》2014,22(4):1157-1164
77.
78.
Zimon A Erat A Von Wald T Bissell B Koulova A Choi CH Bachvarov D Reindollar RH Usheva A 《Nucleic acids research》2006,34(11):3279-3287
Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene–protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function. 相似文献
79.
Gelev V Aktas H Marintchev A Ito T Frueh D Hemond M Rovnyak D Debus M Hyberts S Usheva A Halperin J Wagner G 《Journal of molecular biology》2006,364(3):352-363
The dsRNA-dependent protein kinase (PKR) is a key mediator of the anti-viral and anti-proliferative effects of interferon. Unphosphorylated PKR is characterized by inhibitory interactions between the kinase and RNA binding domains (RBDs), but the structural details of the latent state and its unraveling during activation are not well understood. To study PKR regulation by NMR we assigned a large portion of the backbone resonances of the catalytically inactive K296R kinase domain, and performed (15)N-heteronuclear single quantum coherence (HSQC) titrations of this kinase domain with the RBDs. Chemical shift perturbations in the kinase indicate that RBD2 binds to the substrate eIF2alpha docking site in the kinase C-lobe. Consistent with these results, a mutation in the eIF2alpha docking site, F495A, displays weaker interactions with the RBD. The full-length RBD1+2 binds more strongly to the kinase domain than RBD2 alone. The observed chemical shift changes extend from the eIF2alpha binding site into the kinase N-lobe and inside the active site, consistent with weak interactions between the N-terminal part of the RBD and the kinase. 相似文献
80.
Norseen J Hosooka T Hammarstedt A Yore MM Kant S Aryal P Kiernan UA Phillips DA Maruyama H Kraus BJ Usheva A Davis RJ Smith U Kahn BB 《Molecular and cellular biology》2012,32(10):2010-2019
Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4-/- macrophages. Because RBP4 is a retinol-binding protein, we investigated whether these effects are retinol dependent. Unexpectedly, retinol-free RBP4 (apo-RBP4) is as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory cytokines in macrophages. Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4. 相似文献