排序方式: 共有259条查询结果,搜索用时 140 毫秒
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Marzi C Albrecht E Hysi PG Lagou V Waldenberger M Tönjes A Prokopenko I Heim K Blackburn H Ried JS Kleber ME Mangino M Thorand B Peters A Hammond CJ Grallert H Boehm BO Kovacs P Geistlinger L Prokisch H Winkelmann BR Spector TD Wichmann HE Stumvoll M Soranzo N März W Koenig W Illig T Gieger C 《PLoS genetics》2010,6(11):e1001213
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Low levels of genetic divergence across geographically and linguistically diverse populations from India
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Rosenberg NA Mahajan S Gonzalez-Quevedo C Blum MG Nino-Rosales L Ninis V Das P Hegde M Molinari L Zapata G Weber JL Belmont JW Patel PI 《PLoS genetics》2006,2(12):e215
Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States–sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population. 相似文献
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DKWSLLL,a Versatile DXXXLL‐Type Signal with Distinct Roles in the Cu+‐Regulated Trafficking of ATP7B
Vasiliki Lalioti Sonia Hernandez‐Tiedra Ignacio V. Sandoval 《Traffic (Copenhagen, Denmark)》2014,15(8):839-860
In the liver, the P‐type ATPase and membrane pump ATP7B plays a crucial role in Cu+ donation to cuproenzymes and in the elimination of excess Cu+. ATP7B is endowed with a COOH‐cytoplasmic (DE)XXXLL‐type traffic signal. We find that accessory (Lys ?3, Trp ?2, Ser ?1 and Leu +2) and canonical (D ?4, Leu 0 and Leu +1) residues confer the DKWSLLL signal with the versatility required for the Cu+‐regulated cycling of ATP7B between the trans‐Golgi network (TGN) and the plasma membrane (PM). The separate mutation of these residues caused a disruption of the signal, resulting in different ATP7B distribution phenotypes. These phenotypes indicate the key roles of specific residues at separate steps of ATP7B trafficking, including sorting at the TGN, transport from the TGN to the PM and its endocytosis, and recycling to the TGN and PM. The distinct roles of ATP7B in the TGN and PM and the variety of phenotypes caused by the mutation of the canonical and accessory residues of the DKWSLLL signal can explain the separate or joined presentation of Wilson's cuprotoxicosis and the dysfunction of the cuproenzymes that accept Cu+ at the TGN. 相似文献
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Efstratios K. Kosmidis Vasiliki Moschou Georgios Ziogas Ioannis Boukovinas Maria Albani Nikolaos A. Laskaris 《PloS one》2014,9(11)
The EGF-induced MAP kinase cascade is one of the most important and best characterized networks in intracellular signalling. It has a vital role in the development and maturation of living organisms. However, when deregulated, it is involved in the onset of a number of diseases. Based on a computational model describing a “surface” and an “internalized” parallel route, we use systems biology techniques to characterize aspects of the network’s functional organization. We examine the re-organization of protein groups from low to high external stimulation, define functional groups of proteins within the network, determine the parameter best encoding for input intensity and predict the effect of protein removal to the system’s output response. Extensive functional re-organization of proteins is observed in the lower end of stimulus concentrations. As we move to higher concentrations the variability is less pronounced. 6 functional groups have emerged from a consensus clustering approach, reflecting different dynamical aspects of the network. Mutual information investigation revealed that the maximum activation rate of the two output proteins best encodes for stimulus intensity. Removal of each protein of the network resulted in a range of graded effects, from complete silencing to intense activation. Our results provide a new “vista” of the EGF-induced MAP kinase cascade, from the perspective of complex self-organizing systems. Functional grouping of the proteins reveals an organizational scheme contrasting the current understanding of modular topology. The six identified groups may provide the means to experimentally follow the dynamics of this complex network. Also, the vulnerability analysis approach may be used for the development of novel therapeutic targets in the context of personalized medicine. 相似文献
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Vasiliki Gkretsi Vassilis Papanikolaou Stephanie Dubos Ioanna Papathanasiou Nikolina Giotopoulou Vaia Valiakou Chuanyue Wu Konstantinos N. Malizos Aspasia Tsezou 《Biochemical and biophysical research communications》2013,430(2):494-499
Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell–ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and β-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with β-catenin. Thus, the present study emphasizes for the first time to our knowledge the role of Migfilin in OA and highlights the importance of cell–ECM adhesion proteins in OA pathogenesis. 相似文献
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Vasiliki Mavroeidi Ioannis Petrakis Kostas Stylianou Theodora Katsarou Konstantinos Giannakakis Kostas Perakis Eleftheria Vardaki Spyridon Stratigis Emmanuel Ganotakis Stathis Papavasiliou Eugenios Daphnis 《The journal of histochemistry and cytochemistry》2013,61(6):433-443
The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan. 相似文献
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