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51.
Genevieve H. L. Roberts Stephanie A. Santorico Richard A. Spritz 《Pigment cell & melanoma research》2020,33(1):8-15
Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome‐wide linkage studies and genome‐wide association studies in European ancestry cases identified over 50 vitiligo susceptibility loci, defining a model of melanocyte‐directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from common and ~1/3 from rare genomic variants; ~20% of vitiligo risk is environmental. Vitiligo genetic risk is polygenic, with greater additive risk in multiplex vitiligo families than simplex cases. Vitiligo age‐of‐onset is bimodal, also involving a major genetic component; a MHC enhancer haplotype confers extreme risk for vitiligo (OR 8.1) and early disease onset, increasing expression of HLA‐DQB1 mRNA and HLA‐DQ protein and thus perhaps facilitating presentation of triggering antigens. Vitiligo triggering also involves a major environmental component; dramatic delay in vitiligo age‐of‐onset, especially from 1973 to 2004, suggests that exposure or response to a key vitiligo environmental trigger diminished during this period. Together, these findings provide deep understanding of vitiligo pathogenesis and genetic architecture, suggesting that vitiligo represents a tractable model for investigating complex disease genetic architecture and predictive aspects of personalized medicine. 相似文献
52.
J Schmitt C Backes N Nourkami-Tutdibi P Leidinger S Deutscher M Beier M Gessler N Graf HP Lenhof A Keller E Meese 《BMC genomics》2012,13(1):379
ABSTRACT: BACKGROUND: Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared themiRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOPprotocol 2001. RESULTS: We did not find a significant difference between miRNA signature of both groups. However both, Wilmstumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. Thesignature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients afterchemotherapy an accuracy of 97.0%, each as compared to healthy controls. CONCLUSION: Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of fourweeks preoperative chemotherapy treatment. 相似文献
53.
用简并寡核苷酸探针筛选对虾白斑综合征病毒DNA多聚酶基因片段 总被引:1,自引:1,他引:1
根据一些病毒的DNA多聚酶氨基酸序列中特有的保守序列VYGDTD设计的简并寡核苷酸,经地高辛标记后与对虾白斑综合征病毒基因库克隆杂交,筛选出一段长度为707 bp的EcoR I基因片段,该片段在一个开放阅读框内.并含DNA多聚酶B家族特有的保守序列YGDTDS.经与基因库比较,其氨基酸序列与藻类DNA病毒科(Phycodnaviridae)的几株藻类病毒的DNA多聚酶片段有部分相似,因此推测该核苷酸片段为对虾白斑综合征病毒DNA多聚酶基因的部分序列. 相似文献
54.
Unterreitmeier S Fuchs A Schäffler T Heym RG Frishman D Langosch D 《Journal of molecular biology》2007,374(3):705-718
Interactions of transmembrane helices play a crucial role in the folding and oligomerisation of integral membrane proteins. In order to uncover novel sequence motifs mediating these interactions, we randomised one face of a transmembrane helix with a set of non-polar or moderately polar amino acids. Those sequences capable of self-interaction upon integration into bacterial inner membranes were selected by means of the ToxR/POSSYCCAT system. A comparison between low/medium-affinity and high-affinity sequences reveals that high-affinity sequences are strongly enriched in phenylalanine residues that are frequently observed at the − 3 position of GxxxG motifs, thus yielding FxxGxxxG motifs. Mutation of Phe or GxxxG in selected sequences significantly reduces self-interaction of the transmembrane domains without affecting their efficiency of membrane integration. Conversely, grafting FxxGxxxG onto unrelated transmembrane domains strongly enhances their interaction. Further, we find that FxxGxxxG is significantly over-represented in transmembrane domains of bitopic membrane proteins. The same motif contributes to self-interaction of the vesicular stomatitis virus G protein transmembrane domain. We conclude that Phe stabilises membrane-spanning GxxxG motifs. This is one example of how the role of certain side-chains in helix-helix interfaces is modulated by sequence context. 相似文献
55.
Bulwin GC Wälter S Schlawinsky M Heinemann T Schulze A Höhne W Krause G Kalka-Moll W Fraser P Volk HD Löhler J Milford EL Utku N 《PloS one》2008,3(2):e1576
Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-zeta chain & ZAP70, and inhibition of IFN-gamma and FasL expression. HLA-DRalpha2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRalpha2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway. 相似文献
56.
Predictions of stream nutrient and sediment yield changes following restoration of forested riparian buffers 总被引:6,自引:1,他引:6
Stephanie M. Parkyn Robert J. Davies-Colley A. Bryce Cooper Morag J. Stroud 《Ecological Engineering》2005,24(5):551-558
Riparian tree planting is widely recognised as a means to improve water quality and stream habitat. However, shading of riparian pasture grasses can lead to channel widening, and riparian shade may limit the growth of macrophytes and algae that assimilate dissolved nutrients from the water column. We investigated concerns that riparian management could lead to increased yields of nutrients and sediments through a conceptual modelling exercise. A simple model of the trade-off between interception of nutrients in runoff by forest buffers versus reduction of in-stream uptake due to shade, predicted that a buffer strip alongside a small headwater stream would reduce nutrient export, while a buffer strip instigated as an isolated patch alongside a larger stream (c. >2.5 km2 upstream catchment size) would increase nutrient export, as the relative amount of nutrients trapped by the buffer decreases as the nutrient load present in the stream water increases. However, in these larger streams with width exceeding approximately 6 m, sufficient light may reach the streambed for plant and algal growth, which in turn would promote instream nutrient processing. At the peak of streambank erosion after planting, predicted total sediment yield (hillslope plus bank sources) was appreciably higher than the hillslope pasture yield, but sediment yield stabilised c. 35–40 years after planting. When planting was extended over 40 years in the model, the sediment yield never exceeded that in pasture before planting. This conceptual modelling exercise shows that riparian tree planting programmes should commence in the headwaters and progress downstream to avoid nutrient yield increases. Significant sediment yield from bank stored sediment of small streams can be expected until the channel reaches the more stable, original forested width, but progressive planting may decrease the peak loads of sediment. 相似文献
57.
58.
The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation 总被引:5,自引:0,他引:5
Wang G Chuang L Zhang X Colton S Dombkowski A Reiners J Diakiw A Xu XS 《Nucleic acids research》2004,32(7):2231-2240
XPC is an important DNA damage recognition protein involved in DNA nucleotide excision repair. We have studied the role of the XPC protein in cisplatin treatment-mediated cell cycle regulation. Through the comparison of microarray data obtained from human normal fibroblasts and two individual XPC-defective cell lines, 486 genes were identified as XPC-responsive genes in the cisplatin treatment (with a minimal 1.5-fold change) and 297 of these genes were further mapped to biological pathways and gene ontologies. The cell cycle and cell proliferation-related genes were the most affected genes by the XPC defect in the cisplatin treatment. Many other cellular function genes were also affected by the XPC defect in the treatment. Western blot hybridization results revealed that the XPC defect reduced the p53 responses to the cisplatin treatment. The ability to activate caspase-3 was also attenuated in the XPC cells with the treatment. These results suggest that the XPC protein plays a critical role in initiating the cisplatin DNA damaging treatment-mediated signal transduction process, resulting in activation of the p53 pathway and cell cycle arrest that allow DNA repair and apoptosis to take place. These results reveal an important role of the XPC protein in the cancer prevention. 相似文献
59.
60.
Seav‐Ly Tran Lucile Billoud Steven B. Lewis Alan D. Phillips Stephanie Schüller 《Cellular microbiology》2014,16(8):1255-1266
Haemolytic uraemic syndrome caused by Shiga toxin‐producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx‐related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx‐related events and enhance Stx absorption during STEC infection. 相似文献