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161.
Xin Li Liming Liang Mingfeng Zhang Fengju Song Hongmei Nan Li-E Wang Qingyi Wei Jeffrey E. Lee Christopher I. Amos Abrar A. Qureshi Jiali Han 《Human genetics》2013,132(7):793-801
Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles = 0.12, P value = 4 × 10?5). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R 2 quality metric >0.8 using the 1,000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity. 相似文献
162.
Tricho–rhino–phalangeal syndrome (TRPS) is a rare autosomal dominant disorder. Deletion or mutation of the TRPS1 gene leads to the tricho–rhino–phalangeal syndromes type I or type III. In this article, we describe a Chinese patient affected with type I TRPS and showing prominent pilar, rhinal and phalangeal abnormalities. Mutational screening and sequence analysis of TRPS1 gene revealed a previously unidentified four-base-pair deletion of nucleotides 1783–1786 (c.1783_1786delACTT). The mutation causes a frame shift after codon 593, introducing a premature stop codon after 637 residues in the gene sequence. This deletion is an unquestionable loss-of-function mutation, deleting all the functionally important parts of the protein. Our novel discovery indicates that sparse hair and metacarpal defects of tricho–rhino–phalangeal syndromes in this patient are due to this TRPS1 mutation. And this data further supports the critical role of TRPS1 gene in hair and partial skeleton morphogenesis. 相似文献
163.
164.
165.
Nan Liang Lili Jia Yang Liu Bing Liang Dejuan Kong Mengmeng Yan Shumei Ma Xiaodong Liu 《Cellular signalling》2013,25(12):2530-2539
BackgroundATM plays an important role in response to DNA damage, while the roles of ATM in radiation-induced autophagy are still unclear in cervical cancer cells.MethodsHuman cervical cancer cells, Hela, were used, and cell models with ATM?/? and MAPK14?/? were established by gene engineering. Western blot was implemented to detect protein expression. MDC staining and GFP-LC3 relocalization were used to detect autophagy. CCK-8 was used to detect cell viability. Radiosensitivity was analyzed by colony formation assays. Co-immunoprecipitation was used to detect the interaction between different proteins, and apoptosis was detected by flow cytometry.ResultsAfter radiation autophagy was induced, illustrated by the increase of MAPLC3-II/MAPLC3-I ratio and decrease of p62, and phosphorylation of ATM simultaneously increased. ATM?/? cells displayed hypersensitivity but had no influence on IR-induced apoptosis. Then inhibitor of ATM, KU55933, ATM and MAPK14 silencing were used, and autophagy was induced by IR more than 200% in control, and only by 35.72%, 53.18% and 24.76% in KU55933-treated cells, ATM?/? and MAPK14?/? cells, respectively. KU55933 inhibited IR-induced autophagy by activating mTOR pathways. ATM silencing decreased the expression of MAPK14 and mTOR signals significantly. Beclin's bond to PI3KIII and their interaction increased after IR, while in ATM?/? and MAPK14?/? cells this interaction decreased after IR. Both ATM and MAPK14 interacted with Beclin, while ATM?/? and MAPK14?/? cells showed no interaction.ConclusionsATM could promote IR-induced autophagy via the MAPK14 pathway, the mTOR pathway, and Beclin/PI3KIII complexes, which contributed to the effect of ATM on radiosensitivity. 相似文献
166.
167.
The microbial reduction process of goethite by Shewanella decolorationis S12 was evaluated. The results showed the electron shuttle, anthraquinone-2-sulfonate (AQS), could enhance the microbial reduction. The thermodynamic and kinetic characteristics of goethite reduction by microorganisms were influenced by AQS, concentrations of iron oxide, and electron donor. Transformation between oxidized and reduced species of the electron shuttle during the microbial reduction could be newly noticed. Two interactive steps, biotic and abiotic, were involved in the microbial reduction of Fe (III) oxide mediated by electron shuttle. 相似文献
168.
Xiaofei Liu Nan Zuo Huanan Guan Chunran Han Shi Wen Xu 《Biological trace element research》2013,154(2):202-209
Exposure to Manganese (Mn) is a common phenomenon due to its environmental pervasiveness. To investigate the Mn-induced toxicity on cerebral trace element levels and crucial nitric oxide parameters on brain of birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet containing 600, 900, 1,800 mg kg?1. After being treated with Mn for 30, 60, and 90 days, the following were determined: the changes in contents of copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), selenium (Se) in brain; inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity in brain; and histopathology and ultrastructure changes of cerebral cortex. The results showed that Mn was accumulated in brain and the content of Cu and Fe increased. However, the levels of Zn and Se decreased and the Ca content presented no obvious regularity. Exposure to Mn significantly elevated the content of NO and the expression of iNOS mRNA. Activity of total NO synthase (T NOS) and iNOS appeared with an increased tendency. These findings suggested that Mn exposure resulted in the imbalance of cerebral trace elements and influenced iNOS in the molecular level, which are possible underlying nervous system injury mechanisms induced by Mn exposure. 相似文献
169.
Ruodan Nan Stuart Tetchner Elizabeth Rodriguez Po-Jung Pao Jayesh Gor Imre Lengyel Stephen J. Perkins 《The Journal of biological chemistry》2013,288(26):19197-19210
The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular
degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of
complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3.
During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor
H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical
ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100
μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble
oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with
zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions
showed that putative weak zinc binding sites with different capacities exist in all five proteins,
in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In
contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much
reduced at 60 μm zinc and even more so at >100 μm zinc. The
removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc.
Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment
epithelial deposits in the retina as well as reducing the progression to advanced age-related
macular degeneration in higher risk patients. 相似文献
170.
Jingjing Ben Yan Zhang Rongmei Zhou Haiyang Zhang Xudong Zhu Xiaoyu Li Hanwen Zhang Nan Li Xiaodan Zhou Hui Bai Qing Yang Donghai Li Yong Xu Qi Chen 《The Journal of biological chemistry》2013,288(27):20076-20084
Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis. 相似文献