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- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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- Glad, Camilla A M, 1981, et al.
(författare)
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Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:5, s. 1459-1470
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Tidskriftsartikel (refereegranskat)abstract
- GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking.The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding.Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding.GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P < 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P < 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity.The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.
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- Heinrichs, Jannica, 1982-, et al.
(författare)
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Wear mechanisms of WC-Co cemented carbide tools and PVD coated tools used for shearing Cu-alloy wire in zipper production
- 2019
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 420, s. 96-107
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Tidskriftsartikel (refereegranskat)abstract
- To form the individual elements, that together form a zipper, a pre-formed Cu-alloy wire is sheared using cemented carbide tools. The wear caused by the relatively soft copper alloy on the much harder tool is generally quite slow. However, millions of elements are to be sheared so eventually the wear becomes unacceptable and the tool needs to be exchanged. To improve product quality, as well as minimize down time and material consumption, the tool life needs to be prolonged. To achieve this the wear process needs to be better understood. Uncoated tools used for an increasing number of shearing events have been studied in detail using high resolution SEM and EDS, to map the propagating wear and get an insight into the wear mechanisms. Transfer of material from the Cu-alloy to the tool occurs and the wear is highly concentrated to specific areas. This wear occurs on a very fine scale, limited to within individual WC grains at each event. Tools coated with PVD CrC and PVD CrN have been studied for comparison with the uncoated cemented carbide. Both coatings successfully protect the cemented carbide tool from wear, however occasional flaking occurs and then the cemented carbide becomes exposed and subsequently worn. The differences in performance and wear mechanisms between the uncoated and coated tools are discussed, with focus on the capability of the coatings to prolong the tool life.
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