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- Allagnat, F., et al.
(författare)
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C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in beta-cells
- 2012
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Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 19:11, s. 1836-1846
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Tidskriftsartikel (refereegranskat)abstract
- Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic beta-cells. Pro-inflammatory cytokines are early mediators of beta-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in beta-cells, but the role for CHOP overexpression in cytokine-induced beta-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-kappa B (NF-kappa B) is a crucial transcription factor regulating beta-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-kappa B activity and expression of key NF-kappa B target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased I kappa B degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting beta-cell death: (1) CHOP directly contributes to cytokine-induced beta-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-kappa B activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis. Cell Death and Differentiation (2012) 19, 1836-1846; doi:10.1038/cdd.2012.67; published online 1 June 2012
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- Fukaya, Eri, et al.
(författare)
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Clinical and Genetic Determinants of Varicose Veins Prospective, Community-Based Study of approximate to 500 000 Individuals
- 2018
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 138:25, s. 2869-2880
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS: We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS: Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% Cl, 1.51-2.01; P<0.0001). A genomewide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/ limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse -variance weighted: odds ratio, 1.26; P=2.07x10(-16)). CONCLUSIONS: Using data from nearly a half -million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
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- Hoban, Sean, et al.
(författare)
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Monitoring status and trends in genetic diversity for the Convention on Biological Diversity : An ongoing assessment of genetic indicators in nine countries
- 2023
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Ingår i: Conservation Letters. - 1755-263X. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Recent scientific evidence shows that genetic diversity must be maintained, managed, and monitored to protect biodiversity and nature's contributions to people. Three genetic diversity indicators, two of which do not require DNA-based assessment, have been proposed for reporting to the Convention on Biological Diversity and other conservation and policy initiatives. These indicators allow an approximation of the status and trends of genetic diversity to inform policy, using existing demographic and geographic information. Application of these indicators has been initiated and here we describe ongoing efforts in calculating these indicators with examples. We specifically describe a project underway to apply these indicators in nine countries, provide example calculations, address concerns of policy makers and implementation challenges, and describe a roadmap for further development and deployment, incorporating feedback from the broader community. We also present guidance documents and data collection tools for calculating indicators. We demonstrate that Parties can successfully and cost-effectively report these genetic diversity indicators with existing biodiversity observation data, and, in doing so, better conserve the Earth's biodiversity.
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- Yamamoto, Kohei, et al.
(författare)
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Ultrafast demagnetization of Pt magnetic moment in L1(0)-FePt probed by magnetic circular dichroism at a hard x-ray free electron laser
- 2019
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Ingår i: New Journal of Physics. - : IOP PUBLISHING LTD. - 1367-2630. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- Unraveling the origin of ultrafast demagnetization in multisublattice ferromagnetic materials requires femtosecond x-ray techniques to trace the magnetic moment dynamics on individual elements, but this could not yet be achieved in the hard x-ray regime. We demonstrate here the first ultrafast demagnetization dynamics in the ferromagnetic heavy 5d-transition metal Pt using circularly-polarized hard x-rays at an x-ray free electron laser (XFEL). The decay time of laser-induced demagnetization of L1(0)-FePt is determined to be tau(Pt) = 0.61 +/- 0.04 ps using time-resolved x-ray magnetic circular dichroism at the Pt L-3 edge, whereas magneto-optical Kerr measurements indicate the decay time for the total magnetization as tau(total) < 0.1 ps. A transient magnetic state with a photomodulated ratio of the 3d and 5d magnetic moments is demonstrated for pump-probe delays larger than 1 ps. We explain this distinct photo-modulated transient magnetic state by the induced-moment behavior of the Pt atom and the x-ray probing depth. Our findings pave the way for the future use of XFELs to disentangle atomic spin dynamics contributions.
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