| 5831. |
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| 5832. |
- Rioux, JD, et al.
(författare)
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Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 106:44, s. 18680-18685
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Tidskriftsartikel (refereegranskat)abstract
- The human MHC represents the strongest susceptibility locus for autoimmune diseases. However, the identification of the true predisposing gene(s) has been handicapped by the strong linkage disequilibrium across the region. Furthermore, most studies to date have been limited to the examination of a subset of the HLA and non-HLA genes with a marker density and sample size insufficient for mapping all independent association signals. We genotyped a panel of 1,472 SNPs to capture the common genomic variation across the 3.44 megabase (Mb) classic MHC region in 10,576 DNA samples derived from patients with systemic lupus erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate control samples. We identified the primary association signals for each disease and performed conditional regression to identify independent secondary signals. The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region.
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| 5833. |
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| 5834. |
- Ritz, R, et al.
(författare)
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A new software center for the neuroinformatics community
- 2008
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Konferensbidrag (refereegranskat)abstract
- The mission of the International Neuroinformatics Coordinating Facility is to coordinate and foster international activities in neuroinformatics. In general, this includes combining neuroscience and informatics research to develop and apply advanced tools and approaches essential for a major advancement in understanding the structure and function of the brain. There are a significant number of resources available for neuroscientists today, yet they are not used as widely as they should because discovering their existence and evaluating their quality and relevance remain tedious tasks. Furthermore, the development of such resources often relies on isolated laboratories where collaboration across projects would be beneficial. INCF has therefore created a Neuroinformatics Portal, and released a Software Center as its first component.
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| 5835. |
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| 5836. |
- Rodziewicz-Motowidlo, S, et al.
(författare)
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Checking the conformational stability of cystatin C and its L68Q variant by molecular dynamics studies: Why is the L68Q variant amyloidogenic?
- 2006
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Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1095-8657 .- 1047-8477. ; 154:1, s. 68-78
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Tidskriftsartikel (refereegranskat)abstract
- Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its native state it is a monomer with alpha/beta structure. Experimental evidence suggests that L68Q variant associates into dimeric intermediates and that the dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils. Details of the pathway of L68Q mutant amyloid formation are unclear; however, different experimental approaches with resolutions at molecular level have provided Some clues. Probably, the stability and flexibility of monomeric L68Q variant play essential roles in the early steps of amyloid formation; thus, it is necessary to characterize early conformational changes of L68Q cystatin C monomers. In this paper, we demonstrate the possibility that the differences between the monomeric forms of wild-type (wt) cystatin C and its L68Q variant are responsible for higher tendency of the L68Q cystatin C amyloidogenesis. We started our studies with the simulations of wt and L68Q cystatin C monomers. Nanosecond time scale molecular dynamics simulations at 308 K were performed using AMBER7.0 program, The results show that the structure of the L68Q monomer was changed, relative to the wt cystatin C structure. The results support earlier speculation that the L68Q point mutation would easily lead to dimer formation. (c) 2006 Published by Elsevier Inc.
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| 5837. |
- Roose, Benjamin W., et al.
(författare)
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A Structural Basis for Xe-129 Hyper-CEST Signal in TEM-1 beta-Lactamase
- 2019
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Ingår i: ChemPhysChem. - : WILEY-V C H VERLAG GMBH. - 1439-4235 .- 1439-7641. ; 20:2, s. 260-267
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Tidskriftsartikel (refereegranskat)abstract
- Genetically encoded (GE) contrast agents detectable by magnetic resonance imaging (MRI) enable non-invasive visualization of gene expression and cell proliferation at virtually unlimited penetration depths. Using hyperpolarized Xe-129 in combination with chemical exchange saturation transfer, an MR contrast approach known as hyper-CEST, enables ultrasensitive protein detection and biomolecular imaging. GE MRI contrast agents developed to date include nanoscale proteinaceous gas vesicles as well as the monomeric bacterial proteins TEM-1 beta-lactamase (bla) and maltose binding protein (MBP). To improve understanding of hyper-CEST NMR with proteins, structural and computational studies were performed to further characterize the Xe-bla interaction. X-ray crystallography validated the location of a high-occupancy Xe binding site predicted by MD simulations, and mutagenesis experiments confirmed this Xe site as the origin of the observed CEST contrast. Structural studies and MD simulations with representative bla mutants offered additional insight regarding the relationship between local protein structure and CEST contrast.
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| 5838. |
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| 5839. |
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| 5840. |
- Ropponen, A, et al.
(författare)
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Night Work and Sustainable Working Life-A Prospective Trajectory Analysis of Swedish Twins
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:17
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the changes in sustainable working life over 10–13 years of follow-up and the effect of baseline night work. Data from the Swedish national registers were used to define sustainable working life. Survey data in the 1998–2003 “SALT” with 34,680 twins or in the 2004–2006 “STAGE” with 19,637 twins were utilized to assess night work at baseline. Group-based trajectory and multinomial regression models were applied. The results of the SALT cohort yielded five trajectory solutions: stable sustainable working life (40%), stable lack of sustainable working life (25%), later decreasingly sustainable working life (15%), increasingly sustainable working life (14%), and early decreasingly sustainable working life (7%). In the STAGE cohort, four trajectories were detected: stable sustainable working life (83%), decreasingly sustainable working life (7%), stable lack of sustainable working life (5%), and increasing sustainable working life (5%). Night work was associated with the decreasing or increasing sustainable working life in the trajectory groups. To conclude, the largest parts of both cohorts followed trajectories of stable sustainable working lives. Night work was associated with both the trajectories of decreasing and increasing sustainable working lives.
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