| 1. |
- Culverhouse, R. C., et al.
(författare)
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Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
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| 2. |
- Rana, A., et al.
(författare)
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An edge services framework (esf) for egee, lcg, AND osg
- 2006
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Konferensbidrag (refereegranskat)abstract
- We report on first experiences with building and operating an Edge Services Framework (ESF) based on Xen virtual machines instantiated via the Workspace Service available in Globus Toolkit, and developed as a joint project between EGEE, LCG, and OSG. Many computing facilities are architected with their compute and storage clusters behind firewalls. Edge Services are instantiated on a small set of gateways to provide access to these clusters via standard grid interfaces. Experience on EGEE, LCG, and OSG has shown that at least two issues are of critical importance when designing an infrastructure in support of Edge Services. The first concerns Edge Service configuration. It is impractical to assume that each virtual organization (VO) using a facility will employ the same Edge Service configuration, or that different configurations will coexist easily. Even within a VO, it should be possible to run different versions of the same Edge Service simultaneously. The second issue concerns resource usage: since Edge Services may become a bottleneck to a site, it is essential that an ESF be able to effectively arbitrate resource usage (e.g., memory, CPU, and networking) among different VOs. By providing virtualization on the level of instruction set architecture, virtual machines allow configuration of independent software stacks for each VM executing on a resource. Modern implementations of this abstraction are extremely efficient and have outstanding fine-grained enforcement capabilities. To securely deploy virtual machines, we use the Workspace Service from the Globus Toolkit, which allows a VO administrator to dynamically launch appropriately-configured system images. In addition, we are developing a library of such images, reflecting the needs of presently participating communities ATLAS, CMS, and CDF. We will report on first experiences building and operating this Edge Services Framework.
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| 3. |
- Efimenko, Evgeni, et al.
(författare)
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Analysis of xbx genes in C-elegans
- 2005
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 132:8, s. 1923-1934
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Tidskriftsartikel (refereegranskat)abstract
- Cilia and flagella are widespread eukaryotic subcellular components that are conserved from green algae to mammals. In different organisms they function in cell motility, movement of extracellular fluids and sensory reception. While the function and structural description of cilia and flagella are well established, there are many questions that remain unanswered. In particular, very little is known about the developmental mechanisms by which cilia are generated and shaped and how their components are assembled into functional machineries. To find genes involved in cilia development we used as a search tool a promoter motif, the X-box, which participates in the regulation of certain ciliary genes in the nematode Caenorhabditis elegans. By using a genome search approach for X-box promoter motif-containing genes (xbx genes) we identified a list of about 750 xbx genes (candidates). This list comprises some already known ciliary genes as well as new genes, many of which we hypothesize to be important for cilium structure and function. We derived a C elegans X-box consensus sequence by in vivo expression analysis. We found that xbx gene expression patterns were dependent on particular X-box nucleotide compositions and the distance from the respective gene start. We propose a model where DAF-19, the RFX-type transcription factor binding to the X-box, is responsible for the development of a ciliary module in C elegans, which includes genes for cilium structure, transport machinery, receptors and other factors.
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