Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available

Author Correction: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Effect of Process Parameters and Shot Peening on the Tensile Strength and Deflection of Polymer Parts Made Using Mask Image Projection Stereolithography (MIP-SLA)

Mask Image Projection Stereolithography (MIP-SLA) is an additive manufacturing technique in which a liquid photopolymer resin is hardened from exposure to ultraviolet (UV) light. Shot peening is a surface treatment to improve the mechanical properties of components. The goal of this work was to quantify the effect of SLA print process parameters, namely layer height and UV exposure, and shot peening on the longitudinal tensile strength of ASTM D638 Type 5 test artifacts. Test parts were created using a central composite experimental plan on a B9 Creator desktop SLA machine. Deflection of the pseudo-Almen strips after shot peening was measured using a digital camera to identify desired peening condition. Post-shot peening tensile strength was measured for the ASTM D638 Type 5 parts. Shot peening generally decreased the strength of MIPSLA parts.Mechanical Engineerin