Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy

Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule

Effect of Exogenous Fibrolytic Enzymes Supplementation or Functional Feed Additives on In Vitro Ruminal Fermentation of Chemically Pre-Treated Sunflower Heads

peer reviewedThis study aims to provide possible utilization of sunflower head byproduct (SFH) as a feedstuff by implementing chemical pretreatments (4% sodium hydroxide (SFHNaOH) or 4% urea (SFHurea) and supplementation with either exogenous fibrolytic enzymes (EFE) or functional feed additive (FFA). The experimental EFE was a complex (1:1, v/v) of two enzyme products with high activity of β-1,3-1,4-glucanase and endo-1,4-β-D-xylanase and applied at 0 (SFHout), 1, 2, 5, and 10 µL/ gdry matter, while FFA was a fermentation byproduct rich in cellulase and xylanase activities, applied at 0 (SFHout), 0.5, 1, 2, and 4 mg/g DM. SFHurea had the highest (p < 0.05) crude protein (CP) content compared to other SFH substrates. Linear enhancements (p < 0.05) in kinetics of gas production (GP), metabolizable energy (ME), organic matter digestibility (OMD) and total short-chain fatty acids (SCFAs) concentrations were observed for all SFH substrates supplemented with EFE. The SFHout had the highest (p < 0.05) potential GP, maximum rate (Rmax) of GP, ME, OMD and SCFAs. Supplementation of EFE was more pronounced than FFA in affecting the kinetic parameters of in vitro GP for all SFH substrates. SFHout supplemented with EFE seems to be the most promising substrate to enhance microbial fermentation in vitro

Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the ‘TxArray’, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0211-x) contains supplementary material, which is available to authorized users

Protein phosphatase 2A family members (PP2A and PP6) associate with U1 snRNP and the spliceosome during pre-mRNA splicing

Abstract Protein phosphorylation and dephosphorylation are both important for multiple steps in the splicing pathway. Members of the PP1 and PP2A subfamilies of phospho-serine/threonine phosphatases play essential but redundant roles in the second step of the splicing reaction. PP6, a member of the PP2A subfamily, is the mammalian homologue of yeast Sit4p and ppe1, which are involved in cell cycle regulation; however, the involvement of PP6 in the splicing pathway remains unclear. Here we show that PP2A family members physically associate with the spliceosome throughout the splicing reaction. PP2A holoenzyme and PP6 were found stably associated with U1 snRNP. Together our findings indicate that these phosphatases regulate splicing catalysis involving U1 snRNP and suggest an important evolutionary conserved role of PP2A family phosphatases in pre-mRNA splicing