Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease

Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed.     

Identification and characterization of a bovine sperm protein that binds specifically to single-stranded telomeric deoxyribonucleic acid

Telomere DNA at the physical termini of chromosomes forms a single-stranded 3' overhang. In lower eukaryotes, e.g., ciliated protozoa, this DNA extension is capped by specific proteins that have been structurally and functionally characterized. Much less is known about single-stranded telomere DNA-binding proteins in vertebrates. Here we describe a new protein from bovine sperm designated bsSSTBP that specifically interacts with single-stranded (TTAGGG)(N) DNA. The bsSSTBP was extracted from nuclei by 0.6 M KCl. The native size of this protein, estimated by gel filtration, was 20-40 kDa. SDS-PAGE of the UV cross-linked complex between bsSSTBP and telomere DNA indicated that several polypeptides are involved in complex formation. Bovine sSSTB had high specificity toward nucleotide sequence, since single nucleotide substitutions in the (TTAGGG)(4) substrate suppressed binding. The minimal number of (TTAGGG) repeats required for binding of bsSSTBP was 3, and the protein recognized linear but not folded DNA structures. We propose that the bsSSTBP participates in telomere-telomere interactions and the telomere membrane localization observed in mature sperm. In mammals, somatic telomere-binding proteins are apparently substituted by sperm-specific ones that may lead to a structural reorganization of telomere domains to fulfill functions important during meiosis and fertilization.     

Oceanographic variation influences spatial genomic structure in the sea scallop,Placopecten magellanicus

Environmental factors can influence diversity and population structure in marine species and accurate understanding of this influence can both improve fisheries management and help predict responses to environmental change. We used 7163 SNPs derived from restriction site‐associated DNA sequencing genotyped in 245 individuals of the economically important sea scallop, Placopecten magellanicus, to evaluate the correlations between oceanographic variation and a previously identified latitudinal genomic cline. Sea scallops span a broad latitudinal area (>10 degrees), and we hypothesized that climatic variation significantly drives clinal trends in allele frequency. Using a large environmental dataset, including temperature, salinity, chlorophyll a, and nutrient concentrations, we identified a suite of SNPs (285–621, depending on analysis and environmental dataset) potentially under selection through correlations with environmental variation. Principal components analysis of different outlier SNPs and environmental datasets revealed similar northern and southern clusters, with significant associations between the first axes of each (R²_adj = .66–.79). Multivariate redundancy analysis of outlier SNPs and the environmental principal components indicated that environmental factors explained more than 32% of the variance. Similarly, multiple linear regressions and random‐forest analysis identified winter average and minimum ocean temperatures as significant parameters in the link between genetic and environmental variation. This work indicates that oceanographic variation is associated with the observed genomic cline in this species and that seasonal periods of extreme cold may restrict gene flow along a latitudinal gradient in this marine benthic bivalve. Incorporating this finding into management may improve accuracy of management strategies and future predictions.