Scientists publishing in PLoS Biology this week have used stable isotope labeling with amino acids in cell culture (SILAC) and subsequent mass spec to screen the human proteome for possible targets of γ-secretase and found a small number of new substrates, all of which are type I transmembrane proteins with diverse biological roles. In a related paper, Italian computational researchers used a predictive algorithm to analyze the propensity of 34,180 human protein sequences to form amyloid-like fibrils. They found that most do, and that the process occurs generally, depending on various subcellular factors. Their work was in last week's PLoS Computational Biology.
Last week Bing Ren's UCSD lab also published work in PLoS Computational Biology that used an unsupervised learning method called ChromaSig to find commonly occurring chromatin signatures in tiling microarray and sequencing data. Applying this to nine chromatin marks across one percent of the human genome in HeLa cells, they found eight clusters of distinct chromatin signatures, "five of which correspond to known patterns associated with transcriptional promoters and enhancers."
Two papers study exon splicing. In PLoS Genetics last week, scientists looked at the splicing patterns of Alu elements in human tissues. By using exon array data of 330 Alu-derived exons in 11 human tissues and RT-PCR on 38 exons, they showed that some Alu-derived exons are always spliced while some have a tissue-specific switch. Collaborating scientists in India and Wisconsin examine the evolution of the split structure in long, protein-coding genes. By looking at ORF length constraints in the genomes of nine different species, they suggest these may have evolved "due to the indigenous occurrence of split protein-coding genes in primordial random nucleotide sequence," they write in PLoS One.
In PloS Medicine, investigators published results from the Strategies for Management of Anti-Retroviral Therapy (SMART) trial, which looked at biomarkers for success or failure in giving HIV-positive patients alternate forms of anti-retroviral therapy. Studying six biomarkers for the presence of inflammation or increased coagulation in stored blood samples from the 85 people who died during the SMART trial and from 170 survivor controls, they found that IL-6 and D-dimer levels increase the risk of death following interrupted ART.
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