Nitric Oxide and Cnidarian-Dinoflagellate Symbioses: Pieces of a Puzzle

The presence of nitric oxide synthase (NOS) activity is demonstrated in the tropical marine cnidarian Aiptasia pallida and in its symbiotic dinoflagellate algae, Symbiodinium bermudense. Enzyme activity was assayed by measuring the conversion of arginine to citrulline. Biochemical characterization of NOS from Aiptasia was characterized with respect to cellular localization, substrate and cofactor requirements, inhibitors, and kinetics. In response to acute temperature shock, anemones retracted their tentacles. Animals subjected to such stress had lower NOS activities than did controls. Treatment with NOS inhibitors caused tentacular retraction, while treatment with the NOS substrate L-arginine inhibited this response to stress, as did treatment with NO donors. These results provide a preliminary biochemical characterization of, and suggest a functional significance for, NOS activity in anthozoan-algal symbiotic assemblages

Empirical Bayes accomodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients

<p>Abstract</p> <p>Background</p> <p>Non-biological experimental error routinely occurs in microarray data collected in different batches. It is often impossible to compare groups of samples from independent experiments because batch effects confound true gene expression differences. Existing methods can correct for batch effects only when samples from all biological groups are represented in every batch.</p> <p>Results</p> <p>In this report we describe a generalized empirical Bayes approach to correct for cross-experimental batch effects, allowing direct comparisons of gene expression between biological groups from independent experiments. The proposed experimental design uses identical reference samples in each batch in every experiment. These reference samples are from the same tissue as the experimental samples. This design with tissue matched reference samples allows a gene-by-gene correction to be performed using fewer arrays than currently available methods. We examine the effects of non-biological variation within a single experiment and between experiments.</p> <p>Conclusion</p> <p>Batch correction has a significant impact on which genes are identified as differentially regulated. Using this method, gene expression in the blood of patients with Duchenne Muscular Dystrophy is shown to differ for hundreds of genes when compared to controls. The numbers of specific genes differ depending upon whether between experiment and/or between batch corrections are performed.</p

Comparative Analysis of Teleost Genome Sequences Reveals an Ancient Intron Size Expansion in the Zebrafish Lineage

We have developed a bioinformatics pipeline for the comparative evolutionary analysis of Ensembl genomes and have used it to analyze the introns of the five available teleost fish genomes. We show our pipeline to be a powerful tool for revealing variation between genomes that may otherwise be overlooked with simple summary statistics. We identify that the zebrafish, Danio rerio, has an unusual distribution of intron sizes, with a greater number of larger introns in general and a notable peak in the frequency of introns of approximately 500 to 2,000 bp compared with the monotonically decreasing frequency distributions of the other fish. We determine that 47% of D. rerio introns are composed of repetitive sequences, although the remainder, over 331 Mb, is not. Because repetitive elements may be the origin of the majority of all noncoding DNA, it is likely that the remaining D. rerio intronic sequence has an ancient repetitive origin and has since accumulated so many mutations that it can no longer be recognized as such. To study such an ancient expansion of repeats in the Danio, lineage will require further comparative analysis of fish genomes incorporating a broader distribution of teleost lineages

Mobility, risk behavior and HIV/STI rates among female sex workers in Kaiyuan City, Yunnan Province, China

<p>Abstract</p> <p>Background</p> <p>The mobility of female sex workers (FSWs) is a factor in the geographic spread of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study describes FSW mobility patterns in a high risk area of China to identify factors associated with increased mobility, and to study the incidence and prevalence of HIV/STIs in this group.</p> <p>Methods</p> <p>270 FSWs recruited from a baseline cross-sectional study were invited to participate in a one-year monthly follow-up cohort study in Kaiyuan City, Yunnan Province, China from 2006 to 2007. Laboratory tests were conducted for HIV/STIs at baseline, 6 and 12 months.</p> <p>Results</p> <p>A total of 117 (43.3%) FSWs moved to another city during the year. Risk factors for increased mobility included being from another city within Yunnan (adjusted hazard ratio [AHR] 1.67, 95% confidence interval [CI] 1.09-2.56), being from outside Yunnan (AHR 1.58, 95% CI 1.04-2.54), and working in lower risk entertainment establishments (AHR 1.55, 95% CI 1.03-2.35). HIV-positive subjects, drug users and FSWs in higher risk venue were less likely to change residence, less likely to use condoms with clients, and earned less per client, but had more working locations and more clients each month.</p> <p>Conclusions</p> <p>The least mobile FSWs were from Kaiyuan, worked in higher risk venues, were more likely to use drugs and be HIV-infected. Because FSWs characteristics differ according to the venue at which they work, future prevention work should tailor programs according to venue with a particular focus on FSWs in higher risk venues.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment