Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

The GALEX Arecibo SDSS Survey. I. Gas Fraction Scaling Relations of Massive Galaxies and First Data Release

We introduce the GALEX Arecibo SDSS Survey (GASS), an on-going large program that is gathering high quality HI-line spectra using the Arecibo radio telescope for an unbiased sample of ~1000 galaxies with stellar masses greater than 10^10 Msun and redshifts 0.025<z<0.05, selected from the SDSS spectroscopic and GALEX imaging surveys. The galaxies are observed until detected or until a low gas mass fraction limit (1.5-5%) is reached. This paper presents the first Data Release, consisting of ~20% of the final GASS sample. We use this data set to explore the main scaling relations of HI gas fraction with galaxy structure and NUV-r colour. A large fraction (~60%) of the galaxies in our sample are detected in HI. We find that the atomic gas fraction decreases strongly with stellar mass, stellar surface mass density and NUV-r colour, but is only weakly correlated with galaxy bulge-to-disk ratio (as measured by the concentration index of the r-band light). We also find that the fraction of galaxies with significant (more than a few percent) HI decreases sharply above a characteristic stellar surface mass density of 10^8.5 Msun kpc^-2. The fraction of gas-rich galaxies decreases much more smoothly with stellar mass. One of the key goals of GASS is to identify and quantify the incidence of galaxies that are transitioning between the blue, star-forming cloud and the red sequence of passively-evolving galaxies. Likely transition candidates can be identified as outliers from the mean scaling relations between gas fraction and other galaxy properties. [abridged]Comment: 25 pages, 12 figures. Accepted for publication in MNRAS. Version with high resolution figures available at http://www.mpa-garching.mpg.de/GASS/pubs.ph

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Eosinophils are part of the granulocyte response in tuberculosis and promote host resistance in mice

Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. An influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, using complementary genetic models of eosinophil deficiency, we demonstrate that in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice

Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophthalmology, nuclear medicine and endocrinology

BackgroundPostoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement.MethodsA multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations.ResultsConsensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management.ConclusionSalivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163491/2/hed26417.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163491/1/hed26417_am.pd

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

A cross-national mixed-method study of reality pedagogy

This mixed-methods cross-national study investigated the effectiveness of reality pedagogy (an approach in which teachers become part of students’ activities, practices and rituals) in terms of changes in student perceptions of their learning environment and attitudes towards science. A questionnaire was administered to 142 students in grades 8–10 in the Bronx, New York City and Dresden, Germany. The questionnaire combines learning environment scales from the Constructivist Learning Environment Survey and the What Is Happening In this Class? Questionnaire with attitude scales from the Test of Science-Related Attitudes. Student interviews were used to support questionnaire findings. Quantitative data analyses revealed that reality pedagogy had a greater impact on students in the Bronx than in Dresden, with qualitative data clarifying differences in how reality pedagogy was enacted in each geographic area. Overall, our findings add to the body of evidence concerning the effectiveness of reality pedagogy as an approach to teaching and learning science across a variety of contexts. © 2016 Springer Science+Business Media Dordrech

In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells

The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV

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

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