Variation in _PNPLA3_ is associated with outcomes in alcoholic liver disease

Two recent genome-wide association studies have described associations of SNP variants in _PNPLA3_ with nonalcoholic fatty liver and plasma liver enzyme levels in population based cohorts. We investigated the contributions of these variants to clinical outcomes in Mestizo subjects with a history of excessive alcohol consumption. We show that non-synonymous variant rs738409[G] (I148M) in _PNPLA3_ is strongly associated with alcoholic liver disease and progression to alcoholic cirrhosis (unadjusted OR = 2.25, P = 1.7x10^-10^; ancestry-adjusted OR = 1.79, P = 1.9x10^-5^)

Addition of the direct radiative effect of atmospheric aerosols into the Regional Atmospheric Modeling System (RAMS), The

Includes bibliographical references.DoD Center for Geosciences/Atmospheric Research under grant DAAD19-02-2-0005

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease-Causing Point Mutations

Despite intense study of the neurofibromatosis type 2 (NF2) tumor-suppressor protein merlin, the biological properties and tumor-suppressor functions of merlin are still largely unknown. In this study, we examined the molecular activities of NF2-causing mutant merlin proteins in transfected mammalian cells, to elucidate the merlin properties that are critical for tumor-suppressor function. Most important, we found that 80% of the merlin mutants studied significantly altered cell adhesion, causing cells to detach from the substratum. This finding implies a function for merlin in regulating cell-matrix attachment, and changes in cell adhesion caused by mutant protein expression may be an initial step in the pathogenesis of NF2. In addition, five different mutations in merlin caused a significant increase in detergent solubility of merlin compared to wild type, indicating a decreased ability to interact with the cytoskeleton. Although not correlated to the cell-adhesion phenotype, four missense mutations decreased the binding of merlin to the ERM-interacting protein EBP-50, implicating this interaction in merlin inhibition of cell growth. Last, we found that some NF2 point mutations in merlin most closely resembled gain-of-function alleles in their cellular phenotype, which suggests that mutant NF2 alleles may not always act in a loss-of-function manner, as had been assumed, but may include a spectrum of allelic types with different phenotypic effects on the function of the protein. In aggregate, these cellular phenotypes provide a useful assay for identifying the functional domains and molecular partners necessary for merlin tumor-suppressor activity

Clinical validity assessment of a breast cancer risk model combining genetic and clinical information

_Background:_ The extent to which common genetic variation can assist in breast cancer (BCa) risk assessment is unclear. We assessed the addition of risk information from a panel of BCa-associated single nucleotide polymorphisms (SNPs) on risk stratification offered by the Gail Model.

_Methods:_ We selected 7 validated SNPs from the literature and genotyped them among white women in a nested case-control study within the Women’s Health Initiative Clinical Trial. To model SNP risk, previously published odds ratios were combined multiplicatively. To produce a combined clinical/genetic risk, Gail Model risk estimates were multiplied by combined SNP odds ratios. We assessed classification performance using reclassification tables and receiver operating characteristic (ROC) curves. 

_Results:_ The SNP risk score was well calibrated and nearly independent of Gail risk, and the combined predictor was more predictive than either Gail risk or SNP risk alone. In ROC curve analysis, the combined score had an area under the curve (AUC) of 0.594 compared to 0.557 for Gail risk alone. For reclassification with 5-year risk thresholds at 1.5% and 2%, the net reclassification index (NRI) was 0.085 (Z = 4.3, P = 1.0×10^-5^). Focusing on women with Gail 5-year risk of 1.5-2% results in an NRI of 0.195 (Z = 3.8, P = 8.6×10^−5^).

_Conclusions:_ Combining clinical risk factors and validated common genetic risk factors results in improvement in classification of BCa risks in white, postmenopausal women. This may have implications for informing primary prevention and/or screening strategies. Future research should assess the clinical utility of such strategies.
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Division I College Athletes’ Self-Perception: Investigating the Impact of Race and Discrimination

Self-perception is the level of competency at which individuals evaluate themselves in certain areas or domains (Marsh & Shavelson, 1985). An individual’s self-perceptions contribute to their global self-worth and even predicts performance (Cuellar, 2014; Harter & Neemann, 2012). This study measures self-perception scores, as well as experiences with racial discrimination, of 306 NCAA Division I college athletes using the Self-Perception Profile for College Students (Harter & Neemann, 2012). Scores are compared across race. Findings suggest that White college athletes have significantly higher self-perception scores than college athletes of color - with recent discrimination (within the last year) as a significant predictor of multiple areas of self-perception. The implications of this study suggest that faculty and other campus stakeholders should pursue positive relationships with the college athletes they encounter. Positive relationships between college athletes and faculty may help raise college athlete self-perceptions, and in turn, performance in a variety of areas

Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

10.1371/journal.pone.0053830PLoS ONE81

IxPopDyMod: an R package to write, run, and analyze tick population and infection dynamics models

Abstract Given the increasing prevalence of tick-borne diseases, such as Lyme disease, modeling the population and infection dynamics of tick vectors is an important public health tool. These models have applications for testing the effects of control methods or climate change on tick populations. There is an established history of tick population models, but code for them is rarely shared, especially not in a convenient format for others to modify and use. We present an R package, called IxPopDyMod, intended to function as a flexible and consistent framework for reproducible Ixodidae (hard-bodied ticks) population dynamics models. Here we focus on two key parts of the package: a function to create valid model configurations and a function to run a configured model and return the daily population over time. We provide three examples in appendices: one reproducing an existing Ixodes scapularis population model, one providing a novel Dermacentor albipictus model, and one showing Borrelia burgdorferi infection in ticks. Together these examples show the flexibility of the package to model scenarios of interest to tick researches. Graphical Abstrac