Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups.

The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of “an attack” on GWAS data by Homer et al. [1]. Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. [2] proposed new methods to release aggregate GWAS data without compromising an individual's privacy. We extend the methods developed in [2] for releasing differentially-private χ2-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls’ data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov [3].

BackgroundThe relationship between ambient air pollution exposure and mortality of cardiovascular and cerebrovascular diseases in human is controversial, and there is little information about how exposures to ambient air pollution contribution to the mortality of cardiovascular and cerebrovascular diseases among Chinese. The aim of the present study was to examine whether exposure to ambient-air pollution increases the risk for cardiovascular and cerebrovascular disease.Methodology/Principal FindingsWe conducted a retrospective cohort study among humans to examine the association between compound-air pollutants [particulate matter <10 µm in aerodynamic diameter (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2)] and mortality in Shenyang, China, using 12 years of data (1998–2009). Also, stratified analysis by sex, age, education, and income was conducted for cardiovascular and cerebrovascular mortality. The results showed that an increase of 10 µg/m3 in a year average concentration of PM10 corresponds to 55% increase in the risk of a death cardiovascular disease (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.51 to 1.60) and 49% increase in cerebrovascular disease (HR, 1.49; 95% CI, 1.45 to 1.53), respectively. The corresponding figures of adjusted HR (95%CI) for a 10 µg/m3 increase in NO2 was 2.46 (2.31 to 2.63) for cardiovascular mortality and 2.44 (2.27 to 2.62) for cerebrovascular mortality, respectively. The effects of air pollution were more evident in female that in male, and nonsmokers and residents with BMI<18.5 were more vulnerable to outdoor air pollution.Conclusion/SignificanceLong-term exposure to ambient air pollution is associated with the death of cardiovascular and cerebrovascular diseases among Chinese populations.

Background: In China, both the levels and patterns of outdoor air pollution have altered dramatically with the rapid economic development and urbanization over the past two decades. However, few studies have investigated the association of outdoor air pollution with respiratory mortality, especially in the high pollution range. Objective: We conducted a retrospective cohort study of 9,941 residents aged ≥35 years old in Shenyang, China, to examine the association between outdoor air pollutants [particulate matter <10 µm in aerodynamic diameter (PM₁₀), sulfur dioxide (SO₂) and nitrogen dioxide (NO₂)] and mortality using 12 years of data. Methods: We applied extended Cox proportional hazards modeling with time-dependent covariates to respiratory mortality. Analyses were also stratified by age, sex, educational level, smoking status, personal income, occupational exposure and body mass index (BMI) to examine the association of air pollution with mortality. Results: We found significant associations between PM₁₀ and NO₂ levels and respiratory disease mortality. Our analysis found a relative risk of 1.67 [95% confidence interval (CI) 1.60–1.74] and 2.97 (95% CI 2.69–3.27) for respiratory mortality per 10 µg/m³ increase in PM₁₀ and NO₂, respectively. The effects of air pollution were more apparent in women than in men. Age, sex, educational level, smoking status, personal income, occupational exposure, BMI and exercise frequency influenced the relationship between outdoor PM₁₀ and NO₂ and mortality. For SO₂, only smoking, little regular exercise and BMI above 18.5 influenced the relationship with mortality. Conclusion: These data contribute to the scientific literature on the long-term effects of air pollution for the high-exposure settings typical in developing countries.

Mechanistic target of rapamycin mTOR complex 1 (mTORC1) plays a key role in the integration of various environmental signals to regulate cell growth and metabolism. mTORC1 is recruited to the lysosome where it is activated by its interaction with GTP-bound Rheb GTPase. However, the regulatory mechanism of Rheb activity remains largely unknown. Here, we show that ubiquitination governs the nucleotide-bound status of Rheb. Lysosome-anchored E3 ligase RNF152 catalyzes Rheb ubiquitination and promotes its binding to the TSC complex. EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation, leading to the release of Rheb from the TSC complex. Functionally, ubiquitination of Rheb is linked to mTORC1-mediated signaling and  consequently regulates tumor growth. Thus, we propose a mechanistic model whereby Rheb–mediated mTORC1 activation is dictated by a dynamic opposing act between Rheb ubiquitination and deubiquitination that are catalyzed by RNF152 and USP4 respectively.