A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17

Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant

Applicability of an integrated moving sponge biocarrier-osmotic membrane bioreactor MD system for saline wastewater treatment using highly salt-tolerant microorganisms

© 2017 Elsevier B.V. Osmotic membrane bioreactors (OsMBRs) are a recent breakthrough technology designed to treat wastewater. Nevertheless, their application in high-salinity wastewater treatment is not widespread because of the effects of saline conditions on microbial community activity. In response, this study developed an integrated sponge biocarrier-OsMBR system using highly salt-tolerant microorganisms for treating saline wastewater. Results showed that the sponge biocarrier-OsMBR obtained an average water flux of 2 L/m2 h during a 92-day operation when 1 M MgCl2 was used as the draw solution. The efficiency in removing dissolved organic compounds from the proposed system was more than 99%, and nutrient rejection was close to 100%, indicating excellent performance in simultaneous nitrification and denitrification processes in the biofilm layer on the carriers. Moreover, salt-tolerant microorganisms in the sponge biocarrier-OsMBR system worked efficiently in salt concentrations of 2.4%. A polytetrafluoroethylene MD membrane (pores = 0.45 μm) served to regenerate the diluted draw solution in the closed-loop system and produce high-quality water. The moving sponge biocarrier-OsMBR/MD hybrid system demonstrated its potential to treat salinity wastewater treatment, with 100% nutrient removal and 99.9% conductivity rejection

The design-by-adaptation approach to universal access: learning from videogame technology

This paper proposes an alternative approach to the design of universally accessible interfaces to that provided by formal design frameworks applied ab initio to the development of new software. This approach, design-byadaptation, involves the transfer of interface technology and/or design principles from one application domain to another, in situations where the recipient domain is similar to the host domain in terms of modelled systems, tasks and users. Using the example of interaction in 3D virtual environments, the paper explores how principles underlying the design of videogame interfaces may be applied to a broad family of visualization and analysis software which handles geographical data (virtual geographic environments, or VGEs). One of the motivations behind the current study is that VGE technology lags some way behind videogame technology in the modelling of 3D environments, and has a less-developed track record in providing the variety of interaction methods needed to undertake varied tasks in 3D virtual worlds by users with varied levels of experience. The current analysis extracted a set of interaction principles from videogames which were used to devise a set of 3D task interfaces that have been implemented in a prototype VGE for formal evaluation

Occupational noise exposure is associated with hypertension in China: Results from project ELEFANT

OBJECTIVES: We investigated the association between occupational noise exposure and the risk of elevated blood pressure and hypertension by stage in young adults. METHODS: We utilized 124,286 young adults (18-40 years) from the Project ELEFANT study. We categorized occupational noise exposure as high (75 dBA noise exposure for more than 4 hours per day) or low, and measured blood pressure (mmHg) and categorized participants by hypertension stage (normal, elevated, Stage 1, Stage 2). We applied adjusted logistic regression models to identify associations with hypertension risk, and we further examined the noise-BMI, noise-gender, and noise-residence interactions on hypertension risk in separate models. RESULTS: High occupational noise exposure was associated with increases in blood pressure among participants with elevated blood pressure (Estimate = 0.23, 95% CI: 1.09, 1.46, p = 0.0009), in Stage 1 hypertension (Estimate = 0.15, 95% CI: 1.06, 1.25, p = 0.0008), and in Stage 2 hypertension (Estimate = 0.41 95% CI: 1.31, 1.73, p<0.0001). Likewise, noise exposure-BMI interaction was consistently positively associated with increases in blood pressure in participants with elevated blood pressure (Estimate = 0.71, 95% CI: 1.55, 2.69, p<0.0001), in Stage 1 hypertension (Estimate = 0.78, 95% CI: 1.82, 2.61, p<0.0001), and in Stage 2 hypertension (Estimate = 2.06, 95% CI: 5.64, 10.81, p<0.0001). The noise exposure-male interaction showed higher risk for hypertension compared to the noise exposure-female interaction in participants with elevated blood pressure (Estimate = 1.24, 95% CI: 2.56, 4.71, p<0.0001), Stage 1 (Estimate = 1.67, 95% CI: 4.34, 6.42, p<0.0001) and Stage 2 hypertension (Estimate = 1.70, 95% CI: 3.86, 7.77, p<0.0001). Finally, we found that noise exposure-urban interaction was consistently associated with an increase in blood pressure in elevated blood pressure (Estimate = 0.32, 95% CI: 1.19, 1.62, p<0.0001) and in Stage 2 hypertension (Estimate = 0.44, 95% CI: 1.31, 1.80, p<0.0001)

Depression and anxiety symptoms associated with internet gaming disorder before and during the COVID-19 pandemic: a longitudinal study

Background: The coronavirus disease-2019 (COVID-19) pandemic has profoundly impacted aspects of human life globally. Playing videogames has been encouraged by several organizations to help individuals cope with the COVID-19 pandemic and associated restrictive measures. This longitudinal study was the first to examine gaming in the context of the pandemic and its association with depressive and anxiety symptoms. Methods: The sample comprised 1,778 children and adolescents (50.7% male) who were part of the Project of School Mental Health in Southwest China. Data were collected at two-time intervals: before the COVID-19 pandemic (October to November 2019 – [T1]) and during the COVID-19 pandemic (April to May 2020 – [T2]). Data were collected on perceived COVID-19 impacts, videogame use, Internet Gaming Disorder (IGD), and depressive and anxiety symptoms. Cross-lagged panel models were computed to examine longitudinal relationships. Results: The results indicated that both videogame use and IGD increased significantly for adolescents at T2. The cross-lagged panel model results suggested that depressive and anxiety symptoms at T1 positively predicted IGD and videogame use at T2 (especially for boys), but not inversely. Perceived COVID-19 impacts mediated the relationship between depressive and anxiety symptoms at T1 and IGD at T2. Conclusion: Children and adolescents both increased videogame use at T2, but only adolescents significantly increased IGD severity at T2. The findings supported the compensatory hypothesis, and are consistent with the Interaction of Person-Affect-Cognition-Execution model as individual responses to COVID-19 may function as a mediator between personal predisposing variables and IGD

Turing instabilities in a mathematical model for signaling networks

GTPase molecules are important regulators in cells that continuously run through an activation/deactivation and membrane-attachment/membrane-detachment cycle. Activated GTPase is able to localize in parts of the membranes and to induce cell polarity. As feedback loops contribute to the GTPase cycle and as the coupling between membrane-bound and cytoplasmic processes introduces different diffusion coefficients a Turing mechanism is a natural candidate for this symmetry breaking. We formulate a mathematical model that couples a reaction-diffusion system in the inner volume to a reaction-diffusion system on the membrane via a flux condition and an attachment/detachment law at the membrane. We present a reduction to a simpler non-local reaction-diffusion model and perform a stability analysis and numerical simulations for this reduction. Our model in principle does support Turing instabilities but only if the lateral diffusion of inactivated GTPase is much faster than the diffusion of activated GTPase.Comment: 23 pages, 5 figures; The final publication is available at http://www.springerlink.com http://dx.doi.org/10.1007/s00285-011-0495-

Age at menarche and prevention of hypertension through lifestyle in young Chinese adult women: result from project ELEFANT.

Early and late age at menarche are associated with risk of hypertension, but little is known whether modifiable lifestyle can reduce this risk. METHODS: Our study leverages 60,135 healthy young Chinese women from the Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) study. Menarche age and lifestyle factors were assessed by self-reported questionnaires and hypertension was diagnosed by physicians. We estimated the odds ratios (ORs) of hypertension associated with menarche age using multivariable logistic regression. We further investigated whether modifiable lifestyles (body mass index, BMI; psychological stress; passive smoking; and imbalanced diet) increased risk in joint analyses. RESULTS: The association between age at menarche and hypertension was U-shaped, with age ≤ 12 at menarche giving the highest OR (1.46, 95% confidence interval [CI], 1.27-1.69) and ≥ 16 the second highest (OR = 1.36, 95% CI = 1.15-1.62). Simultaneous analysis of lifestyle risk factors and age of menarche showed that having one or more modifiable risk factors increased the menarche age-hypertension association. The risk of hypertension among participants with menarche age ≤ 12 decreased from OR 13.21 (95% CI = 5.17-29.36) with four high-risk lifestyle factors to 12.36 (95% CI = 9.51-16.05) with three high-risk factors, 5.24 (95% CI = 4.11-6.69) with two, and 2.76 (95% CI = 2.09-3.60) with one, in comparison to individuals with no high-risk lifestyle factors and menarche age 14. CONCLUSIONS: Our results suggest that modification of lifestyle, including maintenance of normal weight and a balanced diet, are associated with substantially reduce the risk of hypertension in high-risk individuals. Early and late age at menarche are risk factors for the development of hypertension in Western populations, and there is limited evidence that this is also true of Chinese populations. Targeted prevention of hypertension in vulnerable populations would be highly beneficial in efforts to reduce the incidence of cardiovascular disease, but it is not currently known whether lifestyle intervention could reduce hypertension risk. In this study, we analysed the risk of hypertension by age at menarche and four modifiable lifestyle factors (BMI, diet, psychological stress, and smoking tobacco) in a cohort of 60,135 young adult Chinese women (mean age 29). We identified that early and late age at menarche are associated with increased risk of hypertension in young Chinese women. There was joint effects between age at menarche and lifestyles on hypertension only participants with age at menarche ≤12 and being overweight or obese. Modification of lifestyle, including maintenance of normal weight and a balanced diet, can substantially reduce the risk of hypertension in high-risk individuals. In conclusion, our study has revealed that early and late menarche age are associated with the development of hypertension in young Chinese women, and that this risk is modified by healthy lifestyle traits

On the ability of spectroscopic SZ effect measurements to determine the temperature structure of galaxy clusters

(abridged) We explore in this paper the ability of spatially resolved spectroscopic measurements of the SZ effect (SZE) to determine the temperature profile of galaxy clusters. We derive a general formalism for the thermal SZE in galaxy clusters with a non-uniform temperature profile that can be applied to both cool-core clusters and non-cool core cluster with an isothermal or non-isothermal temperature structure. We derive an inversion technique through which the electron distribution function can be extracted from spectroscopic SZE observations over a wide frequency range. We study the fitting procedure to extract the cluster temperature from a set of simulated spatially resolved spectroscopic SZE observations in different bands of the spectrum, from 100 to 450 GHz. The results of our analysis for three different cluster prototypes (A2199 with a low-temperature cool core, Perseus with a relatively high-temperature cool core, Ophiuchus with an isothermal temperature distribution) provide both the required precision of the SZE observations and the optimal frequency bands for a determination of the cluster temperature similar or better than that obtainable from X-ray observations. The precision of SZE-derived temperature is also discussed for the outer regions of clusters. We also study the possibility to extract, from our method, the parameters characterizing the non-thermal SZE spectrum of the relativistic plasma contained in the lobes of radio galaxies as well as the spectrum of relativistic electrons co-spatially distributed with the thermal plasma in clusters with non-thermal phenomena. We find that the next generation SZE experiments with spectroscopic capabilities can provide precise temperature distribution measurements (...)Comment: Submitted to Astronomy & Astrophysic