Genome-wide analysis of acute low salinity tolerance in the eastern oyster Crassostrea virginica and potential of genomic selection for trait improvement

As the global demand for seafood increases, research into the genetic basis of traits that can increase aquaculture production is critical. The eastern oyster (Crassostrea virginica) is an important aquaculture species along the Atlantic and Gulf Coasts of the United States, but increases in heavy rainfall events expose oysters to acute low salinity conditions, which negatively impact production. Low salinity survival is known to be a moderately heritable trait, but the genetic architecture underlying this trait is still poorly understood. In this study, we used ddRAD sequencing to generate genome-wide single-nucleotide polymorphism (SNP) data for four F2 families to investigate the genomic regions associated with survival in extreme low salinity (\u3c3). SNP data were also used to assess the feasibility of genomic selection (GS) for improving this trait. Quantitative trait locus (QTL) mapping and combined linkage disequilibrium analysis revealed significant QTL on eastern oyster chromosomes 1 and 7 underlying both survival and day to death in a 36-day experimental challenge. Significant QTL were located in genes related to DNA/RNA function and repair, ion binding and membrane transport, and general response to stress. GS was investigated using Bayesian linear regression models and prediction accuracies ranged from 0.48 to 0.57. Genomic prediction accuracies were largest using the BayesB prior and prediction accuracies did not substantially decrease when SNPs located within the QTL region on Chr1 were removed, suggesting that this trait is controlled by many genes of small effect. Our results suggest that GS will likely be a viable option for improvement of survival in extreme low salinity

Indoor air pollution exposure from use of indoor stoves and fireplaces in association with breast cancer: a case-control study

Background: Previous studies suggest that polycyclic aromatic hydrocarbons (PAHs) may adversely affect breast cancer risk. Indoor air pollution from use of indoor stoves and/or fireplaces is an important source of ambient PAH exposure. However, the association between indoor stove/fireplace use and breast cancer risk is unknown. We hypothesized that indoor stove/fireplace use in a Long Island, New York study population would be positively associated with breast cancer and differ by material burned, and the duration and timing of exposure. We also hypothesized that the association would vary by breast cancer subtype defined by p53 mutation status, and interact with glutathione S-transferases GSTM1, T1, A1 and P1 polymorphisms. Methods: Population-based, case-control resources (1,508 cases/1,556 controls) were used to conduct unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Breast cancer risk was increased among women reporting ever burning synthetic logs (which may also contain wood) in their homes (OR = 1.42, 95% CI 1.11, 1.84), but not for ever burning wood alone (OR = 0.93, 95% CI 0.77, 1.12). For synthetic log use, longer duration >7 years, older age at exposure (>20 years; OR = 1.65, 95% CI 1.02, 2.67) and 2 or more variants in GSTM1, T1, A1 or P1 (OR = 1.71, 95% CI 1.09, 2.69) were associated with increased risk. Conclusions: Burning wood or synthetic logs are both indoor PAH exposure sources; however, positive associations were only observed for burning synthetic logs, which was stronger for longer exposures, adult exposures, and those with multiple GST variant genotypes. Therefore, our results should be interpreted with care and require replication. Electronic supplementary material The online version of this article (doi:10.1186/1476-069X-13-108) contains supplementary material, which is available to authorized users

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.</p> <p>Objective</p> <p>To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).</p> <p>A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.</p> <p>Methods</p> <p>A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.</p> <p>Results</p> <p>There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).</p> <p>Conclusion</p> <p>The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.</p

Harnessing citizen science through mobile phone technology to screen for immunohistochemical biomarkers in bladder cancer

Background: Immunohistochemistry (IHC) is often used in personalisation of cancer treatments. Analysis of large data sets to uncover predictive biomarkers by specialists can be enormously time-consuming. Here we investigated crowdsourcing as a means of reliably analysing immunostained cancer samples to discover biomarkers predictive of cancer survival. Methods: We crowdsourced the analysis of bladder cancer TMA core samples through the smartphone app ‘Reverse the Odds’. Scores from members of the public were pooled and compared to a gold standard set scored by appropriate specialists. We also used crowdsourced scores to assess associations with disease-specific survival. Results: Data were collected over 721 days, with 4,744,339 classifications performed. The average time per classification was approximately 15 s, with approximately 20,000 h total non-gaming time contributed. The correlation between crowdsourced and expert H-scores (staining intensity × proportion) varied from 0.65 to 0.92 across the markers tested, with six of 10 correlation coefficients at least 0.80. At least two markers (MRE11 and CK20) were significantly associated with survival in patients with bladder cancer, and a further three markers showed results warranting expert follow-up. Conclusions: Crowdsourcing through a smartphone app has the potential to accurately screen IHC data and greatly increase the speed of biomarker discovery

EXAMINING THE GENETIC BASIS AND PHYSIOLOGY OF SURVIVAL IN EXTREME LOW SALINITY TO IMPROVE AQUACULTURE OF THE EASTERN OYSTER Crassostrea virginica

The eastern oyster, Crassostrea virginica, is an important aquaculture species and supports a growing industry along the east coast of the United States. However, increases in freshwater from storm events and intentional diversions can expose coastal aquaculture operations to extreme low salinity (< 5), resulting in reduced productivity and mortality. The primary objectives of this dissertation were to investigate the biology and genetic basis of low salinity tolerance to improve eastern oyster aquaculture. In Chapter 2, I developed and conducted a series of extreme low salinity (2.5) challenges to estimate the quantitative genetic parameters of low salinity survival. A moderate narrow-sense heritability was estimated for challenge survival, h2 ≈ 0.4. In addition, osmolality of hemolymph collected from oysters during the first week of the challenge suggest that all individuals conformed to the surrounding low salinity regardless of challenge survival. In Chapter 3, I performed additional low salinity challenges to assess the importance of challenge duration (2 or 6 months) and temperature (chronic or fluctuating) on low salinity survival. I also investigated algae removal during the chronic challenge to better understand oyster response during low salinity stress. Phenotypic (rS = 0.89) and genetic (rG = 0.81) correlations between family mortality were high across the two challenges, indicating that a 30-day exposure at a constant low salinity (2.5) and temperature (27°C) is a sufficient progeny test for low salinity survival. Modest associations between algae removal metrics and survival in extreme low salinity indicate that individual feeding ability may relate to differential low salinity survival. Lastly, in Chapter 4, I performed genome mapping to investigate the genomic architecture of low salinity survival. Quantitative trait locus mapping and linkage disequilibrium analysis revealed a significant region on eastern oyster chromosome 1 and 7. Genomic prediction accuracies for survival and day to death in extreme low salinity were moderate and encouraging, 0.49 – 0.57. The results from my dissertation characterize the genetic basis of survival during low salinity events and support the incorporation of this trait into breeding efforts to improve production and enhance the resiliency of the eastern oyster aquaculture industry

Modeling the Impact of Simulated Educational Interventions on the Use and Abuse of Pharmaceutical Opioids in the United States: A Report on Initial Efforts

Three educational interventions were simulated in a system dynamics model of the medical use, trafficking, and nonmedical use of pharmaceutical opioids. The study relied on secondary data obtained in the literature for the period of 1995 to 2008 as well as expert panel recommendations regarding model parameters and structure. The behavior of the resulting systems-level model was tested for fit against reference behavior data. After the base model was tested, logic to represent three educational interventions was added and the impact of each intervention on simulated overdose deaths was evaluated over a 7-year evaluation period, 2008 to 2015. Principal findings were that a prescriber education intervention not only reduced total overdose deaths in the model but also reduced the total number of persons who receive opioid analgesic therapy, medical user education not only reduced overdose deaths among medical users but also resulted in increased deaths from nonmedical use, and a “popularity” intervention sharply reduced overdose deaths among nonmedical users while having no effect on medical use. System dynamics modeling shows promise for evaluating potential interventions to ameliorate the adverse outcomes associated with the complex system surrounding the use of opioid analgesics to treat pain