Climate change promotes parasitism in a coral symbiosis.

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Benchmarking natural-language parsers for biological applications using dependency graphs

BACKGROUND: Interest is growing in the application of syntactic parsers to natural language processing problems in biology, but assessing their performance is difficult because differences in linguistic convention can falsely appear to be errors. We present a method for evaluating their accuracy using an intermediate representation based on dependency graphs, in which the semantic relationships important in most information extraction tasks are closer to the surface. We also demonstrate how this method can be easily tailored to various application-driven criteria. RESULTS: Using the GENIA corpus as a gold standard, we tested four open-source parsers which have been used in bioinformatics projects. We first present overall performance measures, and test the two leading tools, the Charniak-Lease and Bikel parsers, on subtasks tailored to reflect the requirements of a system for extracting gene expression relationships. These two tools clearly outperform the other parsers in the evaluation, and achieve accuracy levels comparable to or exceeding native dependency parsers on similar tasks in previous biological evaluations. CONCLUSION: Evaluating using dependency graphs allows parsers to be tested easily on criteria chosen according to the semantics of particular biological applications, drawing attention to important mistakes and soaking up many insignificant differences that would otherwise be reported as errors. Generating high-accuracy dependency graphs from the output of phrase-structure parsers also provides access to the more detailed syntax trees that are used in several natural-language processing techniques

A randomized trial of an intervention to improve use and adherence to effective coronary heart disease prevention strategies

<p>Abstract</p> <p>Background</p> <p>Efficacious strategies for the primary prevention of coronary heart disease (CHD) are underused, and, when used, have low adherence. Existing efforts to improve use and adherence to these efficacious strategies have been so intensive that they are impractical for clinical practice.</p> <p>Methods</p> <p>We conducted a randomized trial of a CHD prevention intervention (including a computerized decision aid and automated tailored adherence messages) at one university general internal medicine practice. After obtaining informed consent and collecting baseline data, we randomized patients (men and women age 40-79 with no prior history of cardiovascular disease) to either the intervention or usual care. We then saw them for two additional study visits over 3 months. For intervention participants, we administered the decision aid at the primary study visit (1 week after baseline visit) and then mailed 3 tailored adherence reminders at 2, 4, and 6 weeks. We assessed our outcomes (including the predicted likelihood of angina, myocardial infarction, and CHD death over 10 years (CHD risk) and self-reported adherence) between groups at 3 month follow-up. Data collection occurred from June 2007 through December 2009. All study procedures were IRB approved.</p> <p>Results</p> <p>We randomized 160 eligible patients (81 intervention; 79 control) and followed 96% to study conclusion. Mean predicted CHD risk at baseline was 11.3%. The intervention increased self-reported adherence to chosen risk reducing strategies by 25 percentage points (95% CI 8% to 42%), with the biggest effect for aspirin. It also changed predicted CHD risk by -1.1% (95% CI -0.16% to -2%), with a larger effect in a pre-specified subgroup of high risk patients.</p> <p>Conclusion</p> <p>A computerized intervention that involves patients in CHD decision making and supports adherence to effective prevention strategies can improve adherence and reduce predicted CHD risk.</p> <p>Clinical trials registration number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00494052">NCT00494052</a></p

Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes

<p>Abstract</p> <p>Background</p> <p>Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. <it>Momordica charantia </it>or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes.</p> <p>Methods</p> <p>Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR).</p> <p>Results</p> <p>Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol.</p> <p>Conclusion</p> <p>Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.</p

Packages of Care for Alcohol Use Disorders in Low- And Middle-Income Countries

In the fourth in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Vivek Benegal and colleagues discuss the treatment of alcohol use disorders