Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n ≈ 24 per dose per compound) were exposed to test compounds (0.4–120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system

Water-Use Data in the United States: Challenges and Future Directions

In the United States, greater attention has been given to developing water supplies and quantifying available waters than determining who uses water, how much they withdraw and consume, and how and where water use occurs. As water supplies are stressed due to an increasingly variable climate, changing land-use, and growing water needs, greater consideration of the demand side of the water balance equation is essential. Data about the spatial and temporal aspects of water use for different purposes are now critical to long-term water supply planning and resource management. We detail the current state of water-use data, the major stakeholders involved in their collection and applications, and the challenges in obtaining high-quality nationally consistent data applicable to a range of scales and purposes. Opportunities to improve access, use, and sharing of water-use data are outlined. We cast a vision for a world-class national water-use data product that is accessible, timely, and spatially detailed. Our vision will leverage the strengths of existing local, state, and federal agencies to facilitate rapid and informed decision-making, modeling, and science for water resources. To inform future decision-making regarding water supplies and uses, we must coordinate efforts to substantially improve our capacity to collect, model, and disseminate water-use data

HIV-1 protease inhibitors and clinical malaria: A secondary analysis of the AIDS Clinical Trials Group A5208 study

HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted. Copyrigh

Tracking of unpredictable moving stimuli by pigeons

Despite being observed throughout the animal kingdom, catching a moving object is a complex task and little is known about the mechanisms that underlie this behavior in non-human animals. Three experiments examined the role of prediction in capture of a moving object by pigeons. In Experiment 1, a stimulus moved in a linear trajectory, but sometimes made an unexpected 90o turn. The sudden turn had only a modest effect on capture and error location, and the analyses suggested that the birds had adjusted their tracking to the novel motion. In Experiment 2, the role of visual input during a turn was tested by inserting disappearances (either 1.5 cm or 4.5 cm) on both the straight and turn trials. The addition of the disappearance had little effect on capture success, but delayed capture location with the larger disappearance leading to greater delay. Error analyses indicated that the birds adapted to the post-turn, post-disappearance motion. Experiment 3 tested the role of visual input when the motion disappeared behind an occluder and emerged in either a straight line or at a 90o angle. The occluder produced a disruption in capture success but did not delay capture. Error analyses indicated that the birds did not adjust their tracking to the new motion on turn trials following occlusion. The combined results indicate that pigeons can anticipate the future position of a stimulus, and can adapt to sudden, unpredictable changes in motion but do so better after a disappearance than after an occlusion

The Frequency of Malaria Is Similar among Women Receiving either Lopinavir/Ritonavir or Nevirapine-based Antiretroviral Treatment

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population

SBML Level 3: an extensible format for the exchange and reuse of biological models

Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

Student public commitment in a school-based diabetes prevention project: impact on physical health and health behavior

<p>Abstract</p> <p>Background</p> <p>As concern about youth obesity continues to mount, there is increasing consideration of widespread policy changes to support improved nutritional and enhanced physical activity offerings in schools. A critical element in the success of such programs may be to involve students as spokespeople for the program. Making such a public commitment to healthy lifestyle program targets (improved nutrition and enhanced physical activity) may potentiate healthy behavior changes among such students and provide a model for their peers. This paper examines whether student's "public commitment"--voluntary participation as a peer communicator or in student-generated media opportunities--in a school-based intervention to prevent diabetes and reduce obesity predicted improved study outcomes including reduced obesity and improved health behaviors.</p> <p>Methods</p> <p>Secondary analysis of data from a 3-year randomized controlled trial conducted in 42 middle schools examining the impact of a multi-component school-based program on body mass index (BMI) and student health behaviors. A total of 4603 students were assessed at the beginning of sixth grade and the end of eighth grade. Process evaluation data were collected throughout the course of the intervention. All analyses were adjusted for students' baseline values. For this paper, the students in the schools randomized to receive the intervention were further divided into two groups: those who participated in public commitment activities and those who did not. Students from comparable schools randomized to the assessment condition constituted the control group.</p> <p>Results</p> <p>We found a lower percentage of obesity (greater than or equal to the 95^thpercentile for BMI) at the end of the study among the group participating in public commitment activities compared to the control group (21.5% vs. 26.6%, p = 0.02). The difference in obesity rates at the end of the study was even greater among the subgroup of students who were overweight or obese at baseline; 44.6% for the "public commitment" group, versus 53.2% for the control group (p = 0.01). There was no difference in obesity rates between the group not participating in public commitment activities and the control group (26.4% vs. 26.6%).</p> <p>Conclusions</p> <p>Participating in public commitment activities during the HEALTHY study may have potentiated the changes promoted by the behavioral, nutrition, and physical activity intervention components.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov number, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00458029">NCT00458029</a></p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists