Isolation of an antimicrobial compound produced by bacteria associated with reef-building corals

� 2016 Raina et al. Bacterial communities associated with healthy corals produce antimicrobial compounds that inhibit the colonization and growth of invasive microbes and potential pathogens. To date, however, bacteria-derived antimicrobial molecules have not been identified in reef-building corals. Here, we report the isolation of an antimicrobial compound produced by Pseudovibrio sp. P12, a common and abundant coral-associated bacterium. This strain was capable of metabolizing dimethylsulfoniopropionate (DMSP), a sulfur molecule produced in high concentrations by reef-building corals and playing a role in structuring their bacterial communities. Bioassay-guided fractionation coupled with nuclear magnetic resonance (NMR) and mass spectrometry (MS), identified the antimicrobial as tropodithietic acid (TDA), a sulfur-containing compound likely derived from DMSP catabolism. TDA was produced in large quantities by Pseudovibrio sp., and prevented the growth of two previously identified coral pathogens, Vibrio coralliilyticus and V. owensii, at very low concentrations (0.5 μg/mL) in agar diffusion assays. Genome sequencing of Pseudovibrio sp. P12 identified gene homologs likely involved in the metabolism of DMSP and production of TDA. These results provide additional evidence for the integral role of DMSP in structuring coral-associated bacterial communities and underline the potential of these DMSP-metabolizing microbes to contribute to coral disease prevention

Genetic markers for antioxidant capacity in a reef-building coral

© 2016 The Authors. The current lack of understanding of the genetic basis underlying environmental stress tolerance in reef-building corals impairs the development of new management approaches to confronting the global demise of coral reefs. On the Great Barrier Reef (GBR), an approximately 51% decline in coral cover occurred over the period 1985-2012. We conducted a gene-by-environment association analysis across 12 latitude on the GBR, as well as both in situ and laboratory genotype-by-phenotype association analyses. These analyses allowed us to identify alleles at two genetic loci that account for differences in environmental stress tolerance and antioxidant capacity in the common coral Acropora millepora. The effect size for antioxidant capacity was considerable and biologically relevant (32.5 and 14.6% for the two loci). Antioxidant capacity is a critical component of stress tolerance because a multitude of environmental stressors cause increased cellular levels of reactive oxygen species. Our findings provide the first step toward the development of novel coral reef management approaches, such as spatial mapping of stress tolerance for use in marine protected area design, identification of stress-tolerant colonies for assisted migration, and marker-assisted selective breeding to create more tolerant genotypes for restoration of denuded reefs

Correlating Agricultural Use of Organophosphates with Outdoor Air Concentrations: A Particular Concern for Children

For the organophosphate pesticide chlorpyrifos, median inhalation noncancer, acute children’s exposures in agricultural communities are elevated above reference doses; for diazinon, similar exposures are nearly elevated. We used multivariate linear regression analysis to examine the temporal and spatial associations between agricultural use and measured air concentrations of chlorpyrifos, chlorpyrifos oxon, diazinon, and malathion. Agricultural use within a 3-mile radius on the monitoring day and use on the 2–4 prior days were significantly associated with air concentrations (p < 0.01) for all analytes except malathion; chlorpyrifos oxon showed the strongest association (p < 0.0001). In the final models, which included weather parameters, the proportion of variance (r (2), adjusted for the number of model variables) for all analytes ranged from 0.28 (p < 0.01) for malathion to 0.65 (p < 0.0001) for diazinon. Recent cellular, animal, and human evidence of toxicity, particularly in newborns, supports the public health concern indicated by initial risk estimates. Agricultural applications of organophosphates and their oxon products may have substantial volatization and off-field movement and are a probable source of exposures of public health concern

Far Ultraviolet Spectroscopic Explorer Spectroscopy of the O VI Resonance Doublet in Sand 2 (WO)

We present Far Ultraviolet Spectroscopic Explorer spectroscopy of Sand 2, an LMC WO-type Wolf-Rayet star, revealing the O VI resonance P Cygni doublet at 1032-1038 Å. These data are combined with Hubble Space Telescope Faint Object Spectrograph ultraviolet and Mount Stromlo 2.3 m optical spectroscopy and analyzed using a spherical, non-LTE, line-blanketed code. Our study reveals exceptional stellar parameters: T* ~ 150,000 K, v∞ = 4100 km s-1, log(L/L☉) = 5.3, andimg1.gif = 1 × 10-5 M☉ yr-1, if we adopt a volume filling factor of 10%. Elemental abundances of C/He ~ 0.7 ± 0.2 and O/He ~ 0.15img2.gif by number qualitatively support previous recombination line studies. We confirm that Sand 2 is more chemically enriched in carbon than LMC WC stars and that it is expected to undergo a supernova explosion within the next 5 × 104 yr

The assessment of the quality of reporting of meta-analyses in diagnostic research: a systematic review

<p>Abstract</p> <p>Background</p> <p>Over the last decade there have been a number of guidelines published, aimed at improving the quality of reporting in published studies and reviews. In systematic reviews this may be measured by their compliance with the PRISMA statement. This review aims to evaluate the quality of reporting in published meta-analyses of diagnostic tests, using the PRISMA statement and establish whether there has been a measurable improvement over time.</p> <p>Methods</p> <p>Eight databases were searched for reviews published prior to 31^stDecember 2008. Studies were selected if they evaluated a diagnostic test, measured performance, searched two or more databases, stated the search terms and inclusion criteria, and used a statistical method to summarise a test's performance. Data were extracted on the review characteristics and items of the PRISMA statement. To measure the change in the quality of reporting over time, PRISMA items for two periods of equal duration were compared.</p> <p>Results</p> <p>Compliance with the PRISMA statement was generally poor: none of the reviews completely adhered to all 27 checklist items. Of the 236 meta-analyses included following selection: only 2(1%) reported the study protocol; 59(25%) reported the searches used; 76(32%) reported the results of a risk of bias assessment; and 82(35%) reported the abstract as a structured summary. Only 11 studies were published before 2000. Thus, the impact of QUOROM on the quality of reporting was not evaluated. However, the periods 2001-2004 and 2005-2008 (covering 93% of studies) were compared using relative risks (RR). There was an increase in the proportion of reviews reporting on five PRISMA items: eligibility criteria (RR 1.13, 95% CI 1.00 - 1.27); risk of bias across studies (methods) (RR 1.81, 95% CI 1.34 - 2.44); study selection results (RR 1.48, 95% CI 1.05 - 2.09); results of individual studies (RR 1.37, 95% CI 1.09 - 1.72); risk of bias across studies (results) (RR 1.65, 95% CI 1.20 - 2.25).</p> <p>Conclusion</p> <p>Although there has been an improvement in the quality of meta-analyses in diagnostic research, there are still many deficiencies in the reporting which future reviewers need to address if readers are to trust the validity of the reported findings.</p

Cognitive interviewing methodology in the development of a pediatric item bank: a patient reported outcomes measurement information system (PROMIS) study

<p>Abstract</p> <p>Background</p> <p>The evaluation of patient-reported outcomes (PROs) in health care has seen greater use in recent years, and methods to improve the reliability and validity of PRO instruments are advancing. This paper discusses the cognitive interviewing procedures employed by the Patient Reported Outcomes Measurement Information System (PROMIS) pediatrics group for the purpose of developing a dynamic, electronic item bank for field testing with children and adolescents using novel computer technology. The primary objective of this study was to conduct cognitive interviews with children and adolescents to gain feedback on items measuring physical functioning, emotional health, social health, fatigue, pain, and asthma-specific symptoms.</p> <p>Methods</p> <p>A total of 88 cognitive interviews were conducted with 77 children and adolescents across two sites on 318 items. From this initial item bank, 25 items were deleted and 35 were revised and underwent a second round of cognitive interviews. A total of 293 items were retained for field testing.</p> <p>Results</p> <p>Children as young as 8 years of age were able to comprehend the majority of items, response options, directions, recall period, and identify problems with language that was difficult for them to understand. Cognitive interviews indicated issues with item comprehension on several items which led to alternative wording for these items.</p> <p>Conclusion</p> <p>Children ages 8–17 years were able to comprehend most item stems and response options in the present study. Field testing with the resulting items and response options is presently being conducted as part of the PROMIS Pediatric Item Bank development process.</p

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection

Abstract: Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells. Author Summary: A variety of physiological death signals, as well as pathological insults, trigger apoptosis, a genetically programmed form of cell death. Pathogens often induce host cell apoptosis to establish a successful infection. Neisseria gonorrhoeae (Ngo), the etiological agent of the sexually transmitted disease gonorrhoea, is a highly adapted obligate human-specific pathogen and has been shown to induce apoptosis in infected cells. Here we unveil the molecular mechanisms leading to apoptosis of infected cells. We show that Ngo-mediated apoptosis requires a special subset of proapoptotic proteins from the group of BH3-only proteins. BH3-only proteins act as stress sensors to translate toxic environmental signals to the initiation of apoptosis. In a siRNA-based miniscreen, we found Bim and Bmf, BH3-only proteins associated with the cytoskeleton, necessary to induce host cell apoptosis upon infection. Bim and Bmf inactivated different inhibitors of apoptosis and thereby induced cell death in response to infection. Our data unveil a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic cell death

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Cognitive interviewing methodology in the development of a pediatric item bank: a patient reported outcomes measurement information system (PROMIS) study

<p>Abstract</p> <p>Background</p> <p>The evaluation of patient-reported outcomes (PROs) in health care has seen greater use in recent years, and methods to improve the reliability and validity of PRO instruments are advancing. This paper discusses the cognitive interviewing procedures employed by the Patient Reported Outcomes Measurement Information System (PROMIS) pediatrics group for the purpose of developing a dynamic, electronic item bank for field testing with children and adolescents using novel computer technology. The primary objective of this study was to conduct cognitive interviews with children and adolescents to gain feedback on items measuring physical functioning, emotional health, social health, fatigue, pain, and asthma-specific symptoms.</p> <p>Methods</p> <p>A total of 88 cognitive interviews were conducted with 77 children and adolescents across two sites on 318 items. From this initial item bank, 25 items were deleted and 35 were revised and underwent a second round of cognitive interviews. A total of 293 items were retained for field testing.</p> <p>Results</p> <p>Children as young as 8 years of age were able to comprehend the majority of items, response options, directions, recall period, and identify problems with language that was difficult for them to understand. Cognitive interviews indicated issues with item comprehension on several items which led to alternative wording for these items.</p> <p>Conclusion</p> <p>Children ages 8–17 years were able to comprehend most item stems and response options in the present study. Field testing with the resulting items and response options is presently being conducted as part of the PROMIS Pediatric Item Bank development process.</p

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program