ATP Binding Cassette Sub-family Member 2 (ABCG2) and Xenobiotic Exposure During Early Mouse Embryonic Stem Cell Differentiation

Background: ATP binding cassette sub-family member 2 (ABCG2) is a welldefined efflux transporter found in a variety of tissues. The role of ABCG2 during early embryonic development, however, is not established. Previous work which compared data from the ToxCast screening program with that from in-house studies suggested an association exists between exposure to xenobiotics that regulate Abcg2 transcription and differentiation of mouse embryonic stem cells (mESC), a relationship potentially related to redox homeostasis. Methods: mESC were grown for up to 9 days. Pharmacological inhibitors were used to assess transporter function with and without xenobiotic exposure. Proliferation and differentiation were evaluated using RedDot1 and quantiative reverse transcriptase-polymerase chain reaction, respectively. ABCG2 activity was assessed using a Pheophorbide a-based fluorescent assay. Protein expression was measured by capillary-based immunoassay. Results: ABCG2 activity increased in differentiating mESC. Treatment with K0143, an inhibitor of ABCG2, had no effect on proliferation or differentiation. As expected, mitoxantrone and topotecan, two chemotherapeutics, displayed increased toxicity in the presence of K0143. Exposure to K0143 in combination with chemicals predicted by ToxCast to regulate ABCG2 expression did not alter xenobiotic-induced toxicity. Moreover, inhibition of ABCG2 did not shift the toxicity of either tert-Butyl hydroperoxide or paraquat, two oxidative stressors. Conclusion: As previously reported, ABCG2 serves a protective role in mESC. The role of ABCG2 in regulating redox status, however, was unclear. The hypothesis that ABCG2 plays a fundamental role during mESC differentiation or that regulation of the receptor by xenobiotics may be associated with altered mESC differentiation could not be supported

NMFS / Interagency Working Group Evaluation of CITES Criteria and Guidelines.

EXECUTIVE SUMMARY: At present, the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) criteria used to assess whether a population qualifies for inclusion in the CITES Appendices relate to (A) size of the population, (B) area of distribution of the population, and (C) declines in the size of the population. Numeric guidelines are provided as indicators of a small population (less than 5,000 individuals), a small subpopulation (less than 500 individuals), a restricted area of distribution for a population (less than 10,000 km2), a restricted area of distribution for a subpopula-tion (less than 500 km2), a high rate of decline (a decrease of 50% or more in total within 5 years or two generations whichever is longer or, for a small wild population, a decline of 20% or more in total within ten years or three generations whichever is longer), large fluctuations (population size or area of distribution varies widely, rapidly and frequently, with a variation greater than one order of magnitude), and a short-term fluctuation (one of two years or less). The Working Group discussed several broad issues of relevance to the CITES criteria and guidelines. These included the importance of the historical extent of decline versus the recent rate of decline; the utility and validity of incorporating relative population productivity into decline criteria; the utility of absolute numbers for defining small populations or small areas; the appropriateness of generation times as time frames for examining declines; the importance of the magnitude and frequency of fluctuations as factors affecting risk of extinction; and the overall utility of numeric thresh-olds or guidelines

Genome-Wide Association Study of Tanning Phenotype in a Population of European Ancestry

We conducted a multistage genome-wide association study (GWAS) of tanning response after exposure to sunlight in over 9,000 men and women of European ancestry who live in the United States. An initial analysis of 528,173 single-nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified LOC401937 (rs966321) on chromosome 1 as a novel locus highly associated with tanning ability, and we confirmed this association in 870 women controls from a skin cancer case–control study with joint P-value=1.6 × 10−9. We further genotyped this SNP in two subsequent replication studies (one with 3,750 women and the other with 2,405 men). This association was not replicated in either of these two studies. We found that several SNPs reaching the genome-wide significance level are located in or adjacent to the loci previously known as pigmentation genes: MATP, IRF4, TYR, OCA2, and MC1R. Overall, these tanning ability–related loci are similar to the hair color–related loci previously reported in the GWAS of hair color

Validation of Kepler's Multiple Planet Candidates. III: Light Curve Analysis & Announcement of Hundreds of New Multi-planet Systems

The Kepler mission has discovered over 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of them in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false-positives indicates that the multiplanet systems contain very few false-positive signals due to other systems not gravitationally bound to the target star (Lissauer, J. J., et al., 2012, ApJ 750, 131). False positives in the multi- planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false-positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ~2 unidentified false-positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves and ground-based spectroscopy and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. None the less, our result nearly doubles the number of verified exoplanets.Comment: 138 pages, 8 Figures, 5 Tables. Accepted for publications in the Astrophysical Journa

Instrument development, data collection, and characteristics of practices, staff, and measures in the Improving Quality of Care in Diabetes (iQuaD) Study

Peer reviewedPublisher PD

What matters to program partners when implementing a community-based exercise program for people post-stroke? A theory-based qualitative study and cost analysis

BackgroundCommunity-based exercise programs integrating a healthcare-community partnership (CBEP-HCP) can facilitate lifelong exercise participation for people post-stroke. Understanding the process of implementation from multiple perspectives can inform strategies to promote program sustainability.PurposeTo explore stakeholders' experiences with undertaking first-time implementation of a group, task-oriented CBEP-HCP for people post-stroke and describe associated personnel and travel costs.MethodsWe conducted a descriptive qualitative study within a pilot randomized controlled trial. In three cities, trained fitness instructors delivered a 12-week CBEP-HCP targeting balance and mobility limitations to people post-stroke at a recreation centre with support from a healthcare partner. Healthcare and recreation managers and personnel at each site participated in semi-structured interviews or focus groups by telephone post-intervention. Interviews and data analysis were guided by the Consolidated Framework of Implementation Research and Theoretical Domains Framework, for managers and program providers, respectively. We estimated personnel and travel costs associated with implementing the program.ResultsTwenty individuals from three sites (4 recreation and 3 healthcare managers, 7 fitness instructors, 3 healthcare partners, and 3 volunteers) participated. We identified two themes related to the decision to partner and implement the program: (1) Program quality and packaging, and cost-benefit comparisons influenced managers' decisions to partner and implement the CBEP-HCP, and (2) Previous experiences and beliefs about program benefits influenced staff decisions to become instructors. We identified two additional themes related to experiences with training and program delivery: (1) Program staff with previous experience and training faced initial role-based challenges that resolved with program delivery, and (2) Organizational capacity to manage program resource requirements influenced managers' decisions to continue the program. Participants identified recommendations related to partnership formation, staff/volunteer selection, training, and delivery of program activities. Costs (in CAD) for first-time program implementation were: healthcare partner ($680); fitness coordinators and instructors ($3,153); and participant transportation (personal vehicle: $283; public transit:$110).ConclusionDuring first-time implementation of a CBEP-HCP, healthcare and hospital managers focused on cost, resource requirements, and the added-value of the program, while instructors and healthcare partners focused on their preparedness for the role and their ability to manage individuals with balance and mobility limitations. Trial Registration: ClinicalTrials.gov, NCT03122626. Registered April 17, 2017—Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT0312262

Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak

TOC Summary Line: Healthcare workers in hospitals affected by SARS experience increased psychological stress 1–2 years after the outbreak