PPARs and Anticancer Therapies

Editoria

Multiple steroid and thyroid hormones detected in baleen from eight whale species

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Conservation Physiology 5 (2017): cox061, doi:10.1093/conphys/cox061.Recent studies have demonstrated that some hormones are present in baleen powder from bowhead (Balaena mysticetus) and North Atlantic right (Eubalaena glacialis) whales. To test the potential generalizability of this technique for studies of stress and reproduction in large whales, we sought to determine whether all major classes of steroid and thyroid hormones are detectable in baleen, and whether these hormones are detectable in other mysticetes. Powdered baleen samples were recovered from single specimens of North Atlantic right, bowhead, blue (Balaenoptera [B.]musculus), sei (B. borealis), minke (B. acutorostrata), fin (B. physalus), humpback (Megaptera novaeangliae) and gray (Eschrichtius robustus) whales. Hormones were extracted with a methanol vortex method, after which we tested all species with commercial enzyme immunoassays (EIAs, Arbor Assays) for progesterone, testosterone, 17β-estradiol, cortisol, corticosterone, aldosterone, thyroxine and tri-iodothyronine, representing a wide array of steroid and thyroid hormones of interest for whale physiology research. In total, 64 parallelism tests (8 species × 8 hormones) were evaluated to verify good binding affinity of the assay antibodies to hormones in baleen. We also tested assay accuracy, although available sample volume limited this test to progesterone, testosterone and cortisol. All tested hormones were detectable in baleen powder of all species, and all assays passed parallelism and accuracy tests. Although only single individuals were tested, the consistent detectability of all hormones in all species indicates that baleen hormone analysis is likely applicable to a broad range of mysticetes, and that the EIA kits tested here perform well with baleen extract. Quantification of hormones in baleen may be a suitable technique with which to explore questions that have historically been difficult to address in large whales, including pregnancy and inter-calving interval, age of sexual maturation, timing and duration of seasonal reproductive cycles, adrenal physiology and metabolic rate.This work was supported by (1) the Center for Bioengineering Innovation at Northern Arizona University and (2) the New England Aquarium

Regional Climate Trends and Scenarios for the U.S. National Climate Assessment Part 4. Climate of the U.S. Great Plains

This document is one of series of regional climate descriptions designed to provide input that can be used in the development of the National Climate Assessment (NCA). As part of a sustained assessment approach, it is intended that these documents will be updated as new and well-vetted model results are available and as new climate scenario needs become clear. It is also hoped that these documents (and associated data and resources) are of direct benefit to decision makers and communities seeking to use this information in developing adaptation plans. There are nine reports in this series, one each for eight regions defined by the NCA, and one for the contiguous U.S. The eight NCA regions are the Northeast, Southeast, Midwest, Great Plains, Northwest, Southwest, Alaska, and Hawai‘i/Pacific Islands. These documents include a description of the observed historical climate conditions for each region and a set of climate scenarios as plausible futures – these components are described in more detail below. While the datasets and simulations in these regional climate documents are not, by themselves, new, (they have been previously published in various sources), these documents represent a more complete and targeted synthesis of historical and plausible future climate conditions around the specific regions of the NCA. There are two components of these descriptions. One component is a description of the historical climate conditions in the region. The other component is a description of the climate conditions associated with two future pathways of greenhouse gas emissions

Divergent HIV and Simian Immunodeficiency Virus Surveillance, Zaire

Recent HIV infection or divergent HIV or simian immunodeficiency virus (SIV) strains may be responsible for Western blot–indeterminate results on 70 serum samples from Zairian hospital employees that were reactive in an enzyme immunoassay. Using universal polymerase chain reaction HIV-1, HIV-2, and SIV primers, we detected 1 (1.4%) HIV-1 sequence. Except for 1 sample, no molecular evidence for unusual HIV- or SIV-like strains in this sampling was found

Transporting Clinical Research to Community Settings: Designing and Conducting a Multisite Trial of Brief Strategic Family Therapy

This paper describes the development and implementation of a trial of Brief Strategic Family Therapy (BSFT), an evidence-based drug intervention for adolescents, in eight community substance abuse treatment programs. Researchers and treatment programs collaborated closely to identify and overcome challenges, many of them related to achieving results that were both scientifically rigorous and applicable to the widest possible variety of adolescent substance abuse treatment programs. To meet these challenges, the collaborative team drew on lessons and practices from efficacy, effectiveness, and implementation research

Implementing Provider‐based Sampling for the National Children's Study: Opportunities and Challenges

Background:  The National Children's Study (NCS) was established as a national probability sample of births to prospectively study children's health starting from in utero to age 21. The primary sampling unit was 105 study locations (typically a county). The secondary sampling unit was the geographic unit (segment), but this was subsequently perceived to be an inefficient strategy. Methods and Results:  This paper proposes that second‐stage sampling using prenatal care providers is an efficient and cost‐effective method for deriving a national probability sample of births in the US. It offers a rationale for provider‐based sampling and discusses a number of strategies for assembling a sampling frame of providers. Also presented are special challenges to provider‐based sampling pregnancies, including optimising key sample parameters, retaining geographic diversity, determining the types of providers to include in the sample frame, recruiting women who do not receive prenatal care, and using community engagement to enrol women. There will also be substantial operational challenges to sampling provider groups. Conclusion:  We argue that probability sampling is mandatory to capture the full variation in exposure and outcomes expected in a national cohort study, to provide valid and generalisable risk estimates, and to accurately estimate policy (such as screening) benefits from associations reported in the NCS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94504/1/ppe12005.pd

Risk‐Treatment Paradox in the Selection of Transradial Access for Percutaneous Coronary Intervention

Background: Access site complications contribute to morbidity and mortality during percutaneous coronary intervention (PCI). Transradial arterial access significantly lowers the risk of access site complications compared to transfemoral arteriotomy. We sought to develop a prediction model for access site complications in patients undergoing PCI with femoral arteriotomy, and assess whether transradial access was selectively used in patients at high risk for complications. Methods and Results: We analyzed 17 509 patients who underwent PCI without circulatory support from 2008 to 2011 at 5 institutions. Transradial arterial access was used in 17.8% of patients. In those who underwent transfemoral access, 177 (1.2%) patients had access site complications. Using preprocedural clinical and demographic data, a prediction model for femoral arteriotomy complications was generated. The variables retained in the model included: elevated age (P<0.001), female gender (P<0.001), elevated troponin (P<0.001), decreased renal function or dialysis (P=0.002), emergent PCI (P=0.01), prior PCI (P=0.005), diabetes (P=0.008), and peripheral artery disease (P=0.003). The model showed moderate discrimination (optimism‐adjusted c‐statistic=0.72) and was internally validated via bootstrap resampling. Patients with higher predicted risk of complications via transfemoral access were less likely to receive transradial access (P<0.001). Similar results were seen in patients presenting with and without ST‐segment myocardial infarction and when adjusting for individual physician operator. Conclusions: We generated and validated a model for transfemoral access site complications during PCI. Paradoxically, patients most likely to develop access site complications from transfemoral access, and therefore benefit from transradial access, were the least likely to receive transradial access

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing(1,2). Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q - the inheritance of both copies of this material from one parent - and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders(3,4), revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo ( that is, newly arisen and not inherited) single-base substitution, G608G( GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62684/1/nature01629.pd

Multiple steroid and thyroid hormones detected in baleen from eight whale species

Recent studies have demonstrated that some hormones are present in baleen powder from bowhead (Balaena mysticetus) and North Atlantic right (Eubalaena glacialis) whales. To test the potential generalizability of this technique for studies of stress and reproduction in large whales, we sought to determine whether all major classes of steroid and thyroid hormones are detectable in baleen, and whether these hormones are detectable in other mysticetes. Powdered baleen samples were recovered from single specimens of North Atlantic right, bowhead, blue (Balaenoptera [B.]musculus), sei (B. borealis), minke (B. acutorostrata), fin (B. physalus), humpback (Megaptera novaeangliae) and gray (Eschrichtius robustus) whales. Hormones were extracted with a methanol vortex method, after which we tested all species with commercial enzyme immunoassays (EIAs, Arbor Assays) for progesterone, testosterone, 17β-estradiol, cortisol, corticosterone, aldosterone, thyroxine and tri-iodothyronine, representing a wide array of steroid and thyroid hormones of interest for whale physiology research. In total, 64 parallelism tests (8 species × 8 hormones) were evaluated to verify good binding affinity of the assay antibodies to hormones in baleen. We also tested assay accuracy, although available sample volume limited this test to progesterone, testosterone and cortisol. All tested hormones were detectable in baleen powder of all species, and all assays passed parallelism and accuracy tests. Although only single individuals were tested, the consistent detectability of all hormones in all species indicates that baleen hormone analysis is likely applicable to a broad range of mysticetes, and that the EIA kits tested here perform well with baleen extract. Quantification of hormones in baleen may be a suitable technique with which to explore questions that have historically been difficult to address in large whales, including pregnancy and inter-calving interval, age of sexual maturation, timing and duration of seasonal reproductive cycles, adrenal physiology and metabolic rate