Summer and Winter Spatial Habitat Use by the Lake Erie Watersnake

In an effort to provide information to guide habitat management for the Lake Erie watersnake Nerodia sipedon insularum, a federally threatened and Ohio state endangered species, we used radiotelemetry to obtain spatial habitat data for adult snakes during the summer active season and during winter hibernation. During the summer active season, terrestrial habitat use was limited to a narrow band of shoreline. Among individuals, maximum distance inland from shore ranged from 1 to 50 m (mean = 8 m) and linear extent of shoreline ranged from 30 to 1,360 m (mean = 261 m). Winter hibernation occurred at varying distances inland with individual hibernation sites ranging from 1 to 580 m (mean = 29 m) from shore. Habitat use did not differ between males and females. Existing U.S. Fish and Wildlife Service habitat management guidelines suggest that ground-disturbing activities within potential hibernation areas (defined as terrestrial habitat within 161 m of shore) should be avoided in winter to prevent harm to hibernating snakes. They suggest further that excavation and removal of shrubs, standing or downed trees, root masses, animal burrows, piled rocks, cliffs, or bedrock within 21 m of shore should be avoided in summer to prevent harm to active snakes. Given that Lake Erie watersnakes have recovered to the point where delisting is being proposed, these habitat guidelines appear to be sufficient. However, maintaining voluntary compliance with habitat guidelines and meeting the need for continued public outreach will be vital to ensure long-term persistence

Mid-infrared Selection of Active Galactic Nuclei with the Wide-Field Infrared Survey Explorer. I. Characterizing WISE-selected Active Galactic Nuclei in COSMOS

The Wide-field Infrared Survey Explorer (WISE) is an extremely capable and efficient black hole finder. We present a simple mid-infrared color criterion, W1 – W2 ≥ 0.8 (i.e., [3.4]–[4.6] ≥0.8, Vega), which identifies 61.9 ± 5.4 active galactic nucleus (AGN) candidates per deg^2 to a depth of W2 ~ 15.0. This implies a much larger census of luminous AGNs than found by typical wide-area surveys, attributable to the fact that mid-infrared selection identifies both unobscured (type 1) and obscured (type 2) AGNs. Optical and soft X-ray surveys alone are highly biased toward only unobscured AGNs, while this simple WISE selection likely identifies even heavily obscured, Compton-thick AGNs. Using deep, public data in the COSMOS field, we explore the properties of WISE-selected AGN candidates. At the mid-infrared depth considered, 160 μJy at 4.6 μm, this simple criterion identifies 78% of Spitzer mid-infrared AGN candidates according to the criteria of Stern et al. and the reliability is 95%. We explore the demographics, multiwavelength properties and redshift distribution of WISE-selected AGN candidates in the COSMOS field

Deletion of the Basement Membrane Heparan Sulfate Proteoglycan Type XVIII Collagen Causes Hypertriglyceridemia in Mice and Humans

Background: Lipoprotein lipase (Lpl) acts on triglyceride-rich lipoproteins in the peripheral circulation, liberating free fatty acids for energy metabolism or storage. This essential enzyme is synthesized in parenchymal cells of adipose tissue, heart, and skeletal muscle and migrates to the luminal side of the vascular endothelium where it acts upon circulating lipoproteins. Prior studies suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the endothelium, but genetically altering endothelial cell heparan sulfate had no effect on Lpl localization or lipolysis. The objective of this study was to determine if extracellular matrix proteoglycans affect Lpl distribution and triglyceride metabolism. Methods and Findings: We examined mutant mice defective in collagen XVIII (Col18), a heparan sulfate proteoglycan present in vascular basement membranes. Loss of Col18 reduces plasma levels of Lpl enzyme and activity, which results in mild fasting hypertriglyceridemia and diet-induced hyperchylomicronemia. Humans with Knobloch Syndrome caused by a null mutation in the vascular form of Col18 also present lower than normal plasma Lpl mass and activity and exhibit fasting hypertriglyceridemia. Conclusions: This is the first report demonstrating that Lpl presentation on the lumenal side of the endothelium depends on a basement membrane proteoglycan and demonstrates a previously unrecognized phenotype in patients lacking Col18.National Institute of Health (NIH)[HL087228]National Institute of Health (NIH)[GM33063]National Institute of Health (NIH)[HL67255]CEPID/FAPESPCNPqUniversity of Colorado Denver Department of MedicineLeducq FoundationAmerican Heart Association[0735038N

WISE Discovery of Low Metallicity Blue Compact Dwarf Galaxies

We report two new low metallicity blue compact dwarf galaxies (BCDs), WISEP J080103.93+264053.9 (hereafter W0801+26) and WISEP J170233.53+180306.4 (hereafter W1702+18), discovered using the Wide-field Infrared Survey Explorer (WISE). We identified these two BCDs from their extremely red colors at mid-infrared wavelengths, and obtained follow-up optical spectroscopy using the Low Resolution Imaging Spectrometer on Keck I. The mid-infrared properties of these two sources are similar to the well studied, extremely low metallicity galaxy SBS 0335-052E. We determine metallicities of 12 + log(O/H) = 7.75 and 7.63 for W0801+26 and W1702+18, respectively, placing them amongst a very small group of very metal deficient galaxies (Z 300 Angstrom Hbeta equivalent widths, similar to SBS 0335-052E, imply the existence of young (< 5 Myr) star forming regions. We measure star formation rates of 2.6 and 10.9 Msun/yr for W0801+26 and W1702+18, respectively. These BCDs, showing recent star formation activity in extremely low metallicity environments, provide new laboratories for studying star formation in extreme conditions and are low-redshift analogs of the first generation of galaxies to form in the universe. Using the all-sky WISE survey, we discuss a new method to identify similar star forming, low metallicity BCDs.Comment: Accepted for publication in ApJ

Exercise training induces depot-specific adaptations to white and brown adipose tissue

Exercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise11425439This work was supported by National Institutes of Health grants R01-HL138738 and K01-DK105109 (to K.I.S.), R01-DK099511 (to L.J.G.), and 5P30 DK36836 (Joslin Diabetes Center DRC). The authors thank Nathan Makarewicz for editorial contribution

The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue

Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia1,2. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism3–5. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as ‘lipokines’6–8. Because BAT is a specialized metabolic tissue that takes up and burns lipids and is linked to systemic metabolic homeostasis, we hypothesized that there might be thermogenic lipokines that activate BAT in response to cold. Here we show that the lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a stimulator of BAT activity, and that its levels are negatively correlated with body-mass index and insulin sensitivity. Using a global lipidomic analysis, we found that 12,13-diHOME was increased in the circulation of humans and mice exposed to cold. Furthermore, we found that the enzymes that produce 12,13-diHOME were uniquely induced in BAT by cold stimulation. The injection of 12,13-diHOME acutely activated BAT fuel uptake and enhanced cold tolerance, which resulted in decreased levels of serum triglycerides. Mechanistically, 12,13-diHOME increased fatty acid (FA) uptake into brown adipocytes by promoting the translocation of the FA transporters FATP1 and CD36 to the cell membrane. These data suggest that 12,13-diHOME, or a functional analog, could be developed as a treatment for metabolic disorders

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe