The Glucose Transporter GLUT4 and the Aminopeptidase vp165 Colocalise in Tubulo-Vesicular Elements in Adipocytes and Cardiomyocytes

The aminopeptidase vp165 is one of the major polypeptides enriched in GLUT4-containing vesicles immuno-isolated from adipocytes. In the present study we have confirmed and quantified the high degree of colocalisation between GLUT4 and vp165 using double label immuno-electron microscopy on vesicles isolated from adipocytes and heart. The percentage of vp165-containing vesicles that also contained GLUT4 was 91%, 76%, and 86% in rat adipocytes, 3T3-L1 adipocytes, and rat heart, respectively. Internalisation of a transferrin/HRP (Tf/HRP) conjugate by 3T3-L1 adipocytes, followed by diaminobenzidine treatment in intact cells, resulted in ablation of only 41% and 45% of GLUT4 and vp165, respectively, whereas endosomal markers are almost quantitatively ablated. Using immuno-electron microscopy on cryosections it was determined that in atrial cardiomyocytes GLUT4 and vp165 colocalised in a population of tubulo-vesicular (T-V) elements that were often found close to the plasma membrane. Double label immunocytochemistry indicated a high degree of overlap in these T-V elements between GLUT4 and vp165. However, in atrial cardiomyocytes a large proportion of GLUT4 was also present in secretory granules containing atrial natriuretic factor (ANF). In contrast, very little vp165 was detected in ANF granules. These data indicate that GLUT4 and vp165 are colocalised in an intracellular, post-endocytic, tubulo-vesicular compartment in adipocytes and cardiomyocytes suggesting that both proteins are sorted in a similar manner in these cells. However, GLUT4 but not vp165 is additionally localised in the regulated secretory pathway in atrial cardiomyocytes

2MASSJ035523.51+113337.4: A Young, Dusty, Nearby, Isolated Brown Dwarf Resembling A Giant Exoplanet

We present parallax and proper motion measurements, near-infrared spectra, and WISE photometry for the low surface gravity L5gamma dwarf 2MASSJ035523.37+113343.7 (2M0355). We use these data to evaluate photometric, spectral, and kinematic signatures of youth as 2M0355 is the reddest isolated L dwarf yet classified. We confirm its low-gravity spectral morphology and find a strong resemblance to the sharp triangular shaped $H$-band spectrum of the 10 Myr planetary-mass object 2M1207b. We find that 2M0355 is underluminous compared to a normal field L5 dwarf in the optical and MKO J,H, and K bands and transitions to being overluminous from 3-12 microns, indicating that enhanced photospheric dust shifts flux to longer wavelengths for young, low-gravity objects, creating a red spectral energy distribution. Investigating the near-infrared color magnitude diagram for brown dwarfs confirms that 2M0355 is redder and underluminous compared to the known brown dwarf population, similar to the peculiarities of directly imaged exoplanets 2M1207b and HR8799bcd. We calculate UVW space velocities and find that the motion of 2M0355 is consistent with young disk objects (< 2-3 Gyr) and it shows a high likelihood of membership in the AB Doradus association.Comment: 23 pages, 10 figures, 5 Tables, Submitted to AJ 13 May 201

Endogenous Avian Leukosis Virus subgroup E elements of the chicken reference genome

The chicken reference genome contains two endogenous Avian Leukosis Virus subgroup E (ALVE) insertions, but gaps and unresolved repetitive sequences in previous assemblies has hindered their precise characterisation. Detailed analysis of the most recent reference genome (GRCg6a) now shows both ALVEs within contiguous chromosome assemblies for the first time. ALVE6 (ALVE-JFevA) and ALVE-JFevB are both located on chromosome 1, with ALVE6 close to the p arm telomere. ALVE-JFevB is a structurally intact element containing the ALVE gag, pol and env genes, and is capable of forming replication competent viruses. In contrast, ALVE6 (ALVE-JFevA) contains a 3352 bp 5’ truncation and lacks the entire 5’ LTR and gag gene. Despite this, ALVE6 remains able to produce intact envelope protein, likely due to a mutation in the recognition site for a known inhibitory miRNA (miR-155). Whole genome resequencing datasets from layers, broilers and three independent sources of wild-caught red junglefowl were surveyed for the presence of each of these reference genome ALVEs. ALVE-JFevB was found in no other chicken or red junglefowl genomes, whereas ALVE6 was identified in some layers, broilers and native breeds, but not within any other red junglefowl genome. Improved assembly contiguity has facilitated better characterisation of the two ALVEs of the chicken reference genome. However, both the limited ALVE content and unique presence of ALVE-JFevB suggests that the reference individual is unrepresentative of ancestral Gallus gallus ALVE diversity

Examination of the association of sex and race/ethnicity with appearance concerns: A Scleroderma Patient-centered Intervention Network (SPIN) cohort study

Objective: Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. Methods: SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. Results: Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95,

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Davis, G. E., Baumgartner, M. F., Corkeron, P. J., Bell, J., Berchok, C., Bonnell, J. M., Thornton, J. B., Brault, S., Buchanan, G. A., Cholewiak, D. M., Clark, C. W., Delarue, J., Hatch, L. T., Klinck, H., Kraus, S. D., Martin, B., Mellinger, D. K., Moors-Murphy, H., Nieukirk, S., Nowacek, D. P., Parks, S. E., Parry, D., Pegg, N., Read, A. J., Rice, A. N., Risch, D., Scott, A., Soldevilla, M. S., Stafford, K. M., Stanistreet, J. E., Summers, E., Todd, S., & Van Parijs, S. M. Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data. Global Change Biology, (2020): 1-30, doi:10.1111/gcb.15191.Six baleen whale species are found in the temperate western North Atlantic Ocean, with limited information existing on the distribution and movement patterns for most. There is mounting evidence of distributional shifts in many species, including marine mammals, likely because of climate‐driven changes in ocean temperature and circulation. Previous acoustic studies examined the occurrence of minke (Balaenoptera acutorostrata ) and North Atlantic right whales (NARW; Eubalaena glacialis ). This study assesses the acoustic presence of humpback (Megaptera novaeangliae ), sei (B. borealis ), fin (B. physalus ), and blue whales (B. musculus ) over a decade, based on daily detections of their vocalizations. Data collected from 2004 to 2014 on 281 bottom‐mounted recorders, totaling 35,033 days, were processed using automated detection software and screened for each species' presence. A published study on NARW acoustics revealed significant changes in occurrence patterns between the periods of 2004–2010 and 2011–2014; therefore, these same time periods were examined here. All four species were present from the Southeast United States to Greenland; humpback whales were also present in the Caribbean. All species occurred throughout all regions in the winter, suggesting that baleen whales are widely distributed during these months. Each of the species showed significant changes in acoustic occurrence after 2010. Similar to NARWs, sei whales had higher acoustic occurrence in mid‐Atlantic regions after 2010. Fin, blue, and sei whales were more frequently detected in the northern latitudes of the study area after 2010. Despite this general northward shift, all four species were detected less on the Scotian Shelf area after 2010, matching documented shifts in prey availability in this region. A decade of acoustic observations have shown important distributional changes over the range of baleen whales, mirroring known climatic shifts and identifying new habitats that will require further protection from anthropogenic threats like fixed fishing gear, shipping, and noise pollution.We thank Chris Pelkie, David Wiley, Michael Thompson, Chris Tessaglia‐Hymes, Eric Matzen, Chris Tremblay, Lance Garrison, Anurag Kumar, John Hildebrand, Lynne Hodge, Russell Charif, Kathleen Dudzinski, and Ann Warde for help with project planning, field work support, and data management. For all the support and advice, thanks to the NEFSC Protected Species Branch, especially the passive acoustics group, Josh Hatch, and Leah Crowe. We thank the field and crew teams on all the ships that helped in the numerous deployments and recoveries. This research was funded and supported by many organizations, specified by projects as follows: data recordings from region 1 were provided by K. Stafford (funding: National Science Foundation #NSF‐ARC 0532611). Region 2 data: D. K. Mellinger and S. Nieukirk, National Oceanic and Atmospheric Administration (NOAA) PMEL contribution #5055 (funding: NOAA and the Office of Naval Research #N00014–03–1–0099, NOAA #NA06OAR4600100, US Navy #N00244‐08‐1‐0029, N00244‐09‐1‐0079, and N00244‐10‐1‐0047). Region 3A data: D. Risch (funding: NOAA and Navy N45 programs). Region 3 data: H. Moors‐Murphy and Fisheries and Oceans Canada (2005–2014 data), and the Whitehead Lab of Dalhousie University (eastern Scotian Shelf data; logistical support by A. Cogswell, J. Bartholette, A. Hartling, and vessel CCGS Hudson crew). Emerald Basin and Roseway Basin Guardbuoy data, deployment, and funding: Akoostix Inc. Region 3 Emerald Bank and Roseway Basin 2004 data: D. K. Mellinger and S. Nieukirk, NOAA PMEL contribution #5055 (funding: NOAA). Region 4 data: S. Parks (funding: NOAA and Cornell University) and E. Summers, S. Todd, J. Bort Thornton, A. N. Rice, and C. W. Clark (funding: Maine Department of Marine Resources, NOAA #NA09NMF4520418, and #NA10NMF4520291). Region 5 data: S. M. Van Parijs, D. Cholewiak, L. Hatch, C. W. Clark, D. Risch, and D. Wiley (funding: National Oceanic Partnership Program (NOPP), NOAA, and Navy N45). Region 6 data: S. M. Van Parijs and D. Cholewiak (funding: Navy N45 and Bureau of Ocean and Energy Management (BOEM) Atlantic Marine Assessment Program for Protected Species [AMAPPS] program). Region 7 data: A. N. Rice, H. Klinck, A. Warde, B. Martin, J. Delarue, and S. Kraus (funding: New York State Department of Environmental Conservation, Massachusetts Clean Energy Center, and BOEM). Region 8 data: G. Buchanan, and K. Dudzinski (funding: New Jersey Department of Environmental Protection and the New Jersey Clean Energy Fund) and A. N. Rice, C. W. Clark, and H. Klinck (funding: Center for Conservation Bioacoustics at Cornell University and BOEM). Region 9 data: J. E. Stanistreet, J. Bell, D. P. Nowacek, A. J. Read, and S. M. Van Parijs (funding: NOAA and US Fleet Forces Command). Region 10 data: L. Garrison, M. Soldevilla, C. W. Clark, R. A. Chariff, A. N. Rice, H. Klinck, J. Bell, D. P. Nowacek, A. J. Read, J. Hildebrand, A. Kumar, L. Hodge, and J. E. Stanistreet (funding: US Fleet Forces Command, BOEM, NOAA, and NOPP). Region 11 data: C. Berchok as part of a collaborative project led by the Fundacion Dominicana de Estudios Marinos, Inc. (Dr. Idelisa Bonnelly de Calventi; funding: The Nature Conservancy [Elianny Dominguez]) and D. Risch (funding: World Wildlife Fund, NOAA, and Dutch Ministry of Economic Affairs)

Amplification and demultiplexing in insulin-regulated Akt protein kinase pathway in adipocytes.

Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver. Here, we show that in 3T3-L1 adipocytes, Akt operates optimally over a limited dynamic range. This indicates that Akt is a highly sensitive amplification step in the pathway. With robust insulin stimulation, substantial changes in Akt phosphorylation using either pharmacologic or genetic manipulations had relatively little effect on Akt activity. By integrating these data we observed that half-maximal Akt activity was achieved at a threshold level of Akt phosphorylation corresponding to 5-22% of its full dynamic range. This behavior was also associated with lack of concordance or demultiplexing in the behavior of downstream components. Most notably, FoxO1 phosphorylation was more sensitive to insulin and did not exhibit a change in its rate of phosphorylation between 1 and 100 nm insulin compared with other substrates (AS160, TSC2, GSK3). Similar differences were observed between various insulin-regulated pathways such as GLUT4 translocation and protein synthesis. These data indicate that Akt itself is a major amplification switch in the insulin signaling pathway and that features of the pathway enable the insulin signal to be split or demultiplexed into discrete outputs. This has important implications for the role of this pathway in disease