Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

High Spectral Resolution Measurement of the Sunyaev–Zel'dovich Effect Null with Z-Spec

The Sunyaev-Zel'dovich (SZ) effect spectrum crosses through a null where ΔT_CMB = 0 near ν_0 = 217 GHz. In a cluster of galaxies, ν0 can be shifted from the canonical thermal SZ effect value by corrections to the SZ effect scattering due to the properties of the inter-cluster medium. We have measured the SZ effect in the hot galaxy cluster RX J 1347.5 – 1145 with Z-Spec, an R ~ 300 grating spectrometer sensitive between 185 and 305 GHz. These data comprise a high spectral resolution measurement around the null of the SZ effect and clearly exhibit the transition from negative to positive ΔT_CMB over the Z-Spec band. The SZ null position is measured to be ν_0 = 225.8 ± 2.5(stat.) ± 1.2(sys.) GHz, which differs from the canonical null frequency by 3.0σ and is evidence for modifications to the canonical thermal SZ effect shape. Assuming the measured shift in ν0 is due only to relativistic corrections to the SZ spectrum, we place the limit kT_e = 17.1 ± 5.3 keV from the zero-point measurement alone. By simulating the response of the instrument to the sky, we are able to generate likelihood functions in {y_0, T_e, v_pec} space. For v_pec = 0 km s^(–1), we measure the best-fitting SZ model to be y_0 = 4.6^(+0.6)_(–0.9) × 10^(–4), T_e, 0 = 15.2^(+12)_(–7.4) keV. When v pec is allowed to vary, a most probable value of v_pec = + 450 ± 810 km s^(–1) is found

Ground vehicle control at NIST: From teleoperation to autonomy

NIST is applying their Real-time Control System (RCS) methodology for control of ground vehicles for both the U.S. Army Researh Lab, as part of the DOD's Unmanned Ground Vehicles program, and for the Department of Transportation's Intelligent Vehicle/Highway Systems (IVHS) program. The actuated vehicle, a military HMMWV, has motors for steering, brake, throttle, etc. and sensors for the dashboard gauges. For military operations, the vehicle has two modes of operation: a teleoperation mode--where an operator remotely controls the vehicle over an RF communications network; and a semi-autonomous mode called retro-traverse--where the control system uses an inertial navigation system to steer the vehicle along a prerecorded path. For the IVHS work, intelligent vision processing elements replace the human teleoperator to achieve autonomous, visually guided road following

Doing Biopolitics Differently? Radical Potential in the Post-2015 MDG and SDG Debates

Post print On institutional repository or subject-based repository after a 18 months embargo, withdraw

The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). © 2006 Nature Publishing Group

Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression

Background: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Methods: Pregnant women with mild asthma (n¼52), moderate-severe asthma (n¼71) and without asthma (n¼51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Results Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p¼0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r¼_0.286, p¼0.017) and, despite a decrease in placental GR mRNA (p¼0.003), placental GRa protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. Conclusions The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or posttranslational modifications.Nicolette A Hodyl, Hayley Wyper, Annette Osei-Kumah, Naomi Scott, Vanessa E Murphy, Peter Gibson, Roger Smith and Vicki L Clifto

The physical scale of the far-infrared emission in the most luminous submillimetre galaxies II: evidence for merger-driven star formation

We present high-resolution 345 GHz interferometric observations of two extreme luminous (L_{IR}>10^{13} L_sun), submillimetre-selected galaxies (SMGs) in the COSMOS field with the Submillimeter Array (SMA). Both targets were previously detected as unresolved point-sources by the SMA in its compact configuration, also at 345 GHz. These new data, which provide a factor of ~3 improvement in resolution, allow us to measure the physical scale of the far-infrared in the submillimetre directly. The visibility functions of both targets show significant evidence for structure on 0.5-1 arcsec scales, which at z=1.5 translates into a physical scale of 5-8 kpc. Our results are consistent with the angular and physical scales of two comparably luminous objects with high-resolution SMA followup, as well as radio continuum and CO sizes. These relatively compact sizes (<5-10 kpc) argue strongly for merger-driven starbursts, rather than extended gas-rich disks, as the preferred channel for forming SMGs. For the most luminous objects, the derived sizes may also have important physical consequences; under a series of simplifying assumptions, we find that these two objects in particular are forming stars close to or at the Eddington limit for a starburst.Comment: 9 pages, 3 Figures, submitted to MNRA

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population