New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

First simultaneous global measurements of nighttime stratospheric NO₂ and NO₃ observed by Global Ozone Monitoring by Occultation of Stars (GOMOS)/Envisat in 2003

International audienceThe Global Ozone Monitoring by Occultation of Stars (GOMOS) stellar occultation instrument on board the Envisat European satellite provides global coverage of ozone and other stratospheric species with good vertical resolution and a self-calibrating method. In this paper we present the first simultaneous global distribution of stratospheric NO2 and NO3 from 1 year of nighttime GOMOS data in 2003. Most previous NO2 satellite observations have been made using the solar occultation technique. They are difficult to interpret due to the fast photochemical evolution of NO2 at sunrise and sunset. There are no published observations of NO3 from space because this constituent is rapidly photodissociated during daytime and is not observable by solar occultation. It is shown that the NO2 mixing ratio reaches a maximum around 40 km with values between 14 and 16 ppbv at low and middle latitudes. The global distribution of NO2 observed by GOMOS is very similar to the NO + NO2 Halogen Occultation Experiment climatology deduced from sunset measurements from 1999 to 2004. At high latitude a high mixing ratio is observed in the north vortex in November 2003 after a strong solar proton event and in the south vortex in July 2003. The NO3 mixing ratio peaks at 40–45 km. NO3 follows a semiannual variation at low latitudes with maxima at equinoxes and an annual variation at middle and high latitudes with a maximum in summer. In the upper stratosphere the mixing ratio of NO3 is strongly correlated with temperature due to the thermal dependence of its formation rate. Citation: Hauchecorne, A., et al. (2005), First simultaneous global measurements of nighttime stratospheric NO2 and NO3 observed by Global Ozone Monitoring by Occultation of Stars (GOMOS)/Envisat in 200

NO3 vertical profile measurements from remote sensing balloon-borne spectrometers and comparison with model calculations

Eleven vertical profiles of stratospheric NO3 have been obtained since 1992 using the AMON and SALOMON balloon-borne UV-visible spectrometers. The measurements are compared to the SLIMCAT 3D model and calculations based on the steady-state hypothesis for NO3. The calculations cannot reproduce some parts of the profiles which exhibit strong concentration fluctuations over few kilometres, as a consequence of the dependence of NO3 on local temperature variations. A statistical use of the data allows us to estimate the influence of the temperature dependence of the absorption cross-section on the data analysis, and the validity of the recommended reaction rates available in the literature. Discrepancies exist between the model based on recommended kinetics and observations at warmer temperatures. Nevertheless, the analysis is biased by local temperature inhomogeneities, and only a low-resolution vertical shape of the NO3 profiles can be retrieved

A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against <i>Mycobacterium tuberculosis</i>

<div><p>Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG) vaccine, infection by <i>Mycobacterium tuberculosis</i> (Mtb) remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance. Immunotherapy constitutes a promising approach to improving current antibiotic treatments through engagement of the host’s immune system. We designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara (MVA) virus, denoted MVATG18598, which expresses ten antigens classically described as representative of each of different phases of Mtb infection. <i>In vitro</i> analysis coupled with multiple-passage evaluation demonstrated that this vaccine is genetically stable, <i>i</i>.<i>e</i>. fit for manufacturing. Using different mouse strains, we show that MVATG18598 vaccination results in both Th1-associated T-cell responses and cytolytic activity, targeting all 10 vaccine-expressed Mtb antigens. In chronic post-exposure mouse models, MVATG18598 vaccination in combination with an antibiotic regimen decreases the bacterial burden in the lungs of infected mice, compared with chemotherapy alone, and is associated with long-lasting antigen-specific Th1-type T cell and antibody responses. In one model, co-treatment with MVATG18598 prevented relapse of the disease after treatment completion, an important clinical goal. Overall, results demonstrate the capacity of the therapeutic MVATG18598 vaccine to improve efficacy of chemotherapy against TB. These data support further development of this novel immunotherapeutic in the treatment of Mtb infections.</p></div

Statistical analyses of bacterial load of pooled post-exposure experiments performed in both BALB/c and C57BL/6 mouse models.

<p>Groups of mice co-treated with antibiotics (ATB) and MVATG18598 or MVATGN33.1 given thrice subcutaneously during antibiotic therapy were analyzed.</p

Statistical analyses of reactivation of pooled post-exposure experiments performed in both BALB/c and C57BL/6 mouse models.

<p>Groups of mice co-treated with antibiotics (ATB) and MVATG18598 or MVATGN33.1 given thrice subcutaneously during antibiotic therapy were analyzed.</p