Phenotypic analysis of peripheral B cell populations during Mycobacterium tuberculosis infection and disease

Abstract Background Mycobacterium tuberculosis (Mtb) remains an unresolved threat resulting in great annual loss of life. The role of B cells during the protective immunity to Mtb is still unclear. B cells have been described as effector cells in addition to their role as antibody producing cells during disease. Here we aim to identify and characterize the frequency of peripheral B-cell subpopulations during active Tuberculosis and over treatment response. Analysis were done for both class switched (CS) and non-class switched (NCS) phenotypes. Methods We recruited participants with active untreated pulmonary Tuberculosis, other lung diseases and healthy community controls. All groups were followed up for one week from recruitment and the TB cases till the end of treatment (month 6). Results Peripheral blood samples were collected, stained with monoclonal antibodies to CD19 + cells, Immunoglobulin (Ig) M, plasma cells (CD 138 + ), marker of memory (CD27 + ), immune activation (CD23 + ) and acquired on a flow cytometer. Circulating Marginal zone B cells (CD19 + IgM + CD23 − CD27 + ) and memory phenotypes are able to distinguish between TB diagnosis and end of treatment. The frequency of mature B cells from TB cases are lower than that of other-lung diseases at diagnosis. A subpopulation of activated memory B cells (CD19 + IgM + CD23 + CD27 + ) cells are present at the end of TB treatment. Conclusions This study identified distinctive B cell subpopulations present during active TB disease and other lung disease conditions. These cell populations warrants further examination in larger studies as it may be informative as cell markers or as effectors/regulators in TB disease or TB treatment response

Faire l’Union. La refondation des parties de droite après les élections de 2002

Un nouveau parti de droite, pour le moment dénommé UMP, a été mis en place entre des deux tours de l'élection présidentielle. Cet article se donne pour objectif d'analyser les enjeux de cette transformation. La genèse de l'UMP permet de saisir dans quelle mesure un parti poli-tique peut être conçu comme la connexion d'un ensemble de systèmes de coopération organisés autour de postes à conquérir. En effet, l'impératif d'unification de la droite française est lié au décalage persistant existant entre les systèmes de coopération législatif et présidentiel. Mais les questions soulevées par cette fusion partisane (l'UMP inclut le RPR, DL et une majeure partie de l'UDF) montrent que cette vision ne peut suffire et que les partis ne sont pas seulement des systèmes de coopération mais aussi des systèmes de production. Dès lors, leurs logiques d'organisation internes pèsent sur ce travail de transformation du social en politique, de la plu-ralité en homogénéité. Dans le cas de l'UMP, il s'agit d'abord de mettre en commun des modes de fonctionnement, en particulier de définir la place et la légitimité accordées respectivement aux adhérents et aux élus, mais aussi d'organiser l'expression de la pluralité idéologique par la mise en place de courants

Solar wind sputtering of dust on the surface of 67P/Churyumov-Gerasimenko

International audienceFar away from the Sun, at around 3 AU, the activity of comet 67P/Churyumov-Gerasimenko is low and changes with local time (solar insolation), with location (chemical heterogeneity of the surface), and with season. When the activity is very low because the total cross section of the comet against the Sun is small, the solar wind has access to the surface of the comet and causes ion-induced sputtering of surface material, which we wish to observe.Methods. We used the Double Focussing Mass Spectrometer (DFMS) of the ROSINA experiment on ESA’s Rosetta mission to search for mass spectrometric evidence of sputtered refractory species. In high-resolution mode, DFMS can separate some of the mass peaks of refractory elements from the many volatile species present in the coma.Results. At present, the locations of solar wind surface access are in the southern hemisphere of the comet (the local winter). Of particular interest is sputtering of dust grains on the surface. We observe global averages over the winter hemisphere of the refractory elements Na, K, Si, and Ca, presumably sputtered from grains residing on the surface. Compared to carbonaceous chondrites, the comet has the same Na abundance, is depleted in Ca, and has an excess of K. In addition, for Si the signal strength is strong enough to compile a coarse compositional map of the southern hemisphere. Most, perhaps all, of the observed variation can be explained by the solar wind being affected by the atmosphere of the comet

Turbulence Heating ObserveR – satellite mission proposal

The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p&lt;1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p&lt;5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.</p

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response

Space plasma physics science opportunities for the lunar orbital platform - Gateway

The Lunar Orbital Platform - Gateway (LOP - Gateway, or simply Gateway) is a crewed platform that will be assembled and operated in the vicinity of the Moon by NASA and international partner organizations, including ESA, starting from the mid-2020s. It will offer new opportunities for fundamental and applied scientific research. The Moon is a unique location to study the deep space plasma environment. Moreover, the lunar surface and the surface-bounded exosphere are interacting with this environment, constituting a complex multi-scale interacting system. This paper examines the opportunities provided by externally mounted payloads on the Gateway in the field of space plasma physics, heliophysics and space weather, and also examines the impact of the space environment on an inhabited platform in the vicinity of the Moon. It then presents the conceptual design of a model payload, required to perform these space plasma measurements and observations. It results that the Gateway is very well-suited for space plasma physics research. It allows a series of scientific objectives with a multi-disciplinary dimension to be addressed

How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

Background The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.Peer reviewe