Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes.

Understanding how phenotypic differences between males and females arise from the sex-biased expression of nearly identical genomes can reveal important insights into the biology and evolution of a species. Among Anopheles mosquito species, these phenotypic differences include vectorial capacity, as it is only females that blood feed and thus transmit human malaria. Here, we use RNA-seq data from multiple tissues of four vector species spanning the Anopheles phylogeny to explore the genomic and evolutionary properties of sex-biased genes. We find that, in these mosquitoes, in contrast to what has been found in many other organisms, female-biased genes are more rapidly evolving in sequence, expression, and genic turnover than male-biased genes. Our results suggest that this atypical pattern may be due to the combination of sex-specific life history challenges encountered by females, such as blood feeding. Furthermore, female propensity to mate only once in nature in male swarms likely diminishes sexual selection of post-reproductive traits related to sperm competition among males. We also develop a comparative framework to systematically explore tissue- and sex-specific splicing to document its conservation throughout the genus and identify a set of candidate genes for future functional analyses of sex-specific isoform usage. Finally, our data reveal that the deficit of male-biased genes on the X Chromosomes in Anopheles is a conserved feature in this genus and can be directly attributed to chromosome-wide transcriptional regulation that de-masculinizes the X in male reproductive tissues

Inhibition of T Cell and Promotion of Natural Killer Cell Development by the Dominant Negative Helix Loop Helix Factor Id3

Bipotential T/natural killer (NK) progenitor cells are present in the human thymus. Despite their bipotential capacity, these progenitors develop predominantly to T cells in the thymus. The mechanisms controlling this developmental choice are unknown. Here we present evidence that a member(s) of the family of basic helix loop helix (bHLH) transcription factors determines lineage specification of NK/T cell progenitors. The natural dominant negative HLH factor Id3, which blocks transcriptional activity of a number of known bHLH factors, was expressed in CD34+ progenitor cells by retrovirus-mediated gene transfer. Constitutive expression of Id3 completely blocks development of CD34+ cells into T cells in a fetal thymic organ culture (FTOC). In contrast, development into NK cells in an FTOC is enhanced. Thus, the activity of a bHLH transcription factor is necessary for T lineage differentiation of bipotential precursors, in the absence of which a default pathway leading to NK cell development is chosen. Our results identify a molecular switch for lineage specification in early lymphoid precursors of humans

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

The relationship between body mass index and sleep in women with risk factors for gestational diabetes mellitus

OnlinePublBackground: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective: To explore the relationships between self‐reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy.Methods: Cross‐sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks’ gestation to evaluate sleep. BMI 5 days/ month was higher in class II and class III obesity (1.38 (1.03–1.85) and 1.34 (1.01– 1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25– 2.02), 2.68 (2.07–3.48), 4.35 (3.21–5.88) to 4.96 (3.65–6.74), respectively)). Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI.Pamela Acosta Reyes, Jincy Immanuel, William M. Hague, Helena Teede, Emily Hibbert, Christopher J. Nolan, Michael J. Peek, Vincent Wong, Jeffrey R. Flack, Mark McLean, Raiyomand Dalal, Jürgen Harreiter, Alexandra Kautzky, Willer, Rohit Rajagopal, Arianne Sweeting, Glynis P. Ross, Ngai Wah Cheung, David Simmon

Meta-Analysis of the Immunogenicity and Tolerability of Pandemic Influenza A 2009 (H1N1) Vaccines

Background: Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation. Methods: We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis. Results: Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (> = 70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses < = 6 μg (even with as little as 1.875 μg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines. Conclusions: Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed

Surface currents and winds at the Delaware Bay mouth

Knowledge of the circulation of estuaries and adjacent shelf waters has relied on hydrographic measurements, moorings, and local wind observations usually removed from the region of interest. Although these observations are certainly sufficient to identify major characteristics, they lack both spatial resolution and temporal coverage. High resolution synoptic observations are required to identify important coastal processes at smaller scales. Long observation periods are needed to properly sample low-frequency processes that may also be important. The introduction of high-frequency (HF) radar measurements and regional wind models for coastal studies is changing this situation. Here we analyze synoptic, high-resolution surface winds and currents in the Delaware Bay mouth over an eight-month period (October 2007 through May 2008). The surface currents were measured by two high-frequency radars while the surface winds were extracted from a data-assimilating regional wind model. To illustrate the utility of these monitoring tools we focus on two 45-day periods which previously were shown to present contrasting pictures of the circulation. One, the low-outflow period is from 1 October through 14 November 2007; the other is the high-outflow period from 3 March through 16 April 2008. The large-scale characteristics noted by previous workers are clearly corroborated. Specifically the M2 tide dominates the surface currents, and the Delaware Bay outflow plume is clearly evident in the low frequency currents. Several new aspects of the surface circulation were also identified. These include a map of the spatial variability of the M2 tide (validating an earlier model study), persistent low-frequency cross-mouth flow, and a rapid response of the surface currents to a changing wind field. However, strong wind episodes did not persist long enough to set up a sustained Ekman response

The On-orbit Calibrations for the Fermi Large Area Telescope

The Large Area Telescope (LAT) on--board the Fermi Gamma ray Space Telescope began its on--orbit operations on June 23, 2008. Calibrations, defined in a generic sense, correspond to synchronization of trigger signals, optimization of delays for latching data, determination of detector thresholds, gains and responses, evaluation of the perimeter of the South Atlantic Anomaly (SAA), measurements of live time, of absolute time, and internal and spacecraft boresight alignments. Here we describe on orbit calibration results obtained using known astrophysical sources, galactic cosmic rays, and charge injection into the front-end electronics of each detector. Instrument response functions will be described in a separate publication. This paper demonstrates the stability of calibrations and describes minor changes observed since launch. These results have been used to calibrate the LAT datasets to be publicly released in August 2009.Comment: 60 pages, 34 figures, submitted to Astroparticle Physic