Pre-pregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: a prospective cohort study

Background Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the impact of vitamin D intake either from diet or from supplements on the development of gestational diabetes mellitus (GDM) remains unknown. We prospectively examined the association of pre-pregnancy habitual intake of vitamin D from diet and supplements with risk of incident GDM in a well-established cohort. Methods We included 21,356 singleton pregnancies from 15,225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intakes from food sources and supplements, was assessed in 1991 and every four years thereafter by validated food frequency questionnaires. We used log-binomial models with generalized estimating equations to estimate the relative risks (RRs) and 95% confidence intervals (CIs). Results We documented 865 incident GDM cases during 10 years of follow-up. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1–399, ≥ 400 IU/d were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (P for trend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Conclusions Pre-pregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. Our study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda

Objective To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda

The Morpho-kinematic Architecture of Super Star Clusters in the Center of NGC 253

The center of the nearby galaxy NGC 253 hosts a population of more than a dozen super star clusters (SSCs) that are still in the process of forming. The majority of the star formation of the burst is concentrated in these SSCs, and the starburst is powering a multiphase outflow from the galaxy. In this work, we measure the 350 GHz dust continuum emission toward the center of NGC 253 at 47 mas (0.8 pc) resolution using data from the Atacama Large Millimeter/submillimeter Array. We report the detection of 350 GHz (dust) continuum emission in the outflow for the first time, associated with the prominent South-West streamer. In this feature, the dust emission has a width of approximate to 8 pc, is located at the outer edge of the CO emission, and corresponds to a molecular gas mass of similar to(8-17)x10(6) M (circle dot). In the starburst nucleus, we measure the resolved radial profiles, sizes, and molecular gas masses of the SSCs. Compared to previous work at the somewhat lower spatial resolution, the SSCs here break apart into smaller substructures with radii 0.4-0.7 pc. In projection, the SSCs, dust, and dense molecular gas appear to be arranged as a thin, almost linear, structure roughly 155 pc in length. The morphology and kinematics of this structure can be well explained as gas following x (2) orbits at the center of a barred potential. We constrain the morpho-kinematic arrangement of the SSCs themselves, finding that an elliptical, angular-momentum-conserving ring is a good description of both the morphology and kinematics of the SSCs

Outflows from Super Star Clusters in the Central Starburst of NGC253

Young massive clusters play an important role in the evolution of their host galaxies, and feedback from the high-mass stars in these clusters can have profound effects on the surrounding interstellar medium. The nuclear starburst in the nearby galaxy NGC253 at a distance of 3.5 Mpc is a key laboratory in which to study star formation in an extreme environment. Previous high resolution (1.9 pc) dust continuum observations from ALMA discovered 14 compact, massive super star clusters (SSCs) still in formation. We present here ALMA data at 350 GHz with 28 milliarcsecond (0.5 pc) resolution. We detect blueshifted absorption and redshifted emission (P-Cygni profiles) towards three of these SSCs in multiple lines, including CS 7$-$6 and H$^{13}$CN 4$-$3, which represents direct evidence for previously unobserved outflows. The mass contained in these outflows is a significant fraction of the cluster gas masses, which suggests we are witnessing a short but important phase. Further evidence of this is the finding of a molecular shell around the only SSC visible at near-IR wavelengths. We model the P-Cygni line profiles to constrain the outflow geometry, finding that the outflows must be nearly spherical. Through a comparison of the outflow properties with predictions from simulations, we find that none of the available mechanisms completely explains the observations, although dust-reprocessed radiation pressure and O star stellar winds are the most likely candidates. The observed outflows will have a very substantial effect on the clusters' evolution and star formation efficiency.Comment: Accepted to Ap

Super Star Clusters in the Central Starburst of NGC 4945

The nearby (3.8Mpc) galaxy NGC 4945 hosts a nuclear starburst and Seyfert type 2 active galactic nucleus (AGN). We use the Atacama Large Millimeter/submillimeter Array (ALMA) to image the 93 GHz (3.2 mm) free-free continuum and hydrogen recombination line emission (H40 alpha and H42 alpha) at 2.2 pc (0 12) resolution. Our observations reveal 27 bright, compact sources with FWHM sizes of 1.4-4.0 pc, which we identify as candidate super star clusters. Recombination line emission, tracing the ionizing photon rate of the candidate clusters, is detected in 15 sources, six of which have a significant synchrotron component to the 93 GHz continuum. Adopting an age of similar to 5Myr, the stellar masses implied by the ionizing photon luminosities are log(10) (M*/M-circle dot) approximate to 4.7-6.1. We fit a slope to the cluster mass distribution and find beta = -1.8 +/-.0.4. The gas masses associated with these clusters, derived from the dust continuum at 350 GHz, are typically an order of magnitude lower than the stellar mass. These candidate clusters appear to have already converted a large fraction of their dense natal material into stars and, given their small freefall times of similar to 0.05 Myr, are surviving an early volatile phase. We identify a pointlike source in 93 GHz continuum emission that is presumed to be the AGN. We do not detect recombination line emission from the AGN and place an upper limit on the ionizing photons that leak into the starburst region of Q(0).<.10(52) s(-1)

Extensive Genetic Diversity and Substructuring Among Zebrafish Strains Revealed through Copy Number Variant Analysis

Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNV elements exhibited strain specificity, with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen's large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and substructure of these commonly used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype and, if not properly addressed, such extensive levels of germ-line variation and population substructure in this commonly used model organism can potentially confound studies intended for translation to human diseases.Stem Cell and Regenerative Biolog

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

Hidden Gems on a Ring: Infant Massive Clusters and Their Formation Timeline Unveiled by ALMA, HST, and JWST in NGC 3351

We use 0.1″ observations from the Atacama Large Millimeter Array (ALMA), Hubble Space Telescope (HST), and JWST to study young massive clusters (YMCs) in their embedded “infant” phase across the central starburst ring in NGC 3351. Our new ALMA data reveal 18 bright and compact (sub-)millimeter continuum sources, of which 8 have counterparts in JWST images and only 6 have counterparts in HST images. Based on the ALMA continuum and molecular line data, as well as ancillary measurements for the HST and JWST counterparts, we identify 14 sources as infant star clusters with high stellar and/or gas masses (∼105 M ⊙), small radii (≲ 5 pc), large escape velocities (6–10 km s−1), and short freefall times (0.5–1 Myr). Their multiwavelength properties motivate us to divide them into four categories, likely corresponding to four evolutionary stages from starless clumps to exposed H ii region–cluster complexes. Leveraging age estimates for HST-identified clusters in the same region, we infer an evolutionary timeline, ranging from ∼1–2 Myr before cluster formation as starless clumps, to ∼4–6 Myr after as exposed H ii region–cluster complexes. Finally, we show that the YMCs make up a substantial fraction of recent star formation across the ring, exhibit a nonuniform azimuthal distribution without a very coherent evolutionary trend along the ring, and are capable of driving large-scale gas outflows

Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

Endometrial cancer is the most common gynecologic malignancy in developed countries and little is known about the underlying mechanism of stage and disease outcomes. The goal of this study was to identify differentially expressed genes (DEG) between late vs. early stage endometrioid adenocarcinoma (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in each of the two histological subtypes.Gene expression profiles of 20 cancer samples were analyzed (EAC = 10, USC = 10) using the human genome wide illumina bead microarrays. There was little overlap in the DEG sets between late vs. early stages in EAC and USC, and there was an insignificant overlap in DEG sets between good and poor prognosis in EAC and USC. Remarkably, there was no overlap between the stage-derived DEGs and the prognosis-derived DEGs for each of the two histological subtypes. Further functional annotation of differentially expressed genes showed that the composition of enriched function terms were different among different DEG sets. Gene expression differences for selected genes of various stages and outcomes were confirmed by qRT-PCR with a high validation rate.This data, although preliminary, suggests that there might be involvement of distinct groups of genes in tumor progression (late vs. early stage) in each of the EAC and USC. It also suggests that these genes are different from those involved in tumor outcome (good vs. poor prognosis). These involved genes, once clinically verified, may be important for predicting tumor progression and tumor outcome