Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk:A Mendelian randomization analysis

BACKGROUND The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. METHODS We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). RESULTS In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. CONCLUSIONS We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies

Is a minor-merger driving the nuclear activity in the Seyfert 2 galaxy NGC 2110?

We report on a detailed morphological and kinematic study of the isolated non-barred nearby Seyfert 2 galaxy NGC 2110. We combine Integral Field optical spectroscopy, with long-slit and WFPC2 imaging available in the HST archive to investigate the fueling mechanism in this galaxy. Previous work (Wilson & Baldwin 1985) concluded that the kinematic center of the galaxy is displaced \~220 pc from the apparent mass center of the galaxy, and the ionized gas follows a remarkably normal rotation curve. Our analysis based on the stellar kinematics, 2D ionized gas velocity field and dispersion velocity, and high spatial resolution morphology at V, I and Halpha reveals that: 1) The kinematic center of NGC 2110 is at the nucleus of the galaxy. 2) The ionized gas is not in pure rotational motion. 3) The morphology of the 2D distribution of the emission line widths suggests the presence of a minor axis galactic outflow. 4) The nucleus is blue-shifted with respect to the stellar systemic velocity, suggesting the NLR gas is out-flowing due to the interaction with the radio jet. 5) The ionized gas is red-shifted ~100 km/s over the corresponding rotational motion south of the nucleus, and 240 km/s with respect to the nuclear stellar systemic velocity. This velocity is coincident with the HI red-shifted absorption velocity detected by Gallimore et al (1999). We discuss the possibility that the kinematics of the south ionized gas could be perturbed by the collision with a small satellite that impacted on NGC 2110 close to the center with a highly inclined orbit. Additional support for this interpretation are the radial dust lanes and tidal debris detected in the V un-sharp masked image. We suggest that a minor-merger may have driven the nuclear activity in NGC 2110.Comment: Full resolution images at http://www.iaa.csic.es/~rosa/preprints/preprints.html or at http://www.journals.uchicago.edu/ApJ/future.htm

Stellar Population in LLAGN.I: Ground-based observations

(Abridge): We present a spectroscopic study of the stellar populations of Low Luminosity AGN (LLAGN). Our main goal is to determine whether the stars who live in the innermost (100 pc-scale) regions of these galaxies are in some way related to the emission line properties, which would imply a link between the stellar population and the ionization mechanism. High signal to noise, ground based long-slit spectra in the 3500--5500 A interval were collected for 60 galaxies.Our main findings are: (1) Few LLAGN have a detectable young (< 10 Myr) starburst component, indicating that very massive stars do not contribute significantly to the optical continuum. In particular, no features due to Wolf-Rayet stars were convincingly detected. (2) High Order Balmer absorption lines of HI (HOBLs), on the other hand, are detected in 40% of LLAGN. These features, which are strongest in 100 Myr--1 Gyr intermediate age stellar populations, are accompanied by diluted metal absorption lines and bluer colors than other objects in the sample. (3) These intermediate age populations are very common (50 %) in LLAGN with relatively weak [OI] emission, but rare (10 %) in LLAGN with stronger [OI]. This is intriguing since LLAGN with weak [OI] have been previously hypothesized to be ``transition objects'' in which both an AGN and young stars contribute to the emission-line excitation. Massive stars, if present, are completely outshone by intermediate age and old stars in the optical. This happens in at least a couple of objects where independent UV spectroscopy detects young starbursts not seen in the optical. (4) Objects with predominantly old stars span the whole range of [OI]/Halpha values, but (5) sources with significant young and/or intermediate age populations are nearly all (90%) weak [OI] emitters.Comment: To be published in ApJ (April issue). Paper with full resolution images is at: http://www.iaa.csic.es/~rosa/preprints/preprints.html http://www.journals.uchicago.edu/ApJ/journa

Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants.

Auriculocondylar syndrome 2 (ARCND2) is a rare autosomal dominant craniofacial malformation syndrome linked to multiple genetic variants in the coding sequence of phospholipase C β4 (PLCB4). PLCB4 is a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway, which establishes the identity of neural crest cells (NCCs) that form lower jaw and middle ear structures. However, the functional consequences of PLCB4 variants on EDNRA signaling is not known. Here, we show, using multiple signaling reporter assays, that known PLCB4 variants resulting from missense mutations exert a dominant-negative interference over EDNRA signaling. In addition, using CRISPR/Cas9, we find that F0 mouse embryos modeling one PLCB4 variant have facial defects recapitulating those observed in hypomorphic Ednra mouse models, including a bone that we identify as an atavistic change in the posterior palate/oral cavity. Remarkably, we have identified a similar osseous phenotype in a child with ARCND2. Our results identify the disease mechanism of ARCND2, demonstrate that the PLCB4 variants cause craniofacial differences and illustrate how minor changes in signaling within NCCs may have driven evolutionary changes in jaw structure and function. This article has an associated First Person interview with the first author of the paper

Impacts of Invasive, Exotic Grasses on Quail of Southwestern Rangelands: A Decade of Progress?

Exotic grass invasions are a serious concern for State and Federal agencies, non-government organizations, and private landowners engaged in quail conservation and management. Quail biologists recognized the potential negative impacts of exotic grass invasion on North American quail populations 2 decades ago. This issue was addressed in a review paper published in the Proceedings of the 5th National Quail Symposium in 2002. That paper reported the state of our knowledge on impacts of exotic grass invasions on 5 quail species inhabiting southwestern rangelands. Our objective is to update the progress of exotic grass-quail research on southwestern rangelands during the past decade by reviewing studies that provide specific results about the impacts of exotic grass invasions on southwestern quail populations. Results of studies that have quantified the impacts of exotic grass on quail habitat use are summarized and discussed along with studies that describe how exotic grasses impact important components of quail habitat such as diversity and abundance native herbaceous plants and arthropods. Management of exotic grasses is also discussed

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. Methods: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. Results: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. Conclusion: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.</p

Ultraviolet-Optical observations of the Seyfert 2 Galaxies NGC 7130, NGC 5135 and IC 3639: Implications for the Starburst-AGN Connection

We present and discuss HST (WFPC2 and FOC) images and UV GHRS spectra plus ground-based near UV through to near IR spectra of three Seyfert 2 nuclei (NGC 7130, NGC 5135 and IC 3639). These galaxies, together to Mrk 477, were selected from a bigger sample that comprises the 20 brightest Seyfert 2 nuclei, with the goal to study the origin of the UV-optical-near IR featureless continuum in Seyfert 2 nuclei. These four galaxies have bolometric luminosities, as computed with the four IRAS bands, of 10^11 Lsol. They are close enough to be resolved with HST the nuclear zone. This makes these Seyfert 2 galaxies benchmarks to study the Starburst-AGN connection in more distant galaxies. The data provide direct evidence of the existence of a central nuclear starburst that dominates the UV light, and that seem to be responsible for the origin of the so called featureless continuum. These starbursts are dusty and compact. They have sizes (from less than 100 pc to a few hundred pc) much smaller and closer to the nucleus than that seen in the prototype Seyfert 2 galaxy NGC 1068. The bolometric luminosity of these starbursts is similar to the estimated bolometric luminosities of their obscured Seyfert 1 nuclei, and thus they contribute in the same amount to the overall energetics of these galaxies.Comment: to be published in ApJ 505, September issue. The figures are in a tar files at: http://www.iaa.es/~rosa/Seyfert

Benchmark Evaluation of True Single Molecular Sequencing to Determine Cystic Fibrosis Airway Microbiome Diversity

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic fibrosis lungs. Paired sputa were also obtained from three study participants with CF before and \u3e6 days after initiation of antibiotics. Antibiotic resistant B. cepacia and P. aeruginosa were identified in concurrently obtained respiratory cultures. Direct sequencing was performed using tSMS, and filtered reads were aligned to reference genomes from NCBI using PathoScope and Kraken and unique clade-specific marker genes using MetaPhlAn. A total of 180-518K of 6-12 million filtered reads were aligned for each sample. Detection of known pathogens in control samples was most successful using PathoScope. In the CF sputa, alpha diversity measures varied based on the alignment method used, but similar trends were found between pre- and post-antibiotic samples. PathoScope outperformed Kraken and MetaPhlAn in our validation study of artificial bacterial community controls and also has advantages over Kraken and MetaPhlAn of being able to determine bacterial strains and the presence of fungal organisms. PathoScope can be confidently used when evaluating metagenomic data to determine CF airway microbiome diversity

Exploring the origin of lithium, carbon, strontium, and barium with four new ultra metal-poor stars

We present an elemental abundance analysis for four newly discovered ultra metal-poor stars from the Hamburg/ESO survey, with [Fe/H] ≤ -4. Based on high-resolution, high signal-to-noise spectra, we derive abundances for 17 elements in the range from L