The edge of the M87 halo and the kinematics of the diffuse light in the Virgo cluster core

We present high resolution FLAMES/VLT spectroscopy of intracluster planetary nebula (ICPN) candidates, targeting three new fields in the Virgo cluster core with surface brightness down to mu_B = 28.5. Based on the projected phase space information we separate the old and 12 newly-confirmed PNs into galaxy and intracluster components. The M87 PNs are confined to the extended stellar envelope of M87, within a projected radius of ~ 160 kpc, while the ICPNs are scattered across the whole surveyed region between M87 and M86. The velocity dispersions determined from the M87 PNs at projected radii of 60 kpc and 144 kpc show that the galaxy's velocity dispersion profile decreases in the outer halo, down to 78 +/- 25 km/s. A Jeans model for the M87 halo stars in the gravitational potential traced by the X-ray emission fits the observed velocity dispersion profile only if the stellar orbits are strongly radially anisotropic (beta ~= 0.4 at r ~= 10 kpc increasing to 0.8 at the outer edge), and if additionally the stellar halo is truncated at ~= 150 kpc average elliptical radius. From the spatial and velocity distribution of the ICPNs we infer that M87 and M86 are falling towards each other and that we may be observing them just before the first close pass. The inferred luminosity-specific PN numbers for the M87 halo and the ICL are in the range of values observed for old (> 10 Gyr) stellar populations (abridged).Comment: Accepted for publication in Astronomy and Astrophysics. 16 pages, 14 figures and 4 table

Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

<p>Abstract</p> <p>Background</p> <p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences.</p> <p>Methods</p> <p>In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses.</p> <p>Results</p> <p>Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (<it>P </it>> 0.05). The expected sex difference in favor of heavier males was not seen (<it>P </it>> 0.05). Of the 105 subjects, 44 (27%; 34 females, 10 males) had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (<it>P </it>= 0.0082). The expected sex difference in favor of longer males was also not seen (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants.</p

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index : a mendelian randomisation study

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10−7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA

Predictors of microvascular reperfusion after myocardial infarction

Purpose of Review: In acute ST-segment elevation myocardial infarction (STEMI), successful restoration of blood flow in the infarct-related coronary artery may not secure effective myocardial reperfusion. The mortality and morbidity associated with acute MI remain significant. Microvascular obstruction (MVO) represents failed microvascular reperfusion. MVO is under-recognized, independently associated with adverse cardiac prognosis and represents an unmet therapeutic need. Recent Findings: Multiple factors including clinical presentation, patient characteristics, biochemical markers, and imaging parameters are associated with MVO after MI. Summary: Impaired microvascular reperfusion is common following percutaneous coronary intervention (PCI). New knowledge about disease mechanisms underpins precision medicine with individualized risk assessment, investigation, and stratified therapy. To date, there are no evidence-based therapies to prevent or treat MVO post-MI. Identifying novel therapy for MVO is the next frontier

Expansion velocities and core masses of bright planetary nebulae in the Virgo cluster

The line-of-sight velocities and [OIII] 5007 AA expansion velocities are measured for 11 planetary nebulae (PNs) in the Virgo cluster core, at 15 Mpc distance, with the FLAMES spectrograph on the ESO VLT. These PNs are located about halfway between the two giant ellipticals M87 and M86. From the [OIII] 5007 AA line profile widths, the average half-width at half maximum expansion velocity for this sample of 11 PNs is v_HWHM = 16.5 km/s (RMS=2.6 km/s). We use the PN subsample bound to M87 to remove the distance uncertainties, and the resulting [OIII] 5007 AA luminosities to derive the central star masses. We find these masses to be at least 0.6 M_sun and obtain PN observable life times t_PN < 2000 yrs, which imply that the bright PNs detected in the Virgo cluster core are compact, high density nebulae. We finally discuss several scenarios for explaining the high central star masses in these bright M87 halo PNs.Comment: In press on Astrophysical Journal Letters, 12 pages, 3 figure

Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies

Autonomous Microbial Sampler (AMS), a device for the uncontaminated collection of multiple microbial samples from submarine hydrothermal vents and other aquatic environments

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 53 (2006): 894-916, doi:10.1016/j.dsr.2006.01.009.An Autonomous Microbial Sampler (AMS) is described that will obtain uncontaminated and exogenous DNA-free microbial samples from most marine, fresh water and hydrothermal ecosystems. Sampling with the AMS may be conducted using manned submersibles, Remotely Operated Vehicles (ROVs), Autonomous Underwater Vehicles (AUVs), or when tethered to a hydrowire during hydrocast operations on research vessels. The modular device consists of a titanium nozzle for sampling in potentially hot environments (>350°C) and fluid-handling components for the collection of six independent filtered or unfiltered samples. An onboard microcomputer permits sampling to be controlled by the investigator, by external devices (e.g., AUV computer), or by internal programming. Temperature, volume pumped and other parameters are recorded during sampling. Complete protection of samples from microbial contamination was observed in tests simulating deployment of the AMS in coastal seawater, where the sampling nozzle was exposed to seawater containing 1x106 cells ml-1 of a red pigmented tracer organism, Serratia marinorubra. Field testing of the AMS at a hydrothermal vent field was successfully undertaken in 2000. Results of DNA destruction studies have revealed that exposure of samples of the Eukaryote Euglena and the bacterium S. marinorubra to 0.5 N sulfuric acid at 23°C for 1 hour was sufficient to remove Polymerase Chain Reaction (PCR) amplifiable DNA. Studies assessing the suitability of hydrogen peroxide as a sterilizing and DNA-destroying agent showed that 20 or 30% hydrogen peroxide sterilized samples of Serratia in 1 hr and destroyed the DNA of Serratia, in 3 hrs, but not 1 or 2 hrs. DNA AWAY™ killed Serratia and destroyed the DNA of both Serratia and the vent microbe (GB-D) of the genus Pyrococcus in 1 hour.This work was supported by a DOC/NOAA Small Business Innovative Research Award, Contract No. 50-DKNA-9-90116 awarded to McLane Research Laboratories, Inc. and (via subcontract) to the Woods Hole Oceanographic Institution. Some of the microbial testing work was also supported by the National Science Foundation, Grant No. IBN-0131557 and the Woods Hole Oceanographic Inst. Deep Ocean Exploration Institute Grant No. 25051131

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies