Formation of the black-hole binary M33 X-7 via mass-exchange in a tight massive system

M33 X-7 is among the most massive X-Ray binary stellar systems known, hosting a rapidly spinning 15.65 Msun black hole orbiting an underluminous 70 Msun Main Sequence companion in a slightly eccentric 3.45 day orbit. Although post-main-sequence mass transfer explains the masses and tight orbit, it leaves unexplained the observed X-Ray luminosity, star's underluminosity, black hole's spin, and eccentricity. A common envelope phase, or rotational mixing, could explain the orbit, but the former would lead to a merger and the latter to an overluminous companion. A merger would also ensue if mass transfer to the black hole were invoked for its spin-up. Here we report that, if M33 X-7 started as a primary of 85-99 Msun and a secondary of 28-32 Msun, in a 2.8-3.1 day orbit, its observed properties can be consistently explained. In this model, the Main Sequence primary transferred part of its envelope to the secondary and lost the rest in a wind; it ended its life as a ~16 Msun He star with a Fe-Ni core which collapsed to a black hole (with or without an accompanying supernova). The release of binding energy and, possibly, collapse asymmetries "kicked" the nascent black hole into an eccentric orbit. Wind accretion explains the X-Ray luminosity, while the black hole spin can be natal.Comment: Manuscript: 18 pages, 2 tables, 2 figure. Supplementary Information: 34 pages, 6 figures. Advance Online Publication (AOP) on http://www.nature.com/nature on October 20, 2010. To Appear in Nature on November 4, 201

The genetic profile of elite youth soccer players and its association with power and speed depends on maturity status

We investigated the association of multiple single nucleotide polymorphisms (SNPs) with athlete status and power/speed performance in elite male youth soccer players (ESP) and control participants (CON) at different stages of maturity. ESP (n = 535; aged 8–23 years) and CON (n = 151; aged 9–26 years) were genotyped for 10 SNPs and grouped according to years from predicted peak-height-velocity (PHV), i.e. pre- or post-PHV, to determine maturity status. Participants performed bilateral vertical countermovement jumps, bilateral horizontal-forward countermovement jumps, 20m sprints and modified 505-agility tests. Compared to CON, pre-PHV ESP demonstrated a higher ACTN3 (rs1815739) XX (‘endurance’) genotype frequency distribution, while post-PHV ESP revealed a higher frequency distribution of the PPARA (rs4253778) C-allele, AGT (rs699) GG genotype and NOS3 (rs2070744) T-allele (‘power’ genotypes/alleles). BDNF (rs6265) CC, COL5A1 (rs12722) CC and NOS3 TT homozygotes sprinted quicker than A-allele carriers, CT heterozygotes and CC homozygotes, respectively. COL2A1 (rs2070739) CC and AMPD1 (rs17602729) GG homozygotes sprinted faster than their respective minor allele carrier counterparts in CON and pre-PHV ESP, respectively. BDNF CC homozygotes jumped further than T-allele carriers, while ESP COL5A1 CC homozygotes jumped higher than TT homozygotes. To conclude, we have shown for the first time that pre- and post-PHV ESP have distinct genetic profiles, with pre-PHV ESP more suited for endurance, and post-PHV ESP for power and speed (the latter phenotypes being crucial attributes for post-PHV ESP). We have also demonstrated that power, acceleration and sprint performance were associated with five SNPs, both individually and in combination, possibly by influencing muscle size and neuromuscular activation

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development

Lower Use of Hospice by Cancer Patients who Live in Minority Versus White Areas

BACKGROUND: Although hospice care can alleviate suffering at the end of life for patients with cancer, it remains underutilized, particularly by African Americans and Hispanics. OBJECTIVE: To examine whether the racial composition of the census tract where an individual resides is associated with hospice use. DESIGN: Retrospective analysis of the Surveillance, Epidemiology, and End Results–Medicare file for individuals dying from breast, colorectal, lung, or prostate cancer (n = 70,669). MEASUREMENTS: Hospice use during the 12 months before death. RESULTS: Hospice was most commonly used by individuals who lived in areas with fewer African-American and Hispanic residents (47%), and was least commonly used by individuals who lived in areas with a high percentage of African-American and Hispanic residents (35%). Hispanics (odds ratio 0.51, 95% confidence interval 0.29–0.91) and African Americans (0.56, 0.44–0.71) were less likely to use hospice if they lived in a census tract with a high percentage of both African Americans and Hispanics than if they lived in a low minority tract. African Americans and whites were less likely to receive hospice care if they lived in a census tract with a high percentage of Hispanics than if they lived in a low minority area. CONCLUSIONS: Increasing hospice use may require interventions to improve the delivery of hospice care in minority communities

International evidence-based medicine survey of the veterinary profession: information sources used by veterinarians

Veterinarians are encouraged to use evidence to inform their practice, but it is unknown what resources (e.g. journals, electronic sources) are accessed by them globally. Understanding the key places veterinarians seek information can inform where new clinically relevant evidence should most effectively be placed. An international survey was conducted to gain understanding of how veterinary information is accessed by veterinarians worldwide. There were 2137 useable responses to the questionnaire from veterinarians in 78 countries. The majority of respondents (n = 1835/2137, 85.9%) undertook clinical work and worked in a high income country (n = 1576/1762, 89.4%). Respondents heard about the survey via national veterinary organisations or regulatory bodies (31.5%), online veterinary forums and websites (22.7%), regional, discipline-based or international veterinary organisations (22.7%) or by direct invitation from the researchers or via friends, colleagues or social media (7.6%). Clinicians and non-clinicians reportedly used journals most commonly (65.8%, n = 1207/1835; 75.6%, n = 216/286) followed by electronic resources (58.7%, n = 1077/1835; 55.9%, n = 160/286), respectively. Respondents listed a total of 518 journals and 567 electronic sources that they read. Differences in veterinarian preference for resources in developed, and developing countries, were found. The nominated journals most read were the Journal of the American Veterinary Medical Association (12.7% of nominations) for clinicians and the Veterinary Record (5.7%) for non-clinicians. The most accessed electronic resource reported was the Veterinary Information Network (25.6%) for clinicians and PubMed (7.4%) for non-clinicians. In conclusion, a wide array of journals and electronic resources appear to be accessed by veterinarians worldwide. Veterinary organisations appear to play an important role in global communication and outreach to veterinarians and consideration should be given to how these channels could be best utilised for effective dissemination of key research findings

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E-2

Liver disease is one of the leading causes of death worldwide1. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system2,3,4; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PGE2 in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2 bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (<30 mg/dl) and appears to have a role in modulating PGE2-mediated immune dysfunction. In vivo administration of human albumin solution to these patients significantly improved the plasma-induced impairment of macrophage proinflammatory cytokine production in vitro. Two mouse models of liver injury (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2, reduced circulating albumin concentrations and EP2-mediated immunosuppression. Treatment with COX inhibitors or albumin restored immune competence and survival following infection with group B Streptococcus. Taken together, human albumin solution infusions may be used to reduce circulating PGE2 levels, attenuating immune suppression and reducing the risk of infection in patients with acutely decompensated cirrhosis or ESLD

Staphylococcus aureus Host Cell Invasion and Virulence in Sepsis Is Facilitated by the Multiple Repeats within FnBPA

Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to α5β1 integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis

Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli

Bacterial chromosomes are organised as two replichores of opposite polarity that coincide with the replication arms from the ori to the ter region. Here, we investigated the effects of asymmetry in replichore organisation in Escherichia coli. We show that large chromosome inversions from the terminal junction of the replichores disturb the ongoing post-replicative events, resulting in inhibition of both cell division and cell elongation. This is accompanied by alterations of the segregation pattern of loci located at the inversion endpoints, particularly of the new replichore junction. None of these defects is suppressed by restoration of termination of replication opposite oriC, indicating that they are more likely due to the asymmetry of replichore polarity than to asymmetric replication. Strikingly, DNA translocation by FtsK, which processes the terminal junction of the replichores during cell division, becomes essential in inversion-carrying strains. Inactivation of the FtsK translocation activity leads to aberrant cell morphology, strongly suggesting that it controls membrane synthesis at the division septum. Our results reveal that FtsK mediates a reciprocal control between processing of the replichore polarity junction and cell division