TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

WIMP-nucleus scattering in chiral effective theory

We discuss long-distance QCD corrections to the WIMP-nucleon(s) interactions in the framework of chiral effective theory. For scalar-mediated WIMP-quark interactions, we calculate all the next-to-leading-order corrections to the WIMP-nucleus elastic cross-section, including two-nucleon amplitudes and recoil-energy dependent shifts to the single-nucleon scalar form factors. As a consequence, the scalar-mediated WIMP-nucleus cross-section cannot be parameterized in terms of just two quantities, namely the neutron and proton scalar form factors at zero momentum transfer, but additional parameters appear, depending on the short-distance WIMP-quark interaction. Moreover, multiplicative factorization of the cross-section into particle, nuclear and astro-particle parts is violated. In practice, while the new effects are of the natural size expected by chiral power counting, they become very important in those regions of parameter space where the leading order WIMP-nucleus amplitude is suppressed, including the so-called "isospin-violating dark matter" regime. In these regions of parameter space we find order-of-magnitude corrections to the total scattering rates and qualitative changes to the shape of recoil spectra.Comment: 23 pages, 6 figures, 1 tabl

Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites

Peer reviewedPublisher PD

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training

High-intensity interval training (HIT) has been proposed as a time-efficient alternative to traditional cardiorespiratory exercise training, but is very fatiguing. In this study, we investigated the effects of a reduced-exertion HIT (REHIT) exercise intervention on insulin sensitivity and aerobic capacity. Twenty-nine healthy but sedentary young men and women were randomly assigned to the REHIT intervention (men, n = 7; women, n = 8) or a control group (men, n = 6; women, n = 8). Subjects assigned to the control groups maintained their normal sedentary lifestyle, whilst subjects in the training groups completed three exercise sessions per week for 6 weeks. The 10-min exercise sessions consisted of low-intensity cycling (60 W) and one (first session) or two (all other sessions) brief ‘all-out’ sprints (10 s in week 1, 15 s in weeks 2–3 and 20 s in the final 3 weeks). Aerobic capacity ( V˙O2peakV˙O2peak ) and the glucose and insulin response to a 75-g glucose load (OGTT) were determined before and 3 days after the exercise program. Despite relatively low ratings of perceived exertion (RPE 13 ± 1), insulin sensitivity significantly increased by 28% in the male training group following the REHIT intervention (P < 0.05). V˙O2peakV˙O2peak increased in the male training (+15%) and female training (+12%) groups (P < 0.01). In conclusion we show that a novel, feasible exercise intervention can improve metabolic health and aerobic capacity. REHIT may offer a genuinely time-efficient alternative to HIT and conventional cardiorespiratory exercise training for improving risk factors of T2D