The compact, ∼1 kpc host galaxy of a quasar at a redshift of 7.1

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of the [C ii] fine-structure line and the underlying far-infrared (FIR) dust continuum emission in J1120+0641, the most distant quasar currently known ($z=7.1$). We also present observations targeting the CO(2–1), CO(7–6), and [C i] 369 μm lines in the same source obtained at the Very Large Array and Plateau de Bure Interferometer. We find a [C ii] line flux of ${F}_{[{\rm{C}}{\rm{II}}]}=1.11\pm 0.10$ Jy $\mathrm{km}\,{{\rm{s}}}^{-1}$ and a continuum flux density of ${S}_{227\mathrm{GHz}}=0.53\pm 0.04$ mJy beam−1, consistent with previous unresolved measurements. No other source is detected in continuum or [C ii] emission in the field covered by ALMA (~ 25''). At the resolution of our ALMA observations (0farcs23, or 1.2 kpc, a factor of ~70 smaller beam area compared to previous measurements), we find that the majority of the emission is very compact: a high fraction (~80%) of the total line and continuum flux is associated with a region 1–1.5 kpc in diameter. The remaining ~20% of the emission is distributed over a larger area with radius lesssim4 kpc. The [C ii] emission does not exhibit ordered motion on kiloparsec scales: applying the virial theorem yields an upper limit on the dynamical mass of the host galaxy of $(4.3\pm 0.9)\times {10}^{10}$ ${M}_{\odot }$, only ~20 × higher than the central black hole (BH). The other targeted lines (CO(2–1), CO(7–6), and [C i]) are not detected, but the limits of the line ratios with respect to the [C ii] emission imply that the heating in the quasar host is dominated by star formation, and not by the accreting BH. The star formation rate (SFR) implied by the FIR continuum is 105–340 ${M}_{\odot }\,{\mathrm{yr}}^{-1}$, with a resulting SFR surface density of ~100–350 ${M}_{\odot }\,{\mathrm{yr}}^{-1}$ kpc−2, well below the value for Eddington-accretion-limited star formation

The DDX6-4E-T interaction mediates translational repression and P-body assembly

This is the final version of the article. Available from the publisher via the DOI in this record.4E-Transporter binds eIF4E via its consensus sequence YXXXXLΦ, shared with eIF4G, and is a nucleocytoplasmic shuttling protein found enriched in P-(rocessing) bodies. 4E-T inhibits general protein synthesis by reducing available eIF4E levels. Recently, we showed that 4E-T bound to mRNA however represses its translation in an eIF4E-independent manner, and contributes to silencing of mRNAs targeted by miRNAs. Here, we address further the mechanism of translational repression by 4E-T by first identifying and delineating the interacting sites of its major partners by mass spectrometry and western blotting, including DDX6, UNR, unrip, PAT1B, LSM14A and CNOT4. Furthermore, we document novel binding between 4E-T partners including UNR-CNOT4 and unrip-LSM14A, altogether suggesting 4E-T nucleates a complex network of RNA-binding protein interactions. In functional assays, we demonstrate that joint deletion of two short conserved motifs that bind UNR and DDX6 relieves repression of 4E-T-bound mRNA, in part reliant on the 4E-T-DDX6-CNOT1 axis. We also show that the DDX6-4E-T interaction mediates miRNA-dependent translational repression and de novo P-body assembly, implying that translational repression and formation of new P-bodies are coupled processes. Altogether these findings considerably extend our understanding of the role of 4E-T in gene regulation, important in development and neurogenesis.BBSRC [BB/J00779X/1 to N.S.]; CNRS PICS (to D.W.); Agence Nationale pour la Recherche [ANR-14-CE09-0013-01ANR to D.W.]; Gates Cambridge Foundation (to A.K.); Fondation Wiener – Anspach of the Université Libre de Bruxelles and the Cambridge Newton Trust (C.V.). Funding for open access charge: BBSRC

Large perturbations in CO2 flux and subsequent chemosynthesis are induced in agricultural soil by the addition of elemental sulfur

The microbial contribution to soil organic matter has been shown to be much larger than previously thought and thus it plays a major role in carbon cycling. Among soil microorganisms, chemoautotrophs can fix CO2 without sunlight and can glean energy through the oxidation of reduced elements such as sulfur. Here we show that the addition of sulfur to soil results in an initial surge in production of CO2 through microbial respiration, followed by an order of magnitude increase in the capture of carbon from the atmosphere as elemental sulfur is oxidised to sulfate. Thiobacillus spp., take advantage of specific conditions to become the dominant chemoautotrophic group that consumes CO2. We discern the direct incorporation of atmospheric carbon into soil carbohydrate, protein and aliphatic compounds and differentiate these from existing biomass. These results suggest that chemoautotrophs can play a large role in carbon cycling and that this carbon is heavily influenced by land management practises

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

The C:N:P:S stoichiometry of soil organic matter

The formation and turnover of soil organic matter (SOM) includes the biogeochemical processing of the macronutrient elements nitrogen (N), phosphorus (P) and sulphur (S), which alters their stoichiometric relationships to carbon (C) and to each other. We sought patterns among soil organic C, N, P and S in data for c. 2000 globally distributed soil samples, covering all soil horizons. For non-peat soils, strong negative correlations (p < 0.001) were found between N:C, P:C and S:C ratios and % organic carbon (OC), showing that SOM of soils with low OC concentrations (high in mineral matter) is rich in N, P and S. The results can be described approximately with a simple mixing model in which nutrient-poor SOM (NPSOM) has N:C, P:C and S:C ratios of 0.039, 0.0011 and 0.0054, while nutrient-rich SOM (NRSOM) has corresponding ratios of 0.12, 0.016 and 0.016, so that P is especially enriched in NRSOM compared to NPSOM. The trends hold across a range of ecosystems, for topsoils, including O horizons, and subsoils, and across different soil classes. The major exception is that tropical soils tend to have low P:C ratios especially at low N:C. We suggest that NRSOM comprises compounds selected by their strong adsorption to mineral matter. The stoichiometric patterns established here offer a new quantitative framework for SOM classification and characterisation, and provide important constraints to dynamic soil and ecosystem models of carbon turnover and nutrient dynamics

Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness Publication

Copyright: © 2010 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Central corneal thickness (CCT), one of the most highly heritable human traits (h2 typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6×10−10. The locus on chromosome 16 was associated with CCT with p = 8.95×10−11. The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population

COVID-19 vaccine strategies for Aotearoa New Zealand: a mathematical modelling study

Background: COVID-19 elimination measures, including border closures have been applied in New Zealand. We have modelled the potential effect of vaccination programmes for opening borders. Methods: We used a deterministic age-stratified Susceptible, Exposed, Infectious, Recovered (SEIR) model. We minimised spread by varying the age-stratified vaccine allocation to find the minimum herd immunity requirements (the effective reproduction number Reff<1 with closed borders) under various vaccine effectiveness (VE) scenarios and R0 values. We ran two-year open-border simulations for two vaccine strategies: minimising Reff and targeting high-risk groups. Findings: Targeting of high-risk groups will result in lower hospitalisations and deaths in most scenarios. Reaching the herd immunity threshold (HIT) with a vaccine of 90% VE against disease and 80% VE against infection requires at least 86•5% total population uptake for R0=4•5 (with high vaccination coverage for 30-49-year-olds) and 98•1% uptake for R0=6. In a two-year open-border scenario with 10 overseas cases daily and 90% total population vaccine uptake (including 0-15 year olds) with the same vaccine, the strategy of targeting high-risk groups is close to achieving HIT, with an estimated 11,400 total hospitalisations (peak 324 active and 36 new daily cases in hospitals), and 1,030 total deaths. Interpretation: Targeting high-risk groups for vaccination will result in fewer hospitalisations and deaths with open borders compared to targeting reduced transmission. With a highly effective vaccine and a high total uptake, opening borders will result in increasing cases, hospitalisations, and deaths. Other public health and social measures will still be required as part of an effective pandemic response. Funding: This project was funded by the Health Research Council [20/1018]. Research in context.fals