Volatile hydrocarbons inhibit methanogenic crude oil degradation

Methanogenic degradation of crude oil in subsurface sediments occurs slowly, but without the need for exogenous electron acceptors, is sustained for long periods and has enormous economic and environmental consequences. Here we show that volatile hydrocarbons are inhibitory to methanogenic oil biodegradation by comparing degradation of an artificially weathered crude oil with volatile hydrocarbons removed, with the same oil that was not weathered. Volatile hydrocarbons (nC5-nC10, methylcyclohexane, benzene, toluene, and xylenes) were quantified in the headspace of microcosms. Aliphatic (n-alkanes nC12-nC34) and aromatic hydrocarbons (4-methylbiphenyl, 3-methylbiphenyl, 2-methylnaphthalene, 1-methylnaphthalene) were quantified in the total hydrocarbon fraction extracted from the microcosms. 16S rRNA genes from key microorganisms known to play an important role in methanogenic alkane degradation (Smithella and Methanomicrobiales) were quantified by quantitative PCR. Methane production from degradation of weathered oil in microcosms was rapid (1.1 ± 0.1 μmol CH4/g sediment/day) with stoichiometric yields consistent with degradation of heavier n-alkanes (nC12-nC34). For non-weathered oil, degradation rates in microcosms were significantly lower (0.4 ± 0.3 μmol CH4/g sediment/day). This indicated that volatile hydrocarbons present in the non-weathered oil inhibit, but do not completely halt, methanogenic alkane biodegradation. These findings are significant with respect to rates of biodegradation of crude oils with abundant volatile hydrocarbons in anoxic, sulphate-depleted subsurface environments, such as contaminated marine sediments which have been entrained below the sulfate-reduction zone, as well as crude oil biodegradation in petroleum reservoirs and contaminated aquifers

B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis

<div><p>Recent success with B cell depletion therapies has revitalized efforts to understand the pathogenic role of B cells in Multiple Sclerosis (MS). Using the adoptive transfer system of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, we have previously shown that mice in which B cells are the only MHCII-expressing antigen presenting cell (APC) are susceptible to EAE. However, a reproducible delay in the day of onset of disease driven by exclusive B cell antigen presentation suggests that B cells require optimal conditions to function as APCs in EAE. In this study, we utilize an <i>in vivo</i> genetic system to conditionally and temporally regulate expression of MHCII to test the hypothesis that B cell APCs mediate attenuated and delayed neuroinflammatory T cell responses during EAE. Remarkably, induction of MHCII on B cells following the transfer of encephalitogenic CD4 T cells induced a rapid and robust form of EAE, while no change in the time to disease onset occurred for recipient mice in which MHCII is induced on a normal complement of APC subsets. Changes in CD4 T cell activation over time did not account for more rapid onset of EAE symptoms in this new B cell-mediated EAE model. Our system represents a novel model to study how the timing of pathogenic cognate interactions between lymphocytes facilitates the development of autoimmune attacks within the CNS.</p></div

A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol

The structures of two Dr adhesin (DraE) complexes with chloramphenicol derivatives, namely chloramphenicol succinate and bromamphenicol, have been solved. The structures reveal important functional groups for small-molecule binding and imply possible modifications to the molecule that would permit a more wide-ranging interaction without the toxic side effects associated with chloramphenicol

Revisiting telegony:Offspring inherit an acquired characteristic of their mother's previous mate

Newly discovered non-genetic mechanisms break the link between genes and inheritance, thereby also raising the possibility that previous mating partners could influence traits in offspring sired by subsequent males that mate with the same female (‘telegony’). In the fly Telostylinus angusticollis, males transmit their environmentally acquired condition via paternal effects on offspring body size. We manipulated male condition, and mated females to two males in high or low condition in a fully crossed design. Although the second male sired a large majority of offspring, offspring body size was influenced by the condition of the first male. This effect was not observed when females were exposed to the first male without mating, implicating semen-mediated effects rather than female differential allocation based on pre-mating assessment of male quality. Our results reveal a novel type of transgenerational effect with potential implications for the evolution of reproductive strategies

Talent identification and development: an academic review.

The Academic Review was commissioned to help evaluate Sportscotland's pilot Talent Identification and Development Programme which operated from early 2000 to the end of 2001. The Review highlights that the actual resources required for talent identification in the UK are concentrated on anthropometrical measures whereas the required resources should concentrate primarily on the psychological dimensions supported by the development of fundamental motor skills

Differences between murine arylamine N-acetyltransferase type 1 and human arylamine N-acetyltransferase type 2 defined by substrate specificity and inhibitor binding

Background: The mouse has three arylamine N-acetyltransferase genes, (MOUSE)Nat1, (MOUSE)Nat2 and (MOUSE)Nat3. These are believed to correspond to (HUMAN)NAT1, (HUMAN)NAT2 and NATP in humans. (MOUSE)Nat3 encodes an enzyme with poor activity and human NATP is a pseudogene. (MOUSE)Nat2 is orthologous to (HUMAN)NAT1 and their corresponding proteins are functionally similar, but the relationship between (MOUSE)Nat1 and (HUMAN)NAT2 is less clear-cut. Methods: To determine whether the (MOUSE)NAT1 and (HUMAN)NAT2 enzymes are functionally equivalent, we expressed and purified (MOUSE)NAT1*1 and analysed its substrate specificity using a panel of arylamines and hydrazines. To understand how specific residues contribute to substrate selectivity, three site-directed mutants of (MOUSE)NAT2*1 were prepared: these were (MOUSE)NAT2_F125S, (MOUSE)NAT2_R127G and (MOUSE)NAT2_R127L. All three exhibited diminished activity towards “(MOUSE)NAT2-specific” arylamines but were more active against hydrazines than (MOUSE)NAT1*1. The inhibitory and colorimetric properties of a selective naphthoquinone inhibitor of (HUMAN)NAT1 and (MOUSE)NAT2 were investigated. Results: Comparing (MOUSE)NAT1*1 with other mammalian NAT enzymes demonstrated that the substrate profiles of (MOUSE)NAT1 and (HUMAN)NAT2 are less similar than previously believed. Three key residues (F125, R127 and Y129) in (HUMAN)NAT1*4 and (MOUSE)NAT2*1 were required for enzyme inhibition and the associated colour change on naphthoquinone binding. In silico modelling of selective ligands into the appropriate NAT active sites further implicated these residues in substrate and inhibitor specificity in mouse and human NAT isoenzymes. Conclusions: Three non-catalytic residues within (HUMAN)NAT1*4 (F125, R127 and Y129) contribute both to substrate recognition and inhibitor binding by participating in distinctive intermolecular interactions and maintaining the steric conformation of the catalytic pocket. These active site residues contribute to the definition of substrate and inhibitor selectivity, an understanding of which is essential for facilitating the design of second generation (HUMAN)NAT1-selective inhibitors for diagnostic, prognostic and therapeutic purposes. In particular, since the expression of (HUMAN)NAT1 is related to the development and progression of oestrogen-receptor-positive breast cancer, these structure-based tools will facilitate the ongoing design of candidate compounds for use in (HUMAN)NAT1-positive breast tumours. </p

Prospective genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) associated with bloodstream infection, England, 1 October 2012 to 30 September 2013.

BackgroundMandatory reporting of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) has occurred in England for over 15years. Epidemiological information is recorded, but routine collection of isolates for characterisation has not been routinely undertaken. Ongoing developments in whole-genome sequencing (WGS) have demonstrated its value in outbreak investigations and for determining the spread of antimicrobial resistance and bacterial population structure. Benefits of adding genomics to routine epidemiological MRSA surveillance are unknown.AimTo determine feasibility and potential utility of adding genomics to epidemiological surveillance of MRSA.MethodsWe conducted an epidemiological and genomic survey of MRSA BSI in England over a 1-year period (1 October 2012--30 September 2013).ResultsDuring the study period, 903 cases of MRSA BSI were reported; 425 isolates were available for sequencing of which, 276 (65%) were clonal complex (CC) 22. Addition of 64 MRSA genomes from published outbreak investigations showed that the study genomes could provide context for outbreak isolates and supported cluster identification. Comparison to other MRSA genome collections demonstrated variation in clonal diversity achieved through different sampling strategies and identified potentially high-risk clones e.g. USA300 and local expansion of CC5 MRSA in South West England.ConclusionsWe demonstrate the potential utility of combined epidemiological and genomic MRSA BSI surveillance to determine the national population structure of MRSA, contextualise previous MRSA outbreaks, and detect potentially high-risk lineages. These findings support the integration of epidemiological and genomic surveillance for MRSA BSI as a step towards a comprehensive surveillance programme in England.This work was supported by grants from the UK Clinical Research Collaboration Translational Infection Research Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); and the Wellcome Trust (to Prof. Parkhill [Grant 098051], Prof. Peacock). MST is a Wellcome Trust Clinical PhD Fellow at the University of Cambridge. MET is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation, and by the National Institute for Health Research Cambridge Biomedical Research Centre. FC is supported by the Wellcome Trust (201344/Z/16/Z)

Posttraumatic Stress Disorder Biomarker — p11

Post-traumatic stress disorder (PTSD) is a chronic and disabling anxiety disorder associated with a traumatic event [1]. It is linked to increased risk of suicide and deficits in social functioning [2, 3]. Despite extensive study in psychiatry, the underlying mechanisms of PTSD are still poorly understood [4, 5]. Currently, the diagnosis for PTSD is based on clinical observation and symptom checklist [4, 6-8] and no laboratory blood-based tests. Although biomarker discovery for PTSD is not easy [8], a reliable biomarker would significantly impact the diagnosis and therapeutic monitoring of PTSD. Developing interventions to identify and treat PTSD requires objective approaches to determining the presence of PTSD [8]. Substantial data indicate several potential biomarkers for PTSD. Of these candidate markers, p11 (S100A10) has been studied in PTSD animal models [7] and in human subjects with PTSD [6]. We found that p11 is over-expressed in both animal models and post-mortem brains of subjects with PTSD [7]. Incorporating testing of p11, a novel biomarker for PTSD, into clinical practice, along with more subjective measures, such as participants’ medical history, mental status, duration of symptoms, and symptom checklist or self-report, would provide additional power to predict impending PTSD. In this chapter, we discuss the biomarker concept and the potential clinical utility of PTSD biomarkers. We further discuss the potential of p11 as a PTSD biomarker and as a tool that may enhance PTSD diagnosis and intervention in health care practice