Novel Inducers of the Envelope Stress Response BaeSR in Salmonella Typhimurium: BaeR Is Critically Required for Tungstate Waste Disposal

The RpoE and CpxR regulated envelope stress responses are extremely important for SalmonellaTyphimurium to cause infection in a range of hosts. Until now the role for BaeSR in both the Salmonella Typhimurium response to stress and its contribution to infection have not been fully elucidated. Here we demonstrate stationary phase growth, iron and sodium tungstate as novel inducers of the BaeRregulon, with BaeR critically required for Salmonella resistance to sodium tungstate. We show that functional overlap between the resistance nodulation-cell division (RND) multidrug transporters, MdtA, AcrD and AcrB exists for the waste disposal of tungstate from the cell. We also point to a role for enterobactinsiderophores in the protection of enteric organisms from tungstate, akin to the scenario in nitrogen fixing bacteria. Surprisingly, BaeR is the first envelope stress response pathway investigated in S. Typhimurium that is not required for murine typhoid in either ityS or ityR mouse backgrounds. BaeR is therefore either required for survival in larger mammals such as pigs or calves, an avian host such as chickens, or survival out with the host altogether where Salmonella and related enterics must survive in soil and water

Hard magnetic properties in nanoflake van der Waals Fe3GeTe2

Two dimensional (2D) van der Waals (vdW) materials have demonstrated fascinating optical, electrical and thickness-dependent characteristics. These have been explored by numerous authors but reports on magnetic properties and spintronic applications of 2D vdW materials are scarce by comparison. By performing anomalous Hall effect transport measurements, we have characterised the thickness dependent magnetic properties of single crystalline vdW Fe3GeTe2. The nanoflakes of this vdW metallic material exhibit a single hard magnetic phase with a near square-shaped magnetic loop, large coercivity (up to 550 mT at 2 K), a Curie temperature near 200 K and strong perpendicular magnetic anisotropy. Using criticality analysis, we confirmed the existence of magnetic coupling between vdW atomic layers and obtained an estimated coupling length of ~ 5 vdW layers in Fe3GeTe2. Furthermore, the hard magnetic behaviour of Fe3GeTe2 can be well described by a proposed model. The magnetic properties of Fe3GeTe2 highlight its potential for integration into vdW magnetic heterostructures, paving the way for spintronic research and applications based on these devices.Comment: Accepted by Nature Communication

Concepts of mental disorders in the United Kingdom : Similarities and differences between the lay public and psychiatrists

BACKGROUND: The lay public often conceptualise mental disorders in a different way to mental health professionals, and this can negatively impact on outcomes when in treatment. AIMS: This study explored which disorders the lay public are familiar with, which theoretical models they understand, which they endorse and how they compared to a sample of psychiatrists. METHODS: The Maudsley Attitude Questionnaire (MAQ), typically used to assess mental health professional's concepts of mental disorders, was adapted for use by a lay community sample (N = 160). The results were compared with a sample of psychiatrists (N = 76). RESULTS: The MAQ appeared to be accessible to the lay public, providing some interesting preliminary findings: in order, the lay sample reported having the best understanding of depression followed by generalised anxiety, schizophrenia and finally antisocial personality disorder. They best understood spiritualist, nihilist and social realist theoretical models of these disorders, but were most likely to endorse biological, behavioural and cognitive models. The lay public were significantly more likely to endorse some models for certain disorders suggesting a nuanced understanding of the cause and likely cure, of various disorders. Ratings often differed significantly from the sample of psychiatrists who were relatively steadfast in their endorsement of the biological model. CONCLUSION: The adapted MAQ appeared accessible to the lay sample. Results suggest that the lay public are generally aligned with evidence-driven concepts of common disorders, but may not always understand or agree with how mental health professionals conceptualise them. The possible causes of these differences, future avenues for research and the implications for more collaborative, patient-clinician conceptualisations are discussed.Peer reviewedFinal Accepted Versio

Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease

Key Points Regadenoson did not reduce iNKT cell activation to a prespecified level when administered to patients with SCD. Because iNKT cell activation was not reduced, the benefit of iNKT cell-based therapies in SCD cannot be determined.</jats:p

Change in net primary production and heterotrophic respiration: How much is necessary to sustain the terrestrial carbon sink?

In recent years, the chief approaches used to describe the terrestrial carbon sink have been either (1) inferential, based on changes in the carbon content of the atmosphere and other elements of the global carbon cycle, or (2) mechanistic, applying our knowledge of terrestrial ecology to ecosystem scale processes. In this study, the two approaches are integrated by determining the change in terrestrial properties necessary to match inferred change in terrestrial carbon storage. In addition, a useful mathematical framework is developed for understanding the important features of the terrestrial carbon sink. The Carnegie‐Ames‐Stanford Approach (CASA) biosphere model, a terrestrial carbon cycle model that uses a calibrated, semimechanistic net primary production model and a mechanistic plant and soil carbon turnover model, is employed to explore carbon turnover dynamics in terms of the specific features of terrestrial ecosystems that are most important for the potential development of a carbon sink and to determine the variation in net primary production (NPP) necessary to satisfy various carbon sink estimates. Given the existence of a stimulatory mechanism acting on terrestrial NPP, net ecosystem uptake is expected to be largest where NPP is high and the turnover of carbon through plants and the soil is slow. In addition, it was found that (1) long‐term, climate‐induced change in heterotrophic respiration is not as important in determining long‐term carbon exchange as is change in NPP and (2) the terrestrial carbon sink rate is determined not by the cumulative increase in production over some pre‐industrial baseline, but rather by the rate of increase in production over the industrial period

Functionalized micro-capillary film for the rapid at-line analysis of IgG aggregates in a cell culture bioreactor.

A micro-capillary film has been developed that offers the potential for an at-line analytical tool for rapid aggregate analysis during biopharmaceutical antibody production. A non-porous walled micro-capillary film (NMCF) with cation exchange functionality was demonstrated to act as a chromatography medium that could be operated with high linear fluid velocities and was highly resistant to blockage by entrained particulates, including cells. The NMCF containing 19 parallel microcapillaries was prepared using a melt extrusion process from poly(ethylene-vinyl alcohol) copolymer (EVOH). The NMCF-EVOH was modified to have cation-exchange functionality (NMCF-EVOH-SP) and shown to differentially bind monomer and aggregated species of IgG antibody directly from a bioreactor. The use of NMCF-EVOH-SP to quantify aggregate concentrations in monoclonal antibody preparations in less than 20 minutes was demonstrated.The authors would like to thank the EPSRC for the provision of a CASE Award. This study was sponsored by MedImmune, the global biologics R&D arm of AstraZeneca.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/19420862.2015.106536

Comparison of ecosystem processes in a woodland and prairie pond with different hydroperiods

Shallow lakes and ponds constitute a significant number of water bodies worldwide. Many are heterotrophic, indicating that they are likely net contributors to global carbon cycling. Climate change is likely to have important impacts on these waterbodies. In this study, we examined two small Minnesota ponds; a permanent woodland pond and a temporary prairie pond. The woodland pond had lower levels of phosphorus and phytoplankton than the prairie pond. Using the open water oxygen method, we found the prairie pond typically had a higher level of gross primary production (GPP) and respiration (R) than the woodland pond, although the differences between the ponds varied with season. Despite the differences in GPP and R between the ponds the net ecosystem production was similar with both being heterotrophic. Since abundant small ponds may play an important role in carbon cycling and are likely to undergo changes in temperature and hydroperiod associated with climate change, understanding pond metabolism is critical in predicting impacts and designing management schemes to mitigate changes

TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution

The utility of T‐cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination‐activating gene (RAG)‐1 or RAG‐2 knockouts is frequently used to generate mice with a monoclonal T‐cell repertoire. However, low level productive TCR rearrangement has been reported in RAG‐deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs. Our demonstration that functional nontransgenic TCRs are present in nonmanipulated mice has wide reaching ramifications worthy of critical consideration