Evidence of neutral transcriptome evolution in plants

The transcriptome of an organism is its set of gene transcripts (mRNAs) at a defined spatial and temporal locus. Because gene expression is affected markedly by environmental and developmental perturbations, it is widely assumed that transcriptome divergence among taxa represents adaptive phenotypic selection. This assumption has been challenged by neutral theories which propose that stochastic processes drive transcriptome evolution. To test for evidence of neutral transcriptome evolution in plants, we quantified 18 494 gene transcripts in nonsenescent leaves of 14 taxa of Brassicaceae using robust cross-species transcriptomics which includes a two-step physical and in silicobased normalization procedure based on DNA similarity among taxa. Transcriptome divergence correlates positively with evolutionary distance between taxa and with variation in gene expression among samples. Results are similar for pseudogenes and chloroplast genes evolving at different rates. Remarkably, variation in transcript abundance among root-cell samples correlates positively with transcriptome divergence among root tissues and among taxa. Because neutral processes affect transcriptome evolution in plants, many differences in gene expression among or within taxa may be nonfunctional, reflecting ancestral plasticity and founder effects. Appropriate null models are required when comparing transcriptomes in space and time

Extracellular cell stress (heat shock) proteins - immune responses and disease: an overview

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory ‘danger signals’ for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease

Extravascular fibrinogen in the white matter of Alzheimer's disease and normal aged brains : implications for fibrinogen as a biomarker for Alzheimer's disease

The research was supported by the Alzheimer’s Society (grant numbers AS-PG-2013-011 and AS-JF-18-01). Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.The blood‐brain barrier (BBB) regulates cerebrovascular permeability and leakage of blood‐derived fibrinogen has been associated with cerebral arteriolosclerosis small vessel disease (SVD) and subsequent white matter lesions (WML). Furthermore, BBB‐dysfunction is associated with the pathogenesis of Alzheimer's disease (AD) with the presence of CSF plasma proteins suggested to be a potential biomarker of AD. We aimed to determine if extravascular fibrinogen in the white matter was associated with the development of AD hallmark pathologies, i.e., hyperphosphorylated tau (HPτ) and amyloid‐β (Aβ), SVD, cerebral amyloid angiopathy (CAA) and measures of white matter damage. Using human post‐mortem brains, parietal tissue from 20 AD and 22 non‐demented controls was quantitatively assessed for HPτ, Aβ, white matter damage severity, axonal density, demyelination and the burden of extravascular fibrinogen in both WML and normal appearing white matter (NAWM). SVD severity was determined by calculating sclerotic indices. WML‐ and NAWM fibrinogen burden was not significantly different between AD and controls nor was it associated with the burden of HPτ or Aβ pathology, or any measures of white matter damage. Increasing severity of SVD was associated with and a predictor (both p < 0.05) of both higher WML‐ and NAWM fibrinogen burden (both P<0.05) in controls only. In cases with minimal SVD NAWM fibrinogen burden was significantly higher in the AD cases (p<0.05). BBB dysfunction was present in both non‐demented and AD brains and was not associated with the burden of AD‐associated cortical pathologies. BBB dysfunction was strongly associated with SVD but only in the non‐demented controls. In cases with minimal SVD, BBB dysfunction was significantly worse in AD cases possibly indicating the influence of CAA. In conclusions, extravascular fibrinogen is not associated with AD hallmark pathologies but indicates SVD, suggesting that the presence of fibrinogen in the CSF is not a surrogate marker for AD pathology.PostprintPeer reviewe

Evidence for alignment of the rotation and velocity vectors in pulsars

We present strong observational evidence for a relationship between the direction of a pulsar's motion and its rotation axis. We show carefully calibrated polarization data for 25 pulsars, 20 of which display linearly polarized emission from the pulse longitude at closest approach to the magnetic pole. Such data allow determination of the position angle of the linear polarisation which in turn reflects the position angle of the rotation axis. Of these 20 pulsars, 10 show an offset between the velocity vector and the polarisation position angle which is either less than 10\degr or more than 80\degr, a fraction which is very unlikely by random chance. We believe that the bimodal nature of the distribution arises from the presence of orthogonal polarisation modes in the pulsar radio emission. In some cases this orthogonal ambiguity is resolved by observations at other wavelengths so that we conclude that the velocity vector and the rotation axis are aligned at birth. Strengthening the case is the fact that 4 of the 5 pulsars with ages less than 3 Myr show this relationship, including the Vela pulsar. We discuss the implications of these findings in the context of the Spruit & Phinney (1998)\nocite{sp98} model of pulsar birth-kicks. We point out that, contrary to claims in the literature, observations of double neutron star systems do not rule out aligned kick models and describe a possible observational test involving the double pulsar system.Comment: MNRAS, In Pres

Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

Quasi-monocrystalline silicon for low-noise end mirrors in cryogenic gravitational-wave detectors

Mirrors made of silicon have been proposed for use in future cryogenic gravitational-wave detectors, which will be significantly more sensitive than current room-temperature detectors. These mirrors are planned to have diameters of ≈50 cm and a mass of ≈200 kg. While single-crystalline float-zone silicon meets the requirements of low optical absorption and low mechanical loss, the production of this type of material is restricted to sizes much smaller than required. Here we present studies of silicon produced by directional solidification. This material can be grown as quasi-monocrystalline ingots in sizes larger than currently required. We present measurements of a low room-temperature and cryogenic mechanical loss comparable with float-zone silicon. While the optical absorption of our test sample is significantly higher than required, the low mechanical loss motivates research into further absorption reduction in the future. While it is unclear if material pure enough for the transmissive detector input mirrors can be achieved, an absorption level suitable for the highly reflective coated end mirrors seems realistic. Together with the potential to produce samples much larger than ≈50 cm, this material may be of great benefit for realizing silicon-based gravitational-wave detectors

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin