The secreted proteins of Achlya hypogyna and Thraustotheca clavata identify the ancestral oomycete secretome and reveal gene acquisitions by horizontal gene transfer

This is the final version. Available on open access from Oxford University Press via the DOI in this recordSaprotrophic and parasitic microorganisms secrete proteins into the environment to breakdown macromolecules and obtain nutrients. The molecules secreted are collectively termed the "secretome" and the composition and function of this set of proteins varies depending on the ecology, life cycle, and environment of an organism. Beyond the function of nutrient acquisition, parasitic lineages must also secrete molecules to manipulate their host. Here, we use a combination of de novo genome and transcriptome sequencing and bioinformatic identification of signal peptides to identify the putative secreted proteome of two oomycetes, the facultative parasite Achlya hypogyna and free-living Thraustotheca clavata. By comparing the secretomes of these saprolegnialean oomycetes with that of eight other oomycetes, we were able to characterize the evolution of this protein set across the oomycete clade. These species span the last common ancestor of the two major oomycete families allowing us to identify the ancestral secretome. This putative ancestral secretome consists of at least 84 gene families. Only 11 of these gene families are conserved across all 10 secretomes analyzed and the two major branches in the oomycete radiation. Notably, we have identified expressed elicitin-like effector genes in the saprotrophic decomposer, T. clavata. Phylogenetic analyses show six novel horizontal gene transfers to the oomycete secretome from bacterial and fungal donor lineages, four of which are specific to the Saprolegnialeans. Comparisons between free-living and pathogenic taxa highlight the functional changes of oomycete secretomes associated with shifts in lifestyle.University of Rhode Island College of the Environment and Life SciencesU.S. Department of AgricultureNational Institutes of Health (NIH)National Science FoundationDivision of Biology and Medicine, Brown Universit

Identifying key controls on storm formation over the Lake Victoria Basin

The Lake Victoria region in East Africa is a hotspot for intense convective storms that are responsible for the deaths of thousands of fisherman each year. The processes responsible for the initiation, development and propagation of the storms are poorly understood and forecast skill is limited. Key processes for the lifecycle of two storms are investigated using Met Office Unified Model convection-permitting simulations with 1.5 km horizontal gridspacing. The two cases are analysed alongside a simulation of a period with no storms to assess the roles of the lake–land breeze, downslope mountain winds, prevailing large-scale winds and moisture availability. Whilst seasonal changes in large-scale moisture availability play a key role in storm development, the lake–land breeze circulation is a major control on the initiation location, timing and propagation of convection. In the dry season, opposing offshore winds form a bulge of moist air above the lake surface overnight that extends from the surface to ~1.5 km and may trigger storms in high CAPE/low CIN environments. Such a feature has not been explicitly observed or modelled in previous literature. Storms over land on the preceding day are shown to alter the local atmospheric moisture and circulation to promote storm formation over the lake. The variety of initiation processes and differing characteristics of just two storms analysed here show that the mean diurnal cycle over Lake Victoria alone is inadequate to fully understand storm formation. Knowledge of daily changes in local-scale moisture variability and circulations are key for skilful forecasts over the lake

Assessing Professionalism: A theoretical framework for defining clinical rotation assessment criteria

Although widely accepted as an important graduate competence, professionalism is a challenging outcome to define and assess. Clinical rotations provide an excellent opportunity to develop student professionalism through the use of experiential learning and effective feedback, but without appropriate theoretical frameworks, clinical teachers may find it difficult to identify appropriate learning outcomes. The adage “I know it when I see it” is unhelpful in providing feedback and guidance for student improvement, and criteria that are more specifically defined would help students direct their own development. This study sought first to identify how clinical faculty in one institution currently assess professionalism, using retrospective analysis of material obtained in undergraduate teaching and faculty development sessions. Subsequently, a faculty workshop was held in which a round-table type discussion sought to develop these ideas and identify how professionalism assessment could be improved. The output of this session was a theoretical framework for teaching and assessing professionalism, providing example assessment criteria and ideas for clinical teaching. This includes categories such as client and colleague interaction, respect and trust, recognition of limitations, and understanding of different professional identities. Each category includes detailed descriptions of the knowledge, skills, and behaviors expected of students in these areas. The criteria were determined by engaging faculty in the development of the framework, and therefore they should represent a focused development of criteria already used to assess professionalism, and not a novel and unfamiliar set of assessment guidelines. The faculty-led nature of this framework is expected to facilitate implementation in clinical teaching

Is four-dimensional CT angiography as effective as digital subtraction angiography in the detection of the underlying causes of intracerebral haemorrhage: a systematic review

To determine whether the sensitivity and specificity of four-dimensional CTA (4D-CTA) are equivalent to digital subtraction angiography (DSA) in the detection of underlying vascular abnormalities in patients with intracerebral haemorrhage (ICH). Methods A systematic review of studies comparing 4D-CTA with DSA in the detection of the underlying structural causes of ICH was performed on the literature published between 1998 and 2019. Results We identified a total of 237 articles from PubMed, SCOPUS and Web of Science using the following Medical Subject Headings (MeSH) terms: primary intracerebral haemorrhage, 4D-CTA, DSA, cerebral haemorrhage, angiography, digital subtraction, arteriovenous malformations, 4D, CTA, dynamic-CTA and time-resolved CTA. Following the removal of duplicate publications and articles failing to meet our inclusion criteria, there were four articles potentially viable for analysis. Therefore, there were not sufficient studies to provide a statistically meaningful meta-analysis. Conclusion The review of current literature has demonstrated that there are few published studies comparing 4D-CTA with DSA in spontaneous ICH, with only four suitable studies identified for potential analysis. However, due to the restricted number of patients and high sensitivity and specificity of 3 studies (100%), performing a meta-analysis was not meaningful. Qualitative analysis of the data concluded that 4D-CTA has the diagnostic potential to replace invasive DSA in certain cases with vascular abnormalities. However, further research studies directly comparing 4D-CTA with DSA using larger prospective patient cohorts are required to strengthen the evidence base.peer-reviewe

How the love of muscle can break a heart: Impact of anabolic androgenic steroids on skeletal muscle hypertrophy, metabolic and cardiovascular health.

It is estimated 6.4% of males and 1.6% of females globally use anabolic-androgenic steroids (AAS), mostly for appearance and performance enhancing reasons. In combination with resistance exercise, AAS use increases muscle protein synthesis resulting in skeletal muscle hypertrophy and increased performance. Primarily through binding to the androgen receptor, AAS exert their hypertrophic effects via genomic, non-genomic and anti-catabolic mechanisms. However, chronic AAS use also has a detrimental effect on metabolism ultimately increasing the risk of cardiovascular disease (CVD). Much research has focused on AAS effects on blood lipids and lipoproteins, with abnormal concentrations of these associated with insulin resistance, hypertension and increased visceral adipose tissue (VAT). This clustering of interconnected abnormalities is often referred as metabolic syndrome (MetS). Therefore, the aim of this review is to explore the impact of AAS use on mechanisms of muscle hypertrophy and markers of MetS. AAS use markedly decreases high-density lipoprotein cholesterol (HDL-C) and increases low-density lipoprotein cholesterol (LDL-C). Chronic AAS use also appears to cause higher fasting insulin levels and impaired glucose tolerance and possibly higher levels of VAT; however, research is currently lacking on the effects of AAS use on glucose metabolism. While cessation of AAS use can restore normal lipid levels, it may lead to withdrawal symptoms such as depression and hypogonadism that can increase CVD risk. Research is currently lacking on effective treatments for withdrawal symptoms and further long-term research is warranted on the effects of AAS use on metabolic health in males and females

REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis

Initial Results from the CHOOZ Long Baseline Reactor Neutrino Oscillation Experiment

Initial results are presented from CHOOZ, a long-baseline reactor-neutrino vacuum-oscillation experiment. Electron antineutrinos were detected by a liquid scintillation calorimeter located at a distance of about 1 km. The detector was constructed in a tunnel protected from cosmic rays by a 300 MWE rock overburden. This massive shielding strongly reduced potentially troublesome backgrounds due to cosmic-ray muons, leading to a background rate of about one event per day, more than an order of magnitude smaller than the observed neutrino signal. From the statistical agreement between detected and expected neutrino event rates, we find (at 90% confidence level) no evidence for neutrino oscillations in the electron antineutrino disappearance mode for the parameter region given approximately by deltam**2 > 0.9 10**(-3) eV**2 for maximum mixing and (sin(2 theta)**2) > 0.18 for large deltam**2.Comment: 13 pages, Latex, submitted to Physics Letters

Cellulolytic Bacteria in the foregut of the dromedary camel (Camelus dromedarius)

Foregut digesta from five feral dromedary camels were inoculated into three different enrichment media: cotton thread, filter paper, and neutral detergent fiber. A total of 283 16S rRNA gene sequences were assigned to 33 operational taxonomic units by using 99% species-level identity. LIBSHUFF revealed significant differences in the community composition across all three libraries