Effecting clinical starting material quality and the impact to downstream processing

No Abstract

Urban grasslands support threatened water voles

Urbanisation is often linked with habitat loss and a reduction in species richness but some species may be able to adapt to urban environments. Water voles Arvicola amphibius, a rapidly declining species in the UK, have recently been recorded in isolated grassland habitats in Glasgow, Scotland’s largest city (human population 1.2 million). The aim of this study was to determine the distribution and habitat characteristics of water vole populations occupying these dry grasslands. Field work was undertaken from March to October 2014 in a 34 km2 study area located 3 km east of the city centre. Field sign transects recorded water vole presence in 21/65 (32%) and 19/62 (31%) surveyed sites in spring and autumn, respectively. Vole occupancy increased with distance from water and was greatest in parkland, followed by sites with rank vegetation and roadside habitats. Occupancy was lower where signs of predators were recorded but surprisingly occupancy was found to be greater in the most disturbed sites, perhaps linked to the fact that many of these sites were public parks containing suitable grassland. Sites occupied by water voles were classed as neutral grasslands with species composition dominated by two main species. The number of grassland sites occupied by water voles, especially within public areas suggests that careful management of these urban grassland habitats will benefit the conservation of this highly threatened species in the UK

Literature review of epidemiology studies on the association between exposure to particulate matter and human health outcomes

Airborne particles can come from a variety of sources and contain variable chemical constituents. Some particles are formed by natural processes, such as volcanoes, erosion, sea spray, and forest fires, while other are formed by anthropogenic processes, such as industrial- and motor vehicle-related combustion, road-related wear, and mining. In general, larger particles (those greater than 2.5 μm) are formed by mechanical processes, while those less than 2.5 μm are formed by combustion processes. The chemical composition of particles is highly influenced by the source: for combustion-related particles, factors such as temperature of combustion, fuel type, and presence of oxygen or other gases can also have a large impact on PM composition. These differences can often be observed at a regional level, such as the greater sulphate-composition of PM in regions that burn coal for electricity production (which contains sulphur) versus regions that do not. Most countries maintain air monitoring networks, and studies based on the resulting data are the most common basis for epidemiology studies on the health effects of PM. Data from these monitoring stations can be used to evaluate the relationship between community-level exposure to ambient particles and health outcomes (i.e., morbidity or mortality from various causes). Respiratory and cardiovascular outcomes are the most commonly assessed, although studies have also considered other related specific outcomes such as diabetes and congenital heart disease. The data on particle characteristics is usually not very detailed and most often includes some combination of PM2.5, PM10, sulphate, and NO2. Other descriptors that are less commonly found include particle number (ultrafine particles), metal components of PM, local traffic intensity, and EC/OC. Measures of association are usually reported per 10 μg/m3 or interquartile range increase in pollutant concentration. As the exposure data are taken from regional monitoring stations, the measurements are not representative of an individual's exposure. Particle size is an important descriptor for understanding where in the human respiratory system the particles will deposit: as a general rule, smaller particles penetrate to deeper regions of the lungs. Initial studies on the health effects of particulate matter focused on mass of the particles, including either all particles (often termed total suspended particulate or TSP) or PM10 (all particles with an aerodynamic diameter less than 10 μm). More recently, studies have considered both PM10 and PM2.5, with the latter corresponding more directly to combustion-related processes. UFPs are a dominant source of particles in terms of PNC, yet are negligible in terms of mass. Very few epidemiology studies have measured the effect of UFPs on health; however, the numbers of studies on this topic are increasing. In addition to size, chemical composition is of importance when understanding the toxicity of particles. Some studies consider the composition of particles in addition to mass; however this is not common, in part due the cost and labour involved in such analyses

Effects of a High Salt Diet on Blood Pressure Dipping and the Implications on Hypertension

High blood pressure, also known as hypertension, is a major risk factor for cardiovascular disease. Salt intake has been shown to have a significant impact on BP, but the mechanisms by which it influences the blood pressure dipping pattern, and 24-h blood pressure remains controversial. This literature review aims to both summarize the current evidence on high salt diet induced hypertension and discuss the epidemiological aspects including socioeconomic issues in the United States and abroad. Our review indicates that a high salt diet is associated with a blunted nocturnal blood pressure dipping pattern, which is characterized by a reduced decrease in blood pressure during the nighttime hours. The mechanisms by which high salt intake affects blood pressure dipping patterns are not fully understood, but it is suggested that it may be related to changes in the sympathetic nervous system. Further, we looked at the association between major blood pressure and circadian rhythm regulatory centers in the brain, including the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN) and nucleus tractus solitarius (nTS). We also discuss the underlying social and economic issues in the United States and around the world. In conclusion, the evidence suggests that a high salt diet is associated with a blunted, non-dipping, or reverse dipping blood pressure pattern, which has been shown to increase the risk of cardiovascular disease. Further research is needed to better understand the underlying mechanisms by which high salt intake influences changes within the central nervous system

Filamentary Dust Polarization and the Morphology of Neutral Hydrogen Structures

Filamentary structures in neutral hydrogen (H I) emission are well-aligned with the interstellar magnetic field, so H I emission morphology can be used to construct templates that strongly correlate with measurements of polarized thermal dust emission. We explore how the quantification of filament morphology affects this correlation. We introduce a new implementation of the Rolling Hough Transform (RHT) using spherical harmonic convolutions, which enables efficient quantification of filamentary structure on the sphere. We use this spherical RHT algorithm along with a Hessian-based method to construct H I-based polarization templates. We discuss improvements to each algorithm relative to similar implementations in the literature and compare their outputs. By exploring the parameter space of filament morphologies with the spherical RHT, we find that the most informative H I structures for modeling the magnetic field structure are the thinnest resolved filaments. For this reason, we find a $\sim10\%$ enhancement in the $B$-mode correlation with dust polarization with higher-resolution H I observations. We demonstrate that certain interstellar morphologies can produce parity-violating signatures, i.e., nonzero $TB$ and $EB$, even under the assumption that filaments are locally aligned with the magnetic field. Finally, we demonstrate that $B$ modes from interstellar dust filaments are mostly affected by the topology of the filaments with respect to one another and their relative polarized intensities, whereas $E$ modes are mostly sensitive to the shapes of individual filaments.Comment: 22 pages, 17 figure

Single-cell analysis reveals key differences between early-stage and late-stage systemic sclerosis skin across autoantibody subgroups

OBJECTIVES: The severity of skin involvement in diffuse cutaneous systemic sclerosis (dcSSc) depends on stage of disease and differs between anti-RNA-polymerase III (ARA) and anti-topoisomerase antibody (ATA) subsets. We have investigated cellular differences in well-characterised dcSSc patients compared with healthy controls (HCs). METHODS: We performed single-cell RNA sequencing on 4 mm skin biopsy samples from 12 patients with dcSSc and HCs (n=3) using droplet-based sequencing (10× genomics). Patients were well characterised by stage (>5 or <5 years disease duration) and autoantibody (ATA+ or ARA+). Analysis of whole skin cell subsets and fibroblast subpopulations across stage and ANA subgroup were used to interpret potential cellular differences anchored by these subgroups. RESULTS: Fifteen forearm skin biopsies were analysed. There was a clear separation of SSc samples, by disease, stage and antibody, for all cells and fibroblast subclusters. Further analysis revealed differing cell cluster gene expression profiles between ATA+ and ARA+ patients. Cell-to-cell interaction suggest differing interactions between early and late stages of disease and autoantibody. TGFβ response was mainly seen in fibroblasts and smooth muscle cells in early ATA+dcSSc skin samples, whereas in early ARA+dcSSc patient skin samples, the responding cells were endothelial, reflect broader differences between clinical phenotypes and distinct skin score trajectories across autoantibody subgroups of dcSSc. CONCLUSIONS: We have identified cellular differences between the two main autoantibody subsets in dcSSc (ARA+ and ATA+). These differences reinforce the importance of considering autoantibody and stage of disease in management and trial design in SSc

Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.

With the functional demonstration of a role in erythrocyte invasion by Plasmodium falciparum parasites, implications in the aetiology of common conditions that prevail in individuals of African origin, and a wealth of pharmacological knowledge, the stimulatory G protein (Gs) signal transduction pathway presents an exciting target for anti-malarial drug intervention. Having previously demonstrated a role for the G-alpha-s gene, GNAS, in severe malaria disease, we sought to identify other important components of the Gs pathway. Using meta-analysis across case-control and family trio (affected child and parental controls) studies of severe malaria from The Gambia and Malawi, we sought evidence of association in six Gs pathway candidate genes: adenosine receptor 2A (ADORA2A) and 2B (ADORA2B), beta-adrenergic receptor kinase 1 (ADRBK1), adenylyl cyclase 9 (ADCY9), G protein beta subunit 3 (GNB3), and regulator of G protein signalling 2 (RGS2). Our study amassed a total of 2278 cases and 2364 controls. Allele-based models of association were investigated in all genes, and genotype and haplotype-based models were investigated where significant allelic associations were identified. Although no significant associations were observed in the other genes, several were identified in ADORA2A. The most significant association was observed at the rs9624472 locus, where the G allele (approximately 20% frequency) appeared to confer enhanced risk to severe malaria [OR = 1.22 (1.09-1.37); P = 0.001]. Further investigation of the ADORA2A gene region is required to validate the associations identified here, and to identify and functionally characterize the responsible causal variant(s). Our results provide further evidence supporting a role of the Gs signal transduction pathway in the regulation of severe malaria, and request further exploration of this pathway in future studies

X-Linked Alport Dogs Demonstrate Mesangial Filopodial Invasion of the Capillary Tuft as an Early Event in Glomerular Damage

BACKGROUND: X-linked Alport syndrome (XLAS), caused by mutations in the type IV collagen COL4A5 gene, accounts for approximately 80% of human Alport syndrome. Dogs with XLAS have a similar clinical progression. Prior studies in autosomal recessive Alport mice demonstrated early mesangial cell invasion as the source of laminin 211 in the glomerular basement membrane (GBM), leading to proinflammatory signaling. The objective of this study was to verify this process in XLAS dogs. METHODS: XLAS dogs and WT littermates were monitored with serial clinicopathologic data and kidney biopsies. Biopsies were obtained at set milestones defined by the onset of microalbuminuria (MA), overt proteinuria, onset of azotemia, moderate azotemia, and euthanasia. Kidney biopsies were analyzed by histopathology, immunohistochemistry, and electron microscopy. RESULTS: XLAS dogs showed progressive decrease in renal function and progressive increase in interstitial fibrosis and glomerulosclerosis (based on light microscopy and immunostaining for fibronectin). The only identifiable structural abnormality at the time of microalbuminuria was ultrastructural evidence of mild segmental GBM multilamination, which was more extensive when overt proteinuria developed. Co-localization studies showed that mesangial laminin 211 and integrin α8β1 accumulated in the GBM at the onset of overt proteinuria and coincided with ultrastructural evidence of mild cellular interpositioning, consistent with invasion of the capillary loops by mesangial cell processes. CONCLUSION: In a large animal model, the induction of mesangial filopodial invasion of the glomerular capillary loop leading to the irregular deposition of laminin 211 is an early initiating event in Alport glomerular pathology

A sub-group of patients with hospital-acquired pneumonia do not require broad-spectrum gram-negative antimicrobial coverage

C.D.R. is supported by an Edinburgh Clinical Academic Track (ECAT)/Wellcome Trust PhD Training Fellowship for Clinicians award (214178/Z/18/Z).Among 200 patients developing hospital-acquired pneumonia (HAP) outside the intensive care unit, 61% were treated empirically without broad-spectrum Gram-negative coverage, with clinical cure in 69.7%. Lower disease severity markers (systemic inflammatory response syndrome, hypoxia, tachypnoea, neutrophilia) and the absence of diabetes mellitus and prior doxycycline treatment (but not the time to HAP onset) identified patients not requiring broad-spectrum Gram-negative coverage.Publisher PDFPeer reviewe

Targeted identification of genomic regions using TAGdb

Background: The introduction of second generation sequencing technology has enabled the cost effective sequencing of genomes and the identification of large numbers of genes and gene promoters. However, the assembly of DNA sequences to create a representation of the complete genome sequence remains costly, especially for the larger and more complex plant genomes. Results: We have developed an online database, TAGdb, that enables researchers to identify paired read sequences that share identity with a submitted query sequence. These tags can be used to design oligonucleotide primers for the PCR amplification of the region in the target genome. Conclusions: The ability to produce large numbers of paired read genome tags using second generation sequencing provides a cost effective method for the identification of genes and promoters in large, complex or orphan species without the need for whole genome assembly