Syndecan receptors: pericellular regulators in development and inflammatory disease.

The syndecans are the major family of transmembrane proteoglycans, usually bearing multiple heparan sulfate chains. They are present on virtually all nucleated cells of vertebrates and are also present in invertebrates, indicative of a long evolutionary history. Genetic models in both vertebrates and invertebrates have shown that syndecans link to the actin cytoskeleton and can fine-tune cell adhesion, migration, junction formation, polarity and differentiation. Although often associated as co-receptors with other classes of receptors (e.g. integrins, growth factor and morphogen receptors), syndecans can nonetheless signal to the cytoplasm in discrete ways. Syndecan expression levels are upregulated in development, tissue repair and an array of human diseases, which has led to the increased appreciation that they may be important in pathogenesis not only as diagnostic or prognostic agents, but also as potential targets. Here, their functions in development and inflammatory diseases are summarized, including their potential roles as conduits for viral pathogen entry into cells

Atomic data from the IRON Project. I. Electron-impact scattering of Fe17+ using <I>R</I>-matrix theory with intermediate coupling

We present results for electron-impact excitation of F-like Fe calculated using R-matrix theory where an intermediate-coupling frame transformation (ICFT) is used to obtain level-resolved collision strengths. Two such calculations are performed, the first expands the target using 2s2 2p5, 2s 2p6, 2s2 2p4 3l, 2s 2p5 3l, and 2p6 3l configurations while the second calculation includes the 2s2 2p4 4l, 2s 2p5 4l, and 2p6 4l configurations as well. The effect of the additional structure in the latter calculation on the n=3 resonances is explored and compared with previous calculations. We find strong resonant enhancement of the effective collision strengths to the 2s2 2p4 3s levels. A comparison with a Chandra X-ray observation of Capella shows that the n=4 R-matrix calculation leads to good agreement with observation</p

Substantial biases in ultra-short read data sets from high-throughput DNA sequencing

Novel sequencing technologies permit the rapid production of large sequence data sets. These technologies are likely to revolutionize genetics and biomedical research, but a thorough characterization of the ultra-short read output is necessary. We generated and analyzed two Illumina 1G ultra-short read data sets, i.e. 2.8 million 27mer reads from a Beta vulgaris genomic clone and 12.3 million 36mers from the Helicobacter acinonychis genome. We found that error rates range from 0.3% at the beginning of reads to 3.8% at the end of reads. Wrong base calls are frequently preceded by base G. Base substitution error frequencies vary by 10- to 11-fold, with A > C transversion being among the most frequent and C > G transversions among the least frequent substitution errors. Insertions and deletions of single bases occur at very low rates. When simulating re-sequencing we found a 20-fold sequencing coverage to be sufficient to compensate errors by correct reads. The read coverage of the sequenced regions is biased; the highest read density was found in intervals with elevated GC content. High Solexa quality scores are over-optimistic and low scores underestimate the data quality. Our results show different types of biases and ways to detect them. Such biases have implications on the use and interpretation of Solexa data, for de novo sequencing, re-sequencing, the identification of single nucleotide polymorphisms and DNA methylation sites, as well as for transcriptome analysis

Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England. [version 1; peer review: 2 approved]

Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions

Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort

Introduction People who are homeless often experience poor hospital discharge arrangements, reflecting ongoing care and housing needs. Specialist integrated homeless health and care provision (SIHHC) schemes have been developed and implemented to facilitate the safe and timely discharge of homeless patients from hospital. Our study aims to investigate the health outcomes of patients who were homeless and seen by a selection of SIHHC services. Methods and analysis Our study will employ a historical population-based cohort in England. We will examine health outcomes among three groups of adults: (1) homeless patients seen by specialist discharge schemes during their hospital admission; (2) homeless patients not seen by a specialist scheme and (3)admitted patients who live in deprived neighbourhoods and were not recorded as being homeless. Primary outcomes will be: time from discharge to next hospital inpatient admission; time from discharge to next accident and emergency attendance and 28-day emergency readmission. Outcome data will be generated through linkage to hospital admissions data (Hospital Episode Statistics) and mortality data for November 2013 to November 2016. Multivariable regression will be used to model the relationship between the study comparison groups and each of the outcomes. Ethics and dissemination Approval has been obtained from the National Health Service (NHS) Confidentiality Advisory Group (reference 16/CAG/0021) to undertake this work using unconsented identifiable data. Health Research Authority Research Ethics approval (REC 16/EE/0018) has been obtained in addition to local research and development approvals for data collection at NHS sites. We will feedback the results of our study to our advisory group of people who have lived experience of homelessness and seek their suggestions on ways to improve or take this work further for their benefit. We will disseminate our findings to SIHHC schemes through a series of regional workshops

A novel role for syndecan-3 in angiogenesis.

Syndecan-3 is one of the four members of the syndecan family of heparan sulphate proteoglycans and has been shown to interact with numerous growth factors via its heparan sulphate chains. The extracellular core proteins of syndecan-1,-2 and -4 all possess adhesion regulatory motifs and we hypothesized that syndecan-3 may also possess such characteristics. Here we show that a bacterially expressed GST fusion protein consisting of the entire mature syndecan-3 ectodomain has anti-angiogenic properties and acts via modulating endothelial cell migration. This work identifies syndecan-3 as a possible therapeutic target for anti-angiogenic therapy.This work was funded by Arthritis Research-UK (Grant No. 19207) and funds from the William Harvey Research Foundation both to JRW

The white-rot fungus, Phanerochaete chrysosporium, under combinatorial stress produces variable oil profiles following analysis of secondary metabolites

Aims: The effects of combinatorial stress on lipid production in Phanerochaete chrysosporium remains understudied. This species of white‐rot fungi was cultivated on solid‐state media whilst under variable levels of known abiotic and biotic stressors to establish the effect upon fungal oil profiles. Methods and Results: Environmental stressors induced upon the fungus included: temperature; nutrient limitation; and interspecies competition to assess impact upon oil profiles. Fatty acid type and concentration was determined using analytical methods of Gas Chromatography and Mass Spectrometry. Growth rate under stress was established using High Performance Liquid Chromatography with ergosterol as the biomarker. Fungi grown on solid‐state agar were able to simultaneously produce short and long‐chain fatty acids which appeared to be influenced by nutritional composition as well as temperature. Addition of nitrogen supplements increased the growth rate, but lipid dynamics remained unchanged. Introducing competition‐induced stress had significantly altered the production of certain fatty acids beyond that of the monoculture whilst under nutrient‐limiting conditions. Linoleic acid concentrations, for example, increased from an average of 885 ng/μl at monoculture towards 13820 ng/μl at co‐culture, following 7 days of incubation. Conclusions: Interspecies competition produced the most notable impact on lipid production for solid‐state media cultivated fungi whilst the addition of nitrogen supplementation presented growth and lipid accumulation to be uncorrelated. Combinatorial stress therefore influences the yield of overall lipid production as well as the number of intermediate fatty acids produced, deriving similar oil profiles to the composition of vegetable and fish oils. Significance and Impact of Study: Fungal secondary metabolism remains highly sensitive following combinatorial stress. The outcome impacts the research towards optimising fungal oil profiles for biomass and nutrition. Future investigations on fungal stress tolerance mechanisms need to address these environmental factors throughout the experimental design

Ionization state, excited populations and emission of impurities in dynamic finite density plasmas: I. The generalized collisional-radiative model for light elements

The paper presents an integrated view of the population structure and its role in establishing the ionization state of light elements in dynamic, finite density, laboratory and astrophysical plasmas. There are four main issues, the generalized collisional-radiative picture for metastables in dynamic plasmas with Maxwellian free electrons and its particularizing to light elements, the methods of bundling and projection for manipulating the population equations, the systematic production/use of state selective fundamental collision data in the metastable resolved picture to all levels for collisonal-radiative modelling and the delivery of appropriate derived coefficients for experiment analysis. The ions of carbon, oxygen and neon are used in illustration. The practical implementation of the methods described here is part of the ADAS Project

Self-reported health of Australian Defence Force personnel after use of anti-malarial drugs on deployment

The Departments of Defence and Veterans’ Affairs commissioned UQ School of Public Health to use data from health studies of the ADF deployments to East Timor and Bougainville to investigate anti-malarial drug use and health outcomes.\ua0This report presents the results of a descriptive analysis of self-reported anti-malarial drug use on deployment and self-reported health.Personnel who used the drug mefloquine reported more symptoms of psychological distress than those who used other anti-malarial drugs. However, the average differences observed were below the threshold of clinical significance and based on a small sample size in the mefloquine group.\ua0Fifty-seven participants (1.6% of the sample)\ua0mentioned the use of anti-malarial drugs as a concern in response to open-ended survey questions