Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm

Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for basement membrane deposition and has essential roles in tissue morphogenesis and patterning. Yet, the mechanisms controlling Laminin-111 expression are poorly understood. We generated a zebrafish transgenic reporter line that reproduces faithfully the expression pattern of lama1, the gene encoding Laminin α1, and we used this reporter line to investigate lama1 transcriptional regulation. Our findings established that lama1 expression is controlled by intronic enhancers, including an enhancer directing expression in the paraxial mesoderm, anterior spinal cord and hindbrain, located in intron 1. We show that Hedgehog signalling is necessary and sufficient for lama1 transcription in the paraxial mesoderm and identify putative Gli/Zic binding sites that may mediate this control. These findings uncover a conserved role for Hedgehog signalling in the control of basement membrane assembly via its transcriptional regulation of lama1, and provide a mechanism to coordinate muscle cell fate specification in the zebrafish embryo

Burden of disease and circulating serotypes of rotavirus infection in sub-Saharan Africa: systematic review and meta-analysis.

Two new rotavirus vaccines have recently been licensed in many countries. However, their efficacy has only been shown against certain serotypes commonly circulating in Europe, North America, and Latin America, but thought to be globally important. To assess the potential impact of these vaccines in sub-Saharan Africa, where rotavirus mortality is high, knowledge of prevalent types is essential because an effective rotavirus vaccine is needed to protect against prevailing serotypes in the community. We did two systematic reviews and two meta-analyses of the most recent published data on the burden of rotavirus disease in children aged under 5 years and rotavirus serotypes circulating in countries in sub-Saharan Africa. Eligible studies were selected from PubMed/Medline, Cochrane Library, EmBase, LILACS, Academic Search Premier, Biological Abstracts, ISI Web of Science, and the African Index Medicus. Depending on the heterogeneity, DerSimonian-Laird random-effects or fixed-effects models were used for meta-analyses. Geographical variability in rotavirus burden within countries in sub-Saharan Africa is substantial, and most countries lack information on rotavirus epidemiology. We estimated that annual mortality for this region was 243.3 (95% CI 187.6-301.7) deaths per 100,000 under 5 years (ie, a total of 300,000 children die of rotavirus infection in this region each year). The most common G type detected was G1 (34.9%), followed by G2 (9.1%), and G3 (8.6%). The most common P types detected were P[8] (35.5%) and P[6] (27.5%). Accurate information should be collected from surveillance based on standardised methods in these countries to obtain comparable data on the burden of disease and the circulating strains to assess the potential impact of vaccine introduction

New zebrafish models of neurodegeneration

In modern biomedicine, the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on the society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here, we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited. We shall do so by citing and commenting on recent breakthroughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms

Melanin concentrating hormone in peripheral circulation in the human

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role

Social and asocial learning in zebrafish are encoded by a shared brain network that is differentially modulated by local activation

Social and asocial learning in zebrafish are encoded by a shared brain network that is differentially modulated by local activatio

The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)

Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention. Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff. Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision. Conclusions: We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes

Global Decay Chain Vertex Fitting at B-Factories

We present a particle vertex fitting method designed for B factories. The presented method uses a Kalman Filter to solve a least squares estimate to globally fit decay chains, as opposed to traditional methods that fit each vertex at a time. It allows for the extraction of particle momenta, energies, vertex positions and flight lengths, as well as the uncertainty estimates of these quantities. Furthermore, it allows for the precise extraction of vertex parameters in complex decay chains containing neutral final state particles, such as ${\gamma}$ or $K^0_L$ , which cannot properly be tracked due to limited spatial resolution of longitudinally segmented single-layer crystal calorimeters like the Belle II ECL. The presented technique can be used to suppress combinatorial background and improve resolutions on measured parameters. We present studies using Monte Carlo simulations of collisions in the Belle II experiment, where modes with neutrals are crucial to the physics analysis program

Rapid retreat of permafrost coastline observed with aerial drone photogrammetry

Permafrost landscapes are changing around the Arctic in response to climate warming, with coastal erosion being one of the most prominent and hazardous features. Using drone platforms, satellite images, and historic aerial photographs, we observed the rapid retreat of a permafrost coastline on Qikiqtaruk – Herschel Island, Yukon Territory, in the Canadian Beaufort Sea. This coastline is adjacent to a gravel spit accommodating several culturally significant sites and is the logistical base for the Qikiqtaruk – Herschel Island Territorial Park operations. In this study we sought to (i) assess short-term coastal erosion dynamics over fine temporal resolution, (ii) evaluate short-term shoreline change in the context of long-term observations, and (iii) demonstrate the potential of low-cost lightweight unmanned aerial vehicles (“drones”) to inform coastline studies and management decisions. We resurveyed a 500&thinsp;m permafrost coastal reach at high temporal frequency (seven surveys over 40&thinsp;d in 2017). Intra-seasonal shoreline changes were related to meteorological and oceanographic variables to understand controls on intra-seasonal erosion patterns. To put our short-term observations into historical context, we combined our analysis of shoreline positions in 2016 and 2017 with historical observations from 1952, 1970, 2000, and 2011. In just the summer of 2017, we observed coastal retreat of 14.5&thinsp;m, more than 6 times faster than the long-term average rate of 2.2±0.1&thinsp;m&thinsp;a−1 (1952–2017). Coastline retreat rates exceeded 1.0±0.1&thinsp;m&thinsp;d−1 over a single 4&thinsp;d period. Over 40&thinsp;d, we estimated removal of ca. 0.96&thinsp;m3&thinsp;m−1&thinsp;d−1. These findings highlight the episodic nature of shoreline change and the important role of storm events, which are poorly understood along permafrost coastlines. We found drone surveys combined with image-based modelling yield fine spatial resolution and accurately geolocated observations that are highly suitable to observe intra-seasonal erosion dynamics in rapidly changing Arctic landscapes.</p

Allometric Relationships for Predicting Aboveground Biomass and Sapwood Area of Oneseed Juniper (Juniperus monosperma) Trees

This is the final version. Available from Frontiers Media via the DOI in this record. Across the semi-arid ecosystems of the southwestern USA, there has been widespread encroachment of woody shrubs and trees including Juniperus species into former grasslands. Quantifying vegetation biomass in such ecosystems is important because semi-arid ecosystems are thought to play an important role in the global land carbon (C) sink, and changes in plant biomass also have implications for primary consumers and potential bioenergy feedstock. Oneseed Juniper (J. monosperma) is common in desert grasslands and pinyon-juniper rangelands across the intermountain region of southwestern North America; however, there is limited information about the aboveground biomass (AGB) and sapwood area (SWA) for this species, causing uncertainties in estimates of C stock and transpiration fluxes. In this study, we report on canopy area, stem diameter, maximum height and biomass measurements from J. monosperma trees sampled from central New Mexico. Dry biomass ranged between 0.4 kg and 625 kg, and cross-sectional sapwood area was measured on n=200 stems using image analysis. We found a strong linear relationship between canopy area and AGB (r2 = 0.96), with a similar slope to that observed in other juniper species, suggesting that this readily measured attribute is well suited for upscaling studies. There was a 9% bias between different approaches to measuring canopy area, indicating care should be taken to account for these differences to avoid systematic biases. We found equivalent stem diameter (ESD) was a strong predictor of biomass, but that existing allometric models under-predicted biomass in larger trees. We found sapwood area could be predicted from individual stem diameter with a power relationship, and that tree-level SWA should be estimated by summing the SWA predictions from individual stems rather than ESD. Our improved allometric models for J. monosperma support more accurate and robust measurements of C storage and transpiration fluxes in Juniperus-dominated ecosystems.Natural Environment Research Council (NERC)U.S. National Science Foundatio