Telesupervision Benefits for Placements: Allied Health Students’ and Supervisors’ Perceptions

Telesupervision (TS) uses Information and Communication Technology (ICT) for communication between university-based staff, clinical supervisors and students undertaking placements in the presence or absence of a clinical supervisor onsite. Despite examples of successful implementation (Carlin 2012, Chipchase et al. 2014, Dudding and Justice 2004, Hall 2013) there has been minimal uptake of TS in allied health. This study investigated students’ and clinical educators’ perceptions of the potential benefits and barriers of TS using readily accessible ICT during placements. During 2014-2015, telesupervision/telesupport was provided to a total of 54 Undergraduate and Graduate Entry Masters students from Speech Language Pathology (SLP), Occupational therapy (OT) and Physical therapy (PT) programs at one Australian and two Canadian universities and Exercise Physiology (EP) students at the Australian university. After receipt of TS, 39 students completed an online survey. Nine participating university-based clinical education coordinators (CECs) were interviewed about their experiences. Survey data were analysed using descriptive statistics and interview data were analysed using thematic analysis. Students valued regular TS contact/communication with their CEC to discuss challenges that arose during their placements. CECs believed students benefitted from the opportunities to discuss their placement experiences through TS sessions used for direct supervision and/or for complementing onsite supervision. Students used TS sessions to debrief and reflect on their placement experiences. CECs gained a better understanding of the students’ placement experiences. TS has the potential to develop greater connection between students and CECs and enhance student and supervisor experience of clinical education

IgD attenuates the IgM-induced anergy response in transitional and mature B cells

Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire

Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.The High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This study was supported by Wellcome Trust Strategic Award 082030 (CCG), Wellcome Trust Studentship 094446/Z/10/Z (KRB), the Oxford NIHR Biomedical Research Centre, and the MRC Human Immunology Unit (RJC). AJR and GL were supported by Wellcome Trust grant 090532/Z/ 09/Z, CCG and AE by a Major initiative Award from the Clive and Vera Ramaciotti Foundation, and AE by an NHMRC Career Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Earthworm activity and availability for meadow birds is restricted in intensively managed grasslands

Earthworms are an important prey for the endangered meadow birds of northwest Europe. Although intensive grassland management with high manure inputs generally promotes earthworm abundance, it may reduce the effective food availability for meadow birds through desiccation of the topsoil, which causes earthworms to remain deeper in the soil. We studied the response of Red Worm Lumbricus rubellus, a detritivore, and Grey Worm Aporrectodea caliginosa, a geophage, to soil moisture profiles in the field and under experimental conditions. Surfacing earthworms were counted weekly in eight intensively managed grasslands (treated with high inputs of slurry by slit injection) with variable groundwater tables in the Netherlands. At each count, soil penetration resistance, soil moisture tension and groundwater level were measured, while air temperature and humidity were obtained from a nearby weather station. The response to variation in the vertical distribution of soil moisture was also experimentally studied in the two earthworm species. In the field, earthworms’ surfacing activity at night was negatively associated with soil moisture tension and positively by relative air humidity. Surprisingly, there was no effect of groundwater level; an important management variable in meadow bird conservation. Under experimental conditions, both L. rubellus and A. caliginosa moved to deeper soil layers (&gt;20 cm) in drier soil moisture treatments, avoiding the upper layer when moisture levels dropped below 30%. Synthesis and applications. We propose that in intensively managed grasslands with slurry application, topsoil desiccation reduces earthworm availability for meadow birds. This can be counteracted by keeping soil moisture tensions of the top soil above −15 kPa. We suggest that the late raising of groundwater tables in spring and the disturbance of the soil by slit injection of slurry increase topsoil desiccation. This decreases earthworm availability when it matters most for breeding meadow birds. Meadow bird conservation will benefit from revised manure application strategies that promote earthworm activity near or at the soil surface.</p

B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8-dendritic cells require the intramembrane endopeptidase SPPL2A

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase-like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell-activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.R01 AI052127/AI/NIAID NIH HHS/United States U19 AI100627/AI/NIAID NIH HHS/United States Medical Research Council/United Kingdom Wellcome Trust/United Kingdo

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1Anaef, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1Anaef mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios+ PD-1+ CD4+ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1Anaef is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1Anaef naïve CD4+ T cells. CD44 expression, CD4+ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1AnaefMtorchino double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1Anaef T cell dysregulation

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios⁺ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1ᴬⁿᵃᵉᶠ, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1ᴬⁿᵃᵉᶠ mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios⁺ PD-1⁺ CD4⁺ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1ᴬⁿᵃᵉᶠ is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1ᴬⁿᵃᵉᶠ naïve CD4⁺ T cells. CD44 expression, CD4⁺ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1ᴬⁿᵃᵉᶠMtorᶜʰⁱⁿᵒ double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1ᴬⁿᵃᵉᶠ T cell dysregulation

CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10–driven MARCH1-mediated ubiquitination and degradation

By opposing IL-10–driven, MARCH1-mediated ubiquitination and degradation of MHC class II, CD83 may boost the immunogenicity of dendritic cells

A Europe-wide inventory of citizen-led energy action with data from 29 countries and over 10000 initiatives

Numerous case studies show that citizens engage in various ways in renewable and low carbon energy projects, thereby contributing to the sustainable energy transition. To date, however, a systematic and cross-country database on citizen-led initiatives and projects is lacking. By performing a major compilation and reviewing copious data sources from websites to official registries, we provide a Europe-wide inventory with over 10,000 initiatives and 16,000 production units in 29 countries, focusing on the past 20 years. Our data allow cross-country statistical analysis, supporting the elicitation of empirical insights capable of extending beyond the perspective of single case studies. Our data also align with ongoing efforts to implement two EU Directives that aim at strengthening the active role of citizens in the energy transition. While the focus of our data collection is on Europe, the data and methodology can contribute to the global analysis of citizen-led energy action