The interaction of ELKS with Ca2+ channel β subunits may contribute to active zone organization

The cytoskeletal matrix of the active zone (CAZ) and synaptic voltage-dependent calcium channels (VDCCs) are both required for the organization and regulation of synaptic vesicle release. Here we report a novel interaction between the CAZ protein family ELKS and VDCC β subunits. We found that two isoforms of ELKS (ELKS2 and ELKS1b) and two isoforms of VDCC β subunits (β1b and β4) co-immunoprecipitated. Using fluorescent immunohistochemistry, we observed colocalization between ELKS1b and VDCC β4 at synapses in the molecular layer of the cerebellum, suggesting a synaptic role for the interaction of these two proteins. Analysis of a P/Q-type VDCC knockout mouse (Cacna1a-/-) revealed that the localization of the VDCC β4 subunit to the molecular layer was disrupted, although ELKS1b protein localization was not affected. The results demonstrate that two isoforms of the ELKS family and two VDCC β subunits interact and suggest that their interaction may play a role in the organization of the active zone

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Implicit and explicit pedagogical practices related to sociocultural issues and social justice in physical education teacher education programs

Background: For many years, scholars in PETE have argued for the importance of educating pre-service teachers (PSTs) about equality (e.g., Evans 1990), sociocultural perspectives and issues (e.g., Cliff, Wright and Clarke, 2009; Author 2014) and critical pedagogy (e.g., Fernandez-Balboa 1997; Philpot 2015). Despite this advocacy, we would argue that there are significant differences in how faculty teach about sociocultural issues, and for, social justice. The pedagogical actions through which Physical Education Teacher Educators (PETEs) do this work is the focus of this paper. Purpose: We investigated the pedagogical approaches and strategies used by PETE faculty to address and educate PSTs about social justice and sociocultural issues related to gender, race, sexuality, (dis)ability, socioeconomic status and religion in their individual PETE programs. In this study, we draw on transformational pedagogy (Ukpokodu 2009; Ovens 2017) as a framework for theorizing the data. Through this study, we highlight the pedagogical practices espoused as those that engender transformative learning. Data collection and analysis: Data for this interpretive qualitative research study was collected primarily through in-depth semi-structured interviews with over 70 PETEs who work in 48 PETE programs across Australia, Canada, England, Ireland New Zealand, Sweden, and the United States. Furthermore, an informational survey was used to gather demographic data of the participants. The participants, all current PETEs, had a wide range of professional experiences, which included the length of time in the profession, the type of institution employed, educational backgrounds and courses taught. Data analysis was completed using the processes of content analysis and the constant comparative method (Corbin and Strauss 2008). Findings: Three major themes represent the findings. In the first theme, ‘Intentional and Explicit Pedagogies’ we provide descriptions of the approaches and strategies used by PETEs in this study that were planned in advance of the learning experiences. In the second theme, ‘Teachable Moments’ we provide examples of how PETEs utilized ‘teachable moments’ in implicit and explicit ways to educate PSTs about sociocultural issues. The third theme, ‘Resistance and Constraints’ captures the individual challenges PETE faculty faced within their courses if, and when, they teach for equity and social justice. The findings suggest that social justice struggles to find an explicit presence within many PETE programs and that educating PSTs about sociocultural issues and social justice is lacking in many PETE programs

SoDaH: the SOils DAta Harmonization database, an open-source synthesis of soil data from research networks, version 1.0

Data collected from research networks present opportunities to test theories and develop models about factors responsible for the long-term persistence and vulnerability of soil organic matter (SOM). Synthesizing datasets collected by different research networks presents opportunities to expand the ecological gradients and scientific breadth of information available for inquiry. Synthesizing these data is challenging, especially considering the legacy of soil data that have already been collected and an expansion of new network science initiatives. To facilitate this effort, here we present the SOils DAta Harmonization database (SoDaH; https://lter.github.io/som-website, last access: 22 December 2020), a flexible database designed to harmonize diverse SOM datasets from multiple research networks. SoDaH is built on several network science efforts in the United States, but the tools built for SoDaH aim to provide an open-access resource to facilitate synthesis of soil carbon data. Moreover, SoDaH allows for individual locations to contribute results from experimental manipulations, repeated measurements from long-term studies, and local- to regional-scale gradients across ecosystems or landscapes. Finally, we also provide data visualization and analysis tools that can be used to query and analyze the aggregated database. The SoDaH v1.0 dataset is archived and available at https://doi.org/10.6073/pasta/9733f6b6d2ffd12bf126dc36a763e0b4 (Wieder et al., 2020)

Positional Cloning of a Type 2 Diabetes Quantitative Trait Locus; Tomosyn-2, a Negative Regulator of Insulin Secretion

We previously mapped a type 2 diabetes (T2D) locus on chromosome 16 (Chr 16) in an F2 intercross from the BTBR T (+) tf (BTBR) Lepob/ob and C57BL/6 (B6) Lepob/ob mouse strains. Introgression of BTBR Chr 16 into B6 mice resulted in a consomic mouse with reduced fasting plasma insulin and elevated glucose levels. We derived a panel of sub-congenic mice and narrowed the diabetes susceptibility locus to a 1.6 Mb region. Introgression of this 1.6 Mb fragment of the BTBR Chr 16 into lean B6 mice (B6.16BT36–38) replicated the phenotypes of the consomic mice. Pancreatic islets from the B6.16BT36–38 mice were defective in the second phase of the insulin secretion, suggesting that the 1.6 Mb region encodes a regulator of insulin secretion. Within this region, syntaxin-binding protein 5-like (Stxbp5l) or tomosyn-2 was the only gene with an expression difference and a non-synonymous coding single nucleotide polymorphism (SNP) between the B6 and BTBR alleles. Overexpression of the b-tomosyn-2 isoform in the pancreatic β-cell line, INS1 (832/13), resulted in an inhibition of insulin secretion in response to 3 mM 8-bromo cAMP at 7 mM glucose. In vitro binding experiments showed that tomosyn-2 binds recombinant syntaxin-1A and syntaxin-4, key proteins that are involved in insulin secretion via formation of the SNARE complex. The B6 form of tomosyn-2 is more susceptible to proteasomal degradation than the BTBR form, establishing a functional role for the coding SNP in tomosyn-2. We conclude that tomosyn-2 is the major gene responsible for the T2D Chr 16 quantitative trait locus (QTL) we mapped in our mouse cross. Our findings suggest that tomosyn-2 is a key negative regulator of insulin secretion

The astrobiology primer: An outline of general knowledge - Version 1, 2006

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