Post-transcriptional regulation of the Type IIA sodium-phosphate cotransporter by parathyroid hormone.

The type IIa sodium-phosphate cotransporter (Npt2a) is expressed in the apical membrane of the renal proximal tubule and is responsible for the reabsorption of the majority of the filtered load of phosphate. Parathyroid hormone (PTH) is secreted by the parathyroid gland in response to a decrease in serum calcium or an increase in serum phosphorus, and acutely induces phosphaturia through the rapid stimulation of endocytosis of Npt2a and its subsequent lysosomal degradation. Chronic PTH stimulation leads to sustained phosphaturia, but the mechanisms for the chronic regulation of Npt2a by PTH remain unclear. We hypothesize that PTH decreases Npt2a mRNA levels as a mechanism for inducing chronic phosphaturia. We address this hypothesis within three specific aims. The first specific aim addresses the kinetics and mechanisms of the PTH-stimulated decrease in Npt2a mRNA expression. The second aim details the signaling pathways involved in PTH-mediated downregulation of Npt2a mRNA. Lastly, the third aim characterizes the PTH-responsive phosphoproteome of the proximal tubule, and how changes in the expression and phosphorylation of RNA-binding proteins may affect Npt2a mRNA stability. In Aim 1, we found that PTH decreases Npt2a steady-state mRNA levels with a 50% loss in 2.2h compared to 8.6h in the absence of PTH. This effect is post-transcriptional, and is dependent on both transcription and translation. In Aim 2, we determined that PTH destabilizes Npt2a mRNA through both PKA- and PKC-dependent mechanisms. The rapid initial decline in Npt2a mRNA levels corresponds to and appears to be dependent on early PTH-stimulated PKA activation. In contrast, PTH-stimulated PKC activation occurs more gradually over several hours and likely contributes to the latter phase of Npt2a mRNA destabilization. Finally, in Aim 3, we found that PTH alters the phosphorylation status of almost 1200 proteins in the proximal tubule, including 68 RNA-binding proteins (RBPs). Two of those RBPs, KHSRP and Roquin-2, bind to Npt2a mRNA, and their expression varies inversely with Npt2a mRNA levels. From these studies, we conclude that PTH-mediated Npt2a mRNA destabilization likely occurs through PKA- and PKC-dependent modulation of RBP expression and activity, and that KHSRP and Roquin-2 are potential mediators of the PTH response

Institutional and Student Transitions Into Enhanced Blended Learning

This presentation provides an overview of the ‘Transitions into blended learning’ project, which has focused on three areas: developing an institutional transition framework, researching student experiences, and identifying interventions to support effective transitions. The framework identified external drivers for blended learning, a set of considerations for institutions, and a set of processes to facilitate change involving three stakeholder groups at the heart of the model. The work included learner experience research with students newly engaged in blended learning. This work identified support needs around access (to technology and learning materials), attitudes (towards learning online) and attributes (skills) needed to engage autonomously in blended learning. The institution-wide Enhancement themes team identified a set of interventions or ‘anchor points’ to prevent the institution ‘drifting back’ into purely traditional approaches to learning and teaching. These included the recognition and promotion of good practice through case studies, development of an institutional e-learning framework, and an event to encourage staff and students to share good practice in blended learning. This three-year project was largely led by a PhD student (JA), working with the principal investigator (VHD) and the institutional representative (KG)

A quantitative evaluation of a regional Positive Behavioural Support workforce development approach

Background: Research suggests that providing staff with input in relation to Positive Behavioural Support (PBS) can have beneficial outcomes. Much of this research, however, fails to take account of systemic issues and does not include a control group. Method: We used a non-randomised, controlled group design to evaluate accredited PBS programmes, delivered as part of a systemic, regional and workforce development approach. We compared outcomes of those attending the programmes (n = 240) with a control group (n = 54), pre- and post-intervention and at 3-months follow-up. Results: The programme and its wider impact were rated positively. Significant intervention effects were found for staff practice and retention, but not for staff knowledge and attributions, or behaviours that challenge and quality of life of those being supported. Conclusions: The results are discussed in the context of the study limitations and restrictions resulting from the Covid-19 pandemic

Ionisation-induced star formation III: Effects of external triggering on the IMF in clusters

We report on Smoothed Particle Hydrodynamics (SPH) simulations of the impact on a turbulent $\sim2\times10^{3}$ M$_{\odot}$ star--forming molecular cloud of irradiation by an external source of ionizing photons. We find that the ionizing radiation has a significant effect on the gas morphology, but a less important role in triggering stars. The rate and morphology of star formation are largely governed by the structure in the gas generated by the turbulent velocity field, and feedback has no discernible effect on the stellar initial mass function. Although many young stars are to be found in dense gas located near an ionization front, most of these objects also form when feedback is absent. Ionization has a stronger effect in diffuse regions of the cloud by sweeping up low--density gas that would not otherwise form stars into gravitationally--unstable clumps. However, even in these regions, dynamical interactions between the stars rapidly erase the correlations between their positions and velocities and that of the ionization front.Comment: 12 pages, 16 figures (some downgraded to fit on astro-ph), accepted for publication in MNRA

Exploring the relative importance of factors that influence the job retention of social care staff working in intellectual disability services

We wanted to find out what would help care staff to stay in their jobs. The most important thing for them was getting on well with the person they supported. The next most important thing was their pay. These results can be used to find ways to help staff stay in their jobs. This is important to make sure that people with a learning disability get good support. Abstract: Background: High staff turnover presents a challenge to the provision of good quality community-based support to people with an intellectual disability. While recent research has identified factors that are thought to be important for staff retention, their relative importance to social care staff is unknown. The aim of this study was to address this gap. Methods: 205 social care staff who worked in intellectual disability services completed an online questionnaire that asked them to: rank factors that had been previously identified as influencing staff retention in order of importance; identify the extent to which their most important factor was met by their organisation (fulfilment score); and rate their recent job-seeking intentions. Findings: The most important factor overall was the relationship of the staff member with the person they supported. This was also identified as the most important factor by the most participants, followed by pay. All of the factors, with the exception of “benefits” (such as pensions), were rated by at least one person as the most important factor. A significant negative relationship was found between fulfilment score and job-seeking score; that is, the lower the former, the more the person agreed that they had been seeking a new job. Conclusion: The results suggest that interventions to improve staff retention should take account of differences in staff views about which work-related factors are most important to them; use multi-component approaches where possible; prioritise staff pay; and help ensure that staff relationships with those they support are positive and fulfilling

Service provision in Scotland for people with an intellectual disability who have, or are at risk of developing, dementia

This research aimed to identify current national provision by health services in Scotland in relation to proactive screening and reactive assessment for people with an intellectual disability in Scotland who have, or are at risk of developing, dementia. Staff from 12 intellectual disability services, representing the 11 health board areas in Scotland, completed an online questionnaire which asked about proactive screening and reactive assessment for people with intellectual disability who had, or were at risk of developing, dementia as well as suggested areas for improvement. All of the areas provided services for people with intellectual disability who have, or are at risk of developing, dementia, but differed as to whether this was reactive, proactive or both. Nine services offered intervention following diagnosis. The most common elements used across both proactive screening and reactive assessment were conducting a health check, using a general dementia questionnaire designed for people with an intellectual disability and direct assessment with the person. Clinical psychology and community learning disability nurses were the professions most likely to be involved routinely in both proactive screening and reactive assessments. The psychometric properties of the most commonly used assessments of cognitive and behavioural functioning were mixed. The areas of improvement suggested by practitioners mainly related to ways of improving existing pathways. This research represents the first step in providing an overview of service provision in Scotland. There was some inconsistency in relation to the general and specific components which were involved in proactive screening and reactive assessment. Implications for service provision are discussed