N1-Src kinase is required for primary neurogenesis in Xenopus tropicalis

The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine kinase is conserved through vertebrate evolution, suggesting an important role in complex nervous systems. Alternative splicing involving a N1-Src specific microexon leads to a five or six amino acid insertion into the SH3 domain of Src. A prevailing model suggests that N1-Src regulates neuronal differentiation via cytoskeletal dynamics in the growth cone. Here we have investigated the role of n1-src in the early development of the amphibian Xenopus tropicalis, and find that n1-src expression is regulated in embryogenesis, with highest levels detected during the phases of primary and secondary neurogenesis. In situ hybridisation analysis, using locked nucleic acid (LNA) oligo probes complementary to the n1-src microexon indicate that n1-src expression is highly enriched in the open neural plate during neurula stages and in the neural tissue of adult frogs. Given the n1-src expression pattern, we investigated a possible role for n1-src in neurogenesis. Using splice site-specific antisense morpholino oligos, we are able to inhibit n1-src splicing, whilst preserving c-src expression. Differentiation of neurons in the primary nervous system is reduced in n1-src knockdown embryos, accompanied by a severely impaired touch response in later development. These data reveal an essential role for n1-src in amphibian neural development and suggest that alternative splicing of C-Src in the developing vertebrate nervous system evolved to regulate neurogenesis

N1-Src kinase is required for primary neurogenesis in Xenopus tropicalis

The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine kinase is conserved through vertebrate evolution, suggesting an important role in complex nervous systems. Alternative splicing involving a N1-Src specific microexon leads to a five or six amino acid insertion into the SH3 domain of Src. A prevailing model suggests that N1-Src regulates neuronal differentiation via cytoskeletal dynamics in the growth cone. Here we have investigated the role of n1-src in the early development of the amphibian Xenopus tropicalis, and find that n1-src expression is regulated in embryogenesis, with highest levels detected during the phases of primary and secondary neurogenesis. In situ hybridisation analysis, using locked nucleic acid (LNA) oligo probes complementary to the n1-src microexon indicate that n1-src expression is highly enriched in the open neural plate during neurula stages and in the neural tissue of adult frogs. Given the n1-src expression pattern, we investigated a possible role for n1-src in neurogenesis. Using splice site-specific antisense morpholino oligos, we are able to inhibit n1-src splicing, whilst preserving c-src expression. Differentiation of neurons in the primary nervous system is reduced in n1-src knockdown embryos, accompanied by a severely impaired touch response in later development. These data reveal an essential role for n1-src in amphibian neural development and suggest that alternative splicing of C-Src in the developing vertebrate nervous system evolved to regulate neurogenesis

Social Isolation and Cognitive Function in Later Life: A Systematic Review and Meta-Analysis.

BACKGROUND: There is some evidence to suggest that social isolation may be associated with poor cognitive function in later life. However, findings are inconsistent and there is wide variation in the measures used to assess social isolation. OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the association between social isolation and cognitive function in later life. METHODS: A search for longitudinal studies assessing the relationship between aspects of social isolation (including social activity and social networks) and cognitive function (including global measures of cognition, memory, and executive function) was conducted in PsycInfo, CINAHL, PubMed, and AgeLine. A random effects meta-analysis was conducted to assess the overall association between measures of social isolation and cognitive function. Sub-analyses investigated the association between different aspects of social isolation and each of the measures of cognitive function. RESULTS: Sixty-five articles were identified by the systematic review and 51 articles were included in the meta-analysis. Low levels of social isolation characterized by high engagement in social activity and large social networks were associated with better late-life cognitive function (r = 0.054, 95% CI: 0.043, 0.065). Sub-analyses suggested that the association between social isolation and measures of global cognitive function, memory, and executive function were similar and there was no difference according to gender or number of years follow-up. CONCLUSIONS: Aspects of social isolation are associated with cognitive function in later life. There is wide variation in approaches to measuring social activity and social networks across studies which may contribute to inconsistencies in reported findings.We are grateful to the Alzheimer’s Society for funding a PhD scholarship for Isobel Evans to complete this work through the following grant: Transdisciplinary training for dementia research in CFAS (The Alzheimer’s Society CFAS Doctoral Training Centre). 2015–2018. AS-DTC-2014-027

Exploring self-harm risk vulnerabilities in autism using the ‘thinking patterns profiling model’

From Springer Nature via Jisc Publications RouterHistory: received 2022-11-21, registration 2023-02-23, accepted 2023-02-23, epub 2023-03-20, online 2023-03-20, collection 2023-12Acknowledgements: This project was conducted through the Structured Operational Research and Training Initiative (SORT IT), a global partnership led by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization. The training is based on a course developed jointly by the International Union Against Tuberculosis and Lung Disease (The Union) and Medécins sans Frontières. This specific SORT IT program was run by Cheshire and Wirral Partnership (CWP) NHS Foundation Trust as part of routine work. Mentorship and the coordination/facilitation of these SORT IT workshops were provided through the CWP NHS Foundation Trust; The Centre for Operational Research, The Union, Paris, France; The Institute of Medicine, University of Chester, UK; and College of Life and Environmental Science, University of Exeter. The authors would like to acknowledge the families who attended the autism diagnostic assessment profiling service, and to thank the experts by experience who shared their insight, contributed to interpretation of the study findings, and reviewed final versions of the manuscript. Experts by experience included Josef de la Moitie and Kevin Carrell who were happy to be named. The authors would also like to thank Professor Taj Nathan (Director of Research and Effectiveness), Dr Fiona Pender (Strategic Director), Anne Casey (Head of Clinical Services), Dr Ian Davidson (Consultant Psychiatrist and Royal College of Psychiatrists Autism Champion), and Heather Pearce (Advanced Specialist Speech and Language Therapist) all at Cheshire and Wirral Partnership NHS Foundation Trust. Finally, thank you to David Tollerfield for permission to use the ‘Thinking Patterns Profiling Model’ digital innovations as part of the diagnostic assessment profiling service.Publication status: PublishedBackground: Autism has been linked to higher rates of self-harm. Research is yet to establish the reason for the association between autism and self-harm as a distress response. Methods: Using the ‘thinking patterns profiling model’, this study explored characteristics associated with self-harm risk in 100 autistic young people. Secondary analysis of routinely collected clinical data was conducted using odds ratios and t-tests. Results: We found the prevalence of reported self-harm risk was 48%. Young people with reported self-harm risks had significantly lower regulation skills (p ≤ 0.01) and lower social flexibility skills (p ≤ 0.01) compared to those without reported self-harm risk. For those described as impulsive, mean scores on the following skills were significantly lower: perspective-taking skills (p ≤ 0.01), flexible thinking for creative problem-solving (p ≤ 0.05) and sensory tolerating (p ≤ 0.05). There was no relationship between reported self-harm risk and adverse childhood experiences. Conclusions: These findings suggest that profiling tools such as ‘Thinking Patterns Profiling Model’ can be used to explore unique patterns of vulnerability and resilience related to self-harm risk in autism. The findings suggest that autistic thinking patterns might interplay with other factors (e.g. impulsivity). Patterns are based on each person’s profile across four core skill-sets: regulation, flexible thinking, sensory coherence, and social perspective-taking. These findings motivate a person-centred and profile-informed approach to planning support and adjustments. Further studies are needed to confirm the ways in which mechanisms typically involved in self-harm risk, may interact with core cognitive and affective differences found in autism

Adapting student practice placements in response to COVID-19: 'Get there together' a digital stories project for people living with dementia

The impact of COVID-19 has been harshly felt by occupational therapists in practice and students requiring practice education placements. A collaboration between Aneurin Bevan University Health Board (ABUHB) and Cardiff University enabled 10 undergraduate students to undertake their final placement by participating in a Digital Stories Project. This placement was innovatively designed to allow students to meet their learning objectives remotely, reducing clinical days in adherence to social distancing measures. The ‘Get There Together’ project was created by the national steering group after identifying the devastating impact COVID-19 had on people affected by dementia when accessing community occupations. The students collaborated with service users to identify areas that they wanted to visit, creating digital recordings explaining what to expect due to COVID-19 rules. This paper will focus on the conception and development of the Digital Stories Project, which helped increase placement capacity for occupational therapy students, during the COVID-19 pandemic

Index

Seafloor massive sulfide deposits form in remote environments, and the assessment of deposit size and composition through drilling is technically challenging and expensive. To aid the evaluation of the resource potential of seafloor massive sulfide deposits, three-dimensional inverse modelling of geophysical potential field data (magnetic and gravity) collected near the seafloor can be carried out to further enhance geologic models interpolated from sparse drilling. Here, we present inverse modelling results of magnetic and gravity data collected from the active mound at the Trans-Atlantic Geotraverse hydrothermal vent field, located at 26o08'N on the Mid-Atlantic Ridge, using autonomous underwater vehicle (AUV) and submersible surveying. Both minimum-structure and surface geometry inverse modelling methods were utilized. Through deposit-scale magnetic modelling, the outer extent of a chloritized alteration zone within the basalt host rock below the mound was resolved, providing an indication of the angle of the rising hydrothermal fluid and the depth and volume of seawater/hydrothermal mixing zone. The thickness of the massive sulfide mound was determined by modelling the gravity data, enabling the tonnage of the mound to be estimated at 2.17 +/- 0.44 Mt through this geophysics-based, non-invasive approach

PTF10iya: A short-lived, luminous flare from the nuclear region of a star-forming galaxy

We present the discovery and characterisation of PTF10iya, a short-lived (dt ~ 10 d, with an optical decay rate of ~ 0.3 mag per d), luminous (M_g ~ -21 mag) transient source found by the Palomar Transient Factory. The ultraviolet/optical spectral energy distribution is reasonably well fit by a blackbody with T ~ 1-2 x 10^4 K and peak bolometric luminosity L_BB ~ 1-5 x 10^44 erg per s (depending on the details of the extinction correction). A comparable amount of energy is radiated in the X-ray band that appears to result from a distinct physical process. The location of PTF10iya is consistent with the nucleus of a star-forming galaxy (z = 0.22405 +/- 0.00006) to within 350 mas (99.7 per cent confidence radius), or a projected distance of less than 1.2 kpc. At first glance, these properties appear reminiscent of the characteristic "big blue bump" seen in the near-ultraviolet spectra of many active galactic nuclei (AGNs). However, emission-line diagnostics of the host galaxy, along with a historical light curve extending back to 2007, show no evidence for AGN-like activity. We therefore consider whether the tidal disruption of a star by an otherwise quiescent supermassive black hole may account for our observations. Though with limited temporal information, PTF10iya appears broadly consistent with the predictions for the early "super-Eddington" phase of a solar-type star disrupted by a ~ 10^7 M_sun black hole. Regardless of the precise physical origin of the accreting material, the large luminosity and short duration suggest that otherwise quiescent galaxies can transition extremely rapidly to radiate near the Eddington limit; many such outbursts may have been missed by previous surveys lacking sufficient cadence.Comment: 18 pages, 8 figures; revised following referee's comment

Investigating mortality and morbidity associated with UrINary incontinence during Older Womens Secondary Care Admissions and exploring nurses experiences of delivering related care (U-INconti): a mixed methods research protocol

Introduction: Urinary incontinence (UI) is associated with increasing age and is more frequently experienced by women. Despite 40% prevalence in the community, little is known about the prevalence/incidence of UI in older women during hospital admission. UI during hospital admissions, within this group, has also been under-researched in terms of its relationship to specific clinical conditions and mortality rates. Given that UI has serious implications for both patient care and women’s general health and well-being on discharge, this protocol describes a planned research project which aims to determine mortality, morbidity, prevalence and incidence of UI in older women (≥55 years) during hospital admission to inform nursing practice. Additionally, it aims to explore the experience of nurses who deliver women’s care. Methods and analysis: This is an explanatory mixed-methods study consisting of two phases: (1) retrospecitive analysis of electronic patient care records (EPCR) to determine prevalence/incidence of UI, clinical conditions most likely associated with UI and any associations between UI and death, (2) nurse interviews to explore views, knowledge and perceptions of performing the nursing assessment and providing care for older women (≥55 years) with UI during admission. EPCR will be gained from a National Health Service (NHS) teaching hospital. Nurse interviews will be conducted with nurses from an alternative but similar-sized NHS hospital. Ethics and dissemination: Ethical approval is provided by the University of Salford Ethics Committee and regulatory approval by the NHS Health Research Authority (Integrated Research Application System project ID: 303118). Local NHS trust approval to access electronic care records for the purposes of analysis of anonymised data has been provided by one of the two collaborating NHS hospitals. Findings will be disseminated through open-access geriatric or urogynaecology journals and presented to relevant stakeholders at local, national and international meetings including scientific meetings such as the UK Continence Society and International Continence Society