Skeletal muscle differentiation drives a dramatic downregulation of RNA polymerase III activity and differential expression of Polr3g isoforms

Gene regulatory networks underpinning skeletal muscle determination and differentiation have been extensively investigated, providing molecular insights into how cell lineages are established during development. These studies have exclusively focused on the transcriptome downstream of RNA polymerase II (Pol II). RNA polymerase III (Pol III) drives the production of tRNAs and other small RNAs essential for the flow of genetic information from gene to protein and we have found that a specific isoform of a subunit unique to Pol III is expressed early in the myogenic lineage. This points to the possibility that additional regulatory networks exist to control the production of Pol III transcripts during skeletal muscle differentiation. We describe the differential expression of Polr3g and its alternate isoform Polr3gL during embryonic development and using a custom tRNA microarray, we demonstrate their distinct activity on the synthesis of tRNA isoacceptors. We show that Pol III dependent transcripts are dramatically down-regulated during the differentiation of skeletal muscle, as are mRNAs coding for Pol III associated proteins Brf1 and Brf2, while Polr3gL is up-regulated alongside contractile protein genes. Forcing Polr3g expression in this context results in a partial reversal of myogenic differentiatio

Skeletal muscle differentiation drives a dramatic downregulation of RNA polymerase III activity and differential expression of Polr3g isoforms

Gene regulatory networks underpinning skeletal muscle determination and differentiation have been extensively investigated, providing molecular insights into how cell lineages are established during development. These studies have exclusively focused on the transcriptome downstream of RNA polymerase II (Pol II). RNA polymerase III (Pol III) drives the production of tRNAs and other small RNAs essential for the flow of genetic information from gene to protein and we have found that a specific isoform of a subunit unique to Pol III is expressed early in the myogenic lineage. This points to the possibility that additional regulatory networks exist to control the production of Pol III transcripts during skeletal muscle differentiation. We describe the differential expression of Polr3g and its alternate isoform Polr3gL during embryonic development and using a custom tRNA microarray, we demonstrate their distinct activity on the synthesis of tRNA isoacceptors. We show that Pol III dependent transcripts are dramatically down-regulated during the differentiation of skeletal muscle, as are mRNAs coding for Pol III associated proteins Brf1 and Brf2, while Polr3gL is up-regulated alongside contractile protein genes. Forcing Polr3g expression in this context results in a partial reversal of myogenic differentiation

Using Participatory Action Research in the Development of an Innovative Cottage Hospice Model of Care in the United Kingdom

Title Using Participatory Action Research in the development of an innovative Cottage Hospice model of care in the United Kingdom Objectives a) To contribute to the development of the Cottage Hospice programme and its constituent components. b) To ascertain barriers to and facilitators of Cottage Hospice using action cycles to address identified challenges. Methods Our three-phase Participatory Action Research (PAR) study comprised: 1) A situational analysis using documents (n=150) and stakeholder qualitative interviews (n=28). 2) A Core Action Group oversaw action cycles designed to address challenges identified from the situational data. Local stakeholders participated in a deliberative workshop where study results were presented and refined. 3) An end of study conference is planned in order to disseminate learning to a wider stakeholder audience Results Results presented here align with the objectives in terms of identifying challenges and contributing to the development of the Cottage Hospice programme. Our situational analysis revealed growing support and enthusiasm for the model among hospice staff and volunteers, over time. However, anxieties regarding the viability, reach and conceptual clarity of Cottage Hospice were identified, as were concerns about communication systems and staff feedback to the planning team. Early results demonstrated a need to gather the views of a wider range of health and social care providers regarding the local impact of the initiative. Action cycles included a focus on determining who might use Cottage Hospice; what support family caregivers may need; and conceptual explorations of ‘family’. The deliberative workshop enabled findings to be refined in discussion with those most invested in Cottage Hospice, feeding into the final report and dissemination plans. Conclusions Using PAR democratises the research process and provided an opportunity for all interested parties to contribute to the development of Cottage Hospice. It enabled ‘ground up’ development and ownership of the model and led to contextualised solutions to identified challenges. Despite the locally situated setting, we believe the lessons learned are widely applicable

Researching an innovative Cottage Hospice model of care:An academic and hospice partnership

Background: Exploring innovative models of hospice, palliative and end of life care is imperative to meet contemporary demands in caring for those approaching the end of life. To this end, a new Cottage Hospice model is being developed in the south of England. The hospice concerned commissioned a concurrent two-year research study to track the programme development. This addresses the call for hospices to work with academics in determining which types of care work best.1 Aim: To evaluate the development of Cottage Hospice using a research approach where solutions to challenges are developed collaboratively with a range of stakeholders. Results from this work will assist decision making as the programme proceeds. Methods: Participatory Action Research is being used to evaluate the programme. A situational analysis using documents (n=26) and interviews (n=30) explored the programmes foundations. Action cycles (n=6-10) in which issues are worked on in small groups to agreed solutions follows the initial phase. Findings will be fed back to stakeholders in workshops to share and refine results. Results: Initial results demonstrate a need for conceptual clarity about the model to be sought between staff, volunteers, service users and external stakeholders in order to achieve a shared vision and support for the programme. Action cycles to address conceptual understandings and practical issues including staffing and community engagement are planned. It is anticipated that these may highlight areas for further action cycles. Conclusions: The early involvement of an academic research team in evaluating a new model of hospice care represents an embedded and enlightened approach in which research is not an afterthought. We believe this strengthens the basis for this new initiative. Gaining an in-depth, evidence based understanding of how challenges were resolved in the implementation of Cottage Hospice will be of use to others in the sector planning similar initiatives. 1. Payne S, Preston N, Turner M, Rolls L (2013). Research in palliative care: Can hospices afford not to be involved? London, Hospice UK

Alumnae Association Bulletin of the School of Nursing, 1972

Alumnae Calendar The President\u27s Message Officers and Chairmen of Committees Financial Report Address by President Herbut School of Nursing Report School of Practical Nursing Report Report by Dr. Mary Louise Soentgen, M.D., F.A.A.P. Report of Patient Services Department Report of Staff Nurses\u27 Association Progress Report of Hospital Activities Scholarship Committee Report - Clerk-Typist Annual Luncheon - Head Table Social Events for 1971-1972 Missing Alumnae Members Jefferson Today Ways and Means Committee Report Constitution and By-Laws Report Sick and Welfare Committee Women\u27s Board Report Baccalaureate Degree Program Luncheon Pictures Resume of Minutes of Alumnae Association Meeting Class News Poem by Rosa Diseroad - 1923 Marriages Births - Hello World In Memoriam Notice

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers’ narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers

A study to determine the effect of summer vacation on reading achievement in grades three, four and five,

Thesis (M.A.)--Boston Universit

Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells

Background/Objectives Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk. Subjects/Methods In this observational cohort study, we recruited 13 lean (pre-pregnancy BMI <25.0 kg/m2) and 24 overweight-obese (‘ov-ob’, BMI ≥25.0 kg/m2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines. Results: 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR <0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR <0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in levels of total free fatty acids (lean: 95.5 ± 37.1 ug/ml, ov-ob: 124.1 ± 46.0 ug/ml, P=0.049), palmitate (lean: 34.5 ± 12.7 ug/ml, ov-ob: 46.3 ± 18.4 ug/ml, P=0.03) and stearate (lean: 20.8 ± 8.2 ug/ml, ov-ob: 29.7 ± 17.2 ug/ml, P=0.04), in infants of overweight-obese mothers. Conclusion: Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally-programmed differences in oxidative and lipid metabolism

De Plenderleith a Al Gore: o ideário vigente na conservação de bens culturais móveis no século XXI

O texto discute idéias predominantes, hoje, nas práticas de conservação de bens culturais móveis no Ocidente. São apontadas, também, algumas tendências de pensamento em diferentes contextos de trabalho, identificando-se eventuais mudanças e semelhanças entre as idéias anteriormente vigentes e aquelas que muito provavelmente sejam, já, um legado para este novo século.This article discusses the prevailing concepts referring to the conservation of cultural heritage collections. Some trends such as some lines of thought are also indicated, identifying occasional changes and similarities among the ideas previously in force and those that, probably, are already a legacy for this new century

Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019–2021

Objective: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. Design: We conducted a community-based cross-sectional seroprevalence study in participants aged 0–18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. Results: Post-first wave (June–August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10–14 years old) to 9.5% (participants 5–9 years old). By April–June 2021, this had increased to 19.9%, varying from 13.9% (participants 0–4 years old) to 32.7% (participants 15–18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. Conclusions: Approximately one-third of participants aged 15–18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. Trial registration number: NCT04061382