Alien Registration- Rutter, Rhea C. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/21875/thumbnail.jp

Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.AIMS/HYPOTHESIS: Ageing can lead to reduced insulin sensitivity and loss of pancreatic beta cell function, predisposing individuals to the development of diabetes. The aim of this study was to assess the contribution of microRNAs (miRNAs) to age-associated beta cell dysfunction. METHODS: The global mRNA and miRNA profiles of 3- and 12-month-old rat islets were collected by microarray. The functional impact of age-associated differences in miRNA expression was investigated by mimicking the observed changes in primary beta cells from young animals. RESULTS: Beta cells from 12-month-old rats retained normal insulin content and secretion, but failed to proliferate in response to mitotic stimuli. The islets of these animals displayed modifications at the level of several miRNAs, including upregulation of miR-34a, miR-124a and miR-383, and downregulation of miR-130b and miR-181a. Computational analysis of the transcriptomic modifications observed in the islets of 12-month-old rats revealed that the differentially expressed genes were enriched for miR-34a and miR-181a targets. Indeed, the induction of miR-34a and reduction of miR-181a in the islets of young animals mimicked the impaired beta cell proliferation observed in old animals. mRNA coding for alpha-type platelet-derived growth factor receptor, which is critical for compensatory beta cell mass expansion, is directly inhibited by miR34a and is likely to be at least partly responsible for the effects of this miRNA. CONCLUSIONS/INTERPRETATION: Changes in the level of specific miRNAs that occur during ageing affect the proliferative capacity of beta cells. This might reduce their ability to expand under conditions of increased insulin demand, favouring the development of type 2 diabetes.Swiss National Science FoundationFondation Francophone pour la Recherche sur le DiabèteWellcome Trust Senior Investigator AwardMRC Programme GrantRoyal Society Wolfson Research Merit AwardWellcome Trust project gran

Influence of Nitrogen Availability on Aminotransferases in Lemna minor L

Protein contents and glutamate: glyoxylate, serine: glyoxylate, alanine: glyoxylate and glutamate: pyruvate aminotransferase activities per gram fresh weight declined sharply when Lemna minor L., previously grown on nitrate medium, was starved of nitrogen. Nitrogen replenishment after 5 d caused complete recovery of these parameters with higher values in ammonium-fed than nitrate-fed plants 7 d after transfer of plants from nitrogen-free medium. Glutamate: glyoxylate and alanine: glyoxylate aminotransferase specific activities (based on total extracted protein) showed little change with nitrogen availability. Serine: glyoxylate aminotransferase increased slowly during nitrogen starvation and decreased following nitrogen replenishment whether with ammonium or nitrate. After 1 d of nitrogen starvation the specific activity of glutamate: pyruvate aminotransferase declined; it increased following nitrogen replenishment and ammonium gave rise to agreater activity than nitrate. The results are discussed in relation to the differences in stability of the various enzymes relative to the overall protein turnover rat

Applications of alpha space

We extend the definition of ‘alpha space’ as introduced in [1] to two spacetime dimensions. We discuss how this can be used to find conformal block decompositions of known functions and how to easily recover several lightcone bootstrap results. In the second part of the paper we establish a connection between alpha space and the Lorentzian inversion formula of [2]

Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.

SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans

On Resilient Behaviors in Computational Systems and Environments

The present article introduces a reference framework for discussing resilience of computational systems. Rather than a property that may or may not be exhibited by a system, resilience is interpreted here as the emerging result of a dynamic process. Said process represents the dynamic interplay between the behaviors exercised by a system and those of the environment it is set to operate in. As a result of this interpretation, coherent definitions of several aspects of resilience can be derived and proposed, including elasticity, change tolerance, and antifragility. Definitions are also provided for measures of the risk of unresilience as well as for the optimal match of a given resilient design with respect to the current environmental conditions. Finally, a resilience strategy based on our model is exemplified through a simple scenario.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/s40860-015-0002-6 The paper considerably extends the results of two conference papers that are available at http://ow.ly/KWfkj and http://ow.ly/KWfgO. Text and formalism in those papers has been used or adapted in the herewith submitted pape

National child measurement programme: detailed analysis of the 2007/08 national dataset

This report presents detailed secondary analyses to further our understanding of the epidemiology of child height, weight and Body Mass Index (BMI) across England. It attempts to explain some of the findings presented in the NHS Information Centre for Health and Social Care 2007/08 NCMP report. The report provides analysis of PCT participation levels and investigates data quality issues in the collection of the 2007/08 NCMP dataset. Data on prevalence of underweight, healthy weight, overweight and obesity are analysed, comparing the 2007/08 data to the 2006/07, and the 1990 baseline. Analyses by deprivation and ethnic group are also included. The report further examines how the distribution of BMI differs by age and sex of the child sample population, and investigates changes since the 1990 baseline. It looks at the association between obesity prevalence and characteristics of the individual children and the PCTs in which they were measured using regression analysis

Learning safely from error: Reconsidering the ethics of simulation-based medical education through ethnography

‘Human factors’ is an influential rationale in the UK national health service to understand mistakes, risk and safety. Although there have been studies examining its implications in workplaces, there has been little investigation of how it is taught, as a form of professional morality. This article draws on an observational study of human factors teaching in four hospital simulation centres in London, UK. Its main argument is that the teaching of human factors is realised through an identification and positive evaluation of ‘non-technical skills’ and the espousal of ‘non-judgemental’ pedagogy, both of which mean that mistakes cannot be made. Professional solidarity is then maintained on the absence of mistakes. We raise questions about the ethics of this teaching. The study is situated within a history of ethnographic accounts of medical mistakes, to explore the relationship between claims to professional knowledge and claims about failure