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

Autonomy support, intrinsic motivation, and perceived competence : conceptual and empirical linkages

The purpose of this study was to test three models with regard to the linkages among autonomy support, intrinsic motivation, and perceived competence. The first model is based on Cognitive Evaluation Theory and postulates that teachers’ autonomy support influences changes in intrinsic motivation via changes in perceived academic competence. However, the second and the third model are based on the Diathesis Stress Model of Achievement Processes and posit, respectively, that intrinsic motivation could play a mediating and a moderating role in the relation between teachers’ autonomy support and changes in perceived competence. A total of 215 fifth-grade children participated in a longitudinal study over a 1-year period. Results from regression analyses provided some support for the first model but stronger support for the second and third model

Realtime Optimization of MPC Setpoints using Time-Varying Extremum Seeking Control for Vapor Compression Machines

Recently, model predictive control (MPC) has received increased attention in the HVAC community, largely due to its ability to systematically manage constraints while optimally regulating signals of interest to setpoints. For example, in a common formulation of an MPC control problem for variable compressor speed vapor compression machines, the setpoints often include the zone temperature and the evaporator superheat temperature. However, the energy consumption of vapor compression systems has been shown to be sensitive to these setpoints. Further, while superheat temperature is often preferred because it can be easily correlated to heat exchanger efficiency (and therefore cycle efficiency), direct measurement of superheat is not always available. Therefore, identifying alternate signals in the control of vapor compression machines that correlate to efficiency is desired. Conventionally, methods for maximizing the energy efficiency rely on the use of mathematical models of the physics of vapor compression systems. These model-based approaches attempt to describe the influence of commanded inputs on the thermodynamic behavior of the system and the consumed electrical energy, and they are used to predict the combination of inputs that both meet the heat load requirements and minimize energy consumption. However, these models of vapor compression systems rely on simplifying assumptions in order to produce a mathematically tractable representation. Further, they are difficult to derive and calibrate, and often do not describe variations over long time scales, such as those due to refrigerant losses or accumulation of debris on the heat exchangers. In this paper, we consider a model-free extremum seeking algorithm that adjusts setpoints provided to a model predictive controller. While perturbation-based extremum seeking methods have been known for some time, they suffer from slow convergence rates---a problem emphasized by the long time constants associated with thermal systems. Our method uses a new algorithm (time-varying extremum seeking), which has dramatically faster and more reliable convergence properties. In particular, we regulate the compressor discharge temperature using an MPC controller with setpoints selected from a model-free time-varying extremum seeking algorithm. We show that the relationship between compressor discharge temperature and power consumption is convex (a requirement for this class of realtime optimization), and use time-varying extremum seeking to drive these setpoints to values that minimize power. The results are compared to the traditional perturbation-based extremum seeking approach. Further, because the required cooling capacity (and therefore compressor speed) is a function of measured and unmeasured disturbances, the optimal compressor discharge temperature setpoint must vary according to these conditions. We show that the energy optimal discharge temperature is tracked with the time-varying extremum seeking algorithm in the presence of disturbances

Field theoretic description of the abelian and non-abelian Josephson effect

We formulate the Josephson effect in a field theoretic language which affords a straightforward generalization to the non-abelian case. Our formalism interprets Josephson tunneling as the excitation of pseudo-Goldstone bosons. We demonstrate the formalism through the consideration of a single junction separating two regions with a purely non-abelian order parameter and a sandwich of three regions where the central region is in a distinct phase. Applications to various non-abelian symmetry breaking systems in particle and condensed matter physics are given.Comment: 10 pages no figure

Flow-weighted values of runoff tracers (δ18O, DOC, Ba, alkalinity) from the six largest Arctic rivers

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 35 (2008): L18606, doi:10.1029/2008GL035007.We present new flow-weighted data for δ 18OH2O, dissolved organic carbon (DOC), dissolved barium and total alkalinity from the six largest Arctic rivers: the Ob', Yenisey, Lena, Kolyma, Yukon and Mackenzie. These data, which can be used to trace runoff, are based upon coordinated collections between 2003 and 2006 that were temporally distributed to capture linked seasonal dynamics of river flow and tracer values. Individual samples indicate significant variation in the contributions each river makes to the Arctic Ocean. Use of these new flow-weighted estimates should reduce uncertainties in the analysis of freshwater transport and fate in the upper Arctic Ocean, including the links to North Atlantic thermohaline circulation, as well as regional water mass analysis. Additional improvements should also be possible for assessing the mineralization rate of the globally significant flux of terrigenous DOC contributed to the Arctic Ocean by these major rivers.Supported by the U.S. National Science Foundation (OPP-0229302), the U.S. Geological Survey and the Water Resources Division of Canada’s Department of Indian Affairs and Northern Development

Roles of Noncoding RNAs in Islet Biology.

The discovery that most mammalian genome sequences are transcribed to ribonucleic acids (RNA) has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs), PIWI-associated RNAs, small nucleolar RNAs, tRNA-derived fragments, long non-coding RNAs, and circular RNAs. While the involvement of miRNAs in islet function and in the etiology of diabetes is now well documented, there is emerging evidence indicating that other classes of ncRNAs are also participating in different aspects of islet physiology. The aim of this article will be to provide a comprehensive and updated view of the studies carried out in human samples and rodent models over the past 15 years on the role of ncRNAs in the control of α- and β-cell development and function and to highlight the recent discoveries in the field. We not only describe the role of ncRNAs in the control of insulin and glucagon secretion but also address the contribution of these regulatory molecules in the proliferation and survival of islet cells under physiological and pathological conditions. It is now well established that most cells release part of their ncRNAs inside small extracellular vesicles, allowing the delivery of genetic material to neighboring or distantly located target cells. The role of these secreted RNAs in cell-to-cell communication between β-cells and other metabolic tissues as well as their potential use as diabetes biomarkers will be discussed. © 2020 American Physiological Society. Compr Physiol 10:893-932, 2020

Response of Net Ecosystem Productivity of Three Boreal Forest Stands to Drought

In 2000-03, continuous eddy covariance measurements of carbon dioxide (CO2) flux were made above mature boreal aspen, black spruce, and jack pine forests in Saskatchewan, Canada, prior to and during a 3-year drought. During the 1st drought year, ecosystem respiration (R) was reduced at the aspen site due to the drying of surface soil layers. Gross ecosystem photosynthesis (GEP) increased as a result of a warm spring and a slow decrease of deep soil moisture. These conditions resulted in the highest annual net ecosystem productivity (NEP) in the 9 years of flux measurements at this site. During 2002 and 2003, a reduction of 6% and 34% in NEP, respectively, compared to 2000 was observed as the result of reductions in both R and GEP, indicating a conservative response to the drought. Although the drought affected most of western Canada, there was considerable spatial variability in summer rainfall over the 100-km extent of the study area; summer rainfalls in 2001 and 2002 at the two conifer sites minimized the impact of the drought. In 2003, however, precipitation was similarly low at all three sites. Due to low topographic position and consequent poor drainage at the black spruce site and the coarse soil with low water-holding capacity at the jack pine site almost no reduction in R, GEP, and NEP was observed at these two sites. This study shows that the impact of drought on carbon sequestration by boreal forest ecosystems strongly depends on rainfall distribution, soil characteristics, topography, and the presence of vegetation that is well adapted to these condition

Factors associated with attendee adherence to COVID-19 guidance during the 2021 DCMS Events Research Programme Phase 1

As part of the DCMS Events Research Programme 2021, we surveyed and interviewed attendees of the FA Cup Semi-Final (18th April), Carabao Cup Final (25th April), the FA Cup Final (15th May), the Snooker World Championship (17th April – 3rd May) and Sefton Park music event (2nd May) to examine attendee experiences of the events, perceptions of the COVID-19 guidance, and factors most associated with self-reported adherence