Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres

A number of studies have previously proposed the existence of glucocorticoid receptors on the plasma membrane of many cell types including skeletal muscle fibres. However, their exact localisation and the cellular signalling pathway(s) they utilise to communicate with the rest of the cell are still poorly understood. In this study, we investigated the localisation and the mechanism(s) underlying the non-genomic physiological functions of these receptors in mouse skeletal muscle cells. The results show that the receptors were localised in the cytoplasm in myoblasts, in the nucleus in myotubes and in the extracellular matrix, in satellite cells and in the proximity of mitochondria in adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent manner. Treating small skeletal muscle fibre bundles with the synthetic glucocorticoid, beclomethasone dipropionate, increased the phosphorylation (=activation) of extracellular-signal regulated kinase 1&2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. This occurred within 5min and depended on the fibre-type and the duration of the treatment. It was also abolished by the glucocorticoid receptor inhibitor, mifepristone, and a monoclonal antibody against the receptor. From these results we conclude that the non-genomic/non-canonical physiological functions of glucocorticoids, in adult skeletal muscle fibres are mediated by a glucocorticoid receptor localised in the extracellular matrix, in satellite cells and close to mitochondria and involve activation of the MAPK pathway

Metacarpophalangeal pattern profile analysis of a sample drawn from a North Wales population

This is tha author's PDF version of an article published in Annals of human biology© 2001. The definitive version is available at http://www.tandf.co.uk/journalsSexual dimorphism and population differences were investigated using metacarpophalangeal pattern profile (MCPP) analysis. Although it is an anthropmetric technique, MCPP analysis is more frequently used in genetic syndrome analysis and has been under-used in the study of human groups. The present analysis used a series of hand radiographics from Gwynedd, North Wales, to make comparisons, first, between the sexes within the sample and then with previously reported data from Japan. The Welsh sexes showed MCPP analyses that indicated size and shape differences but certain similarities in shape were also evident. Differences with the Japanese data were more marked. MCPP anlysis is a potentially useful anthropmetric technique but requires further statistical development

Comment on 'A first map of tropical Africa's above-ground biomass derived from satellite imagery'

Copyright Institute of Physics © 2011We present a critical evaluation of the above-ground biomass (AGB) map of Africa published in this journal by Baccini et al (2008 Environ. Res. Lett. 3 045011). We first test their map against an independent dataset of 1154 scientific inventory plots from 16 African countries, and find only weak correspondence between our field plots and the AGB value given for the surrounding 1 km pixel by Baccini et al. Separating our field data using a continental landcover classification suggests that the Baccini et al map underestimates the AGB of forests and woodlands, while overestimating the AGB of savannas and grasslands. Secondly, we compare their map to 216 000 × 0.25 ha spaceborne LiDAR footprints. A comparison between Lorey's height (basal-area-weighted average height) derived from the LiDAR data for 1 km pixels containing at least five LiDAR footprints again does not support the hypothesis that the Baccini et al map is accurate, and suggests that it significantly underestimates the AGB of higher AGB areas. We conclude that this is due to the unsuitability of some of the field data used by Baccini et al to create their map, and overfitting in their model, resulting in low accuracies outside the small areas from which their field data are drawn

Advanced multivariate data analysis to determine the root cause of trisulfide bond formation in a novel antibody-peptide fusion

Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can be influenced by multiple interacting process parameters. Identifying their root cause is a major challenge in biopharmaceutical production. To address this issue, this paper describes the novel application of advanced multivariate data analysis (MVDA) techniques to identify the process parameters influencing TSB formation in a novel recombinant antibody-peptide fusion expressed in mammalian cell culture. The screening dataset was generated with a high-throughput (HT) micro-bioreactor system (Ambr(TM) 15) using a design of experiments (DoE) approach. The complex dataset was firstly analyzed through the development of a multiple linear regression model focusing solely on the DoE inputs and identified the temperature, pH and initial nutrient feed day as important process parameters influencing this quality attribute. To further scrutinize the dataset, a partial least squares model was subsequently built incorporating both on-line and off-line process parameters and enabled accurate predictions of the TSB concentration at harvest. Process parameters identified by the models to promote and suppress TSB formation were implemented on five 7 L bioreactors and the resultant TSB concentrations were comparable to the model predictions. This study demonstrates the ability of MVDA to enable predictions of the key performance drivers influencing TSB formation that are valid also upon scale-up

A computational model based on human performance for fluid management in critical care

Computational simulation is one of the most important ways of reproducing the dynamic responses of a Cyber Physical System using a model of the system. The simulation discovers areas of differential system performance and allows linking such performance back to system characteristics. In the medical domain, patient simulators are used to train physicians in patient management. One critical question is how to verify these systems under realistic human (physician) input. This requires the creation of realistic human models that would be able to capture human cognitive and decision abilities and limitations. Verification of such an overall physician-patient model would result in two advantages: (a) since physicians realistically would not give all possible inputs to the system, verification could be more efficient and (b) the verification may uncover areas of poor human performance. In this paper, we describe our methodology and results in creating a computational model of human fluid management in critical care, based on human experiments

Formulation and performance of variational integrators for rotating bodies

Variational integrators are obtained for two mechanical systems whose configuration spaces are, respectively, the rotation group and the unit sphere. In the first case, an integration algorithm is presented for Euler’s equations of the free rigid body, following the ideas of Marsden et al. (Nonlinearity 12:1647–1662, 1999). In the second example, a variational time integrator is formulated for the rigid dumbbell. Both methods are formulated directly on their nonlinear configuration spaces, without using Lagrange multipliers. They are one-step, second order methods which show exact conservation of a discrete angular momentum which is identified in each case. Numerical examples illustrate their properties and compare them with existing integrators of the literature

Identification of capacity development indicators for faculty development programs: A nominal group technique study.

BackgroundAlthough there have been many research studies of the effectiveness of faculty development in health profession education, the contribution of these programs to organizational development through capacity development has not been studied. Further understanding of capacity development requires appropriate indicators and no previous indicators for faculty development of health profession educators were identified. The aim of the study was to identify indicators of capacity development in the context of faculty development programs at Tehran University of medical sciences (TUMS).MethodsA nominal group technique session was conducted with key informants from faculty development program providers to generate and prioritize a list of capacity development indicators.ResultsA list of 26 indicators was generated and five categories were identified: Development and innovation in teaching and learning process, Development and innovation in communication and collaboration at different levels, Development and sustaining faculty development programs, Development of educational leadership and management, Development in scholarship.ConclusionsCapacity development for faculty development interventions of health profession educators is a process of engagement within a wider system, including individual and collective action, and involves the socialization of the teachers into suitable roles through professional identity development and participation within the wider system

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Smart homes and their users:a systematic analysis and key challenges

Published research on smart homes and their users is growing exponentially, yet a clear understanding of who these users are and how they might use smart home technologies is missing from a field being overwhelmingly pushed by technology developers. Through a systematic analysis of peer-reviewed literature on smart homes and their users, this paper takes stock of the dominant research themes and the linkages and disconnects between them. Key findings within each of nine themes are analysed, grouped into three: (1) views of the smart home-functional, instrumental, socio-technical; (2) users and the use of the smart home-prospective users, interactions and decisions, using technologies in the home; and (3) challenges for realising the smart home-hardware and software, design, domestication. These themes are integrated into an organising framework for future research that identifies the presence or absence of cross-cutting relationships between different understandings of smart homes and their users. The usefulness of the organising framework is illustrated in relation to two major concerns-privacy and control-that have been narrowly interpreted to date, precluding deeper insights and potential solutions. Future research on smart homes and their users can benefit by exploring and developing cross-cutting relationships between the research themes identified