Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart

The Z-disc is a crucial structure of the sarcomere and is implicated in mechanosensation/transduction. Dysregulation of Z-disc proteins often result in cardiomyopathy. We have previously shown that the Z-disc protein Cytoskeletal Heart-enriched Actin-associated Protein (CHAP) is essential for cardiac and skeletal muscle development. Furthermore, the CHAP gene has been associated with atrial fibrillation in humans. Here, we studied the misregulated expression of CHAP isoforms in heart disease. Mice that underwent transverse aortic constriction and calcineurin transgenic (Tg) mice, both models of experimental heart failure, displayed a significant increase in cardiac expression of fetal isoform CHAPb. To investigate whether increased expression of CHAPb postnatally is sufficient to induce cardiomyopathy, we generated CHAPb Tg mice under the control of the cardiac-specific αMHC promoter. CHAPb Tg mice displayed cardiac hypertrophy, interstitial fibrosis and enlargement of the left atrium at three months, which was more pronounced at the age of six months. Hypertrophy and fibrosis were confirmed by evidence of activation of the hypertrophic gene program (Nppa, Nppb, Myh7) and increased collagen expression, respectively. Connexin40 and 43 were downregulated in the left atrium, which was associated with delayed atrioventricular conduction. Tg hearts displayed both systolic and diastolic dysfunction partly caused by impaired sarcomere function evident from a reduced force generating capacity of single cardiomyocytes. This co-incided with activation of the actin signalling pathway leading to the formation of stress fibers. This study demonstrated that the fetal isoform CHAPb initiates progression towards cardiac hypertrophy, which is accompanied by delayed atrioventricular conduction and diastolic dysfunction. Moreover, CHAP may be a novel therapeutic target or candidate gene for screening in cardiomyopathies and atrial fibrillatio

Volunteering in older age : an organizational perspective

Purpose – The purpose of this paper is to shed light on organizational perceptions of the advantages and disadvantages of engaging older volunteers, and on how they might best capitalize on the availability of older volunteers in different countries and sectors. Design/methodology/approach – The paper draws from 74 case studies of voluntary organizations carried out in eight European countries, conducted mainly between spring 2009 and autumn 2010. On-site interviews adopting common guidelines were carried out with organizational representatives. Findings – From the organizational perspectives, some disadvantages of engaging older volunteers are: difficulties matching older volunteers to tasks; problems relating to health and declining capacities; the need for special training efforts. Examples of perceived advantages are: considerable knowledge, skills, experience, reliability and strong commitment of older volunteers. In spite of the very different contexts, objectives and notions of “performance”, cost-benefit assessments of older volunteers do not differ greatly from those generally held by employers about older employees. Countries differ considerably in the recognition of older volunteer potential. Practical implications – Organizational policies and initiatives to capitalize on the availability of older volunteers are examined in the paper. Country and sector-related reflections show how different and changing are the environments for volunteering. Policy makers need to recognise these when implementing active ageing policies. Voluntary organizations should raise their awareness of the need for innovation in volunteer management, especially relating to older people. Originality/value – There has been much research about the experiences of older volunteers and how they benefit from the operations of civil society organizations. The perceptions of the organizations have, however, been neglected and these are explored in this paper

Active ageing in organisations : a case study approach

Purpose – The purpose of this paper is to review good practice examples which promote recruitment and retention of older workers and/or the employability of workers as they age and to examine pathways of practice. Design/methodology/approach – Analysis of qualitative data, drawing on a cross-section selection of 83 good practice case studies in labour organisations in eight European countries: Denmark, France, Germany, Italy, Netherlands, Poland, Sweden and the UK. Findings – The study presented good practice examples and pathways of practice for the four most frequently found dimensions in the sample (training, lifelong learning and knowledge transfer; flexible working; health protection and promotion and job design; career development and mobility management) as well as examples from small to medium-sized enterprises (SMEs) (construction) and the public sector (transport) adopting strategies that fall within these dimensions. These examples show that innovative solutions to the challenge of an ageing workforce have been developed with good outcomes, often combining a number of measures, e.g. mobility management, health promotion and knowledge transfer. However, there is an uneven profile of age management debates and company strategies across Europe (with countries such as Germany and the Netherlands being more advanced). There is also some evidence of a standstill or roll-back of measures during an economic crisis. Originality/value – The paper reviews organisational measures facilitating the extension of working lives, of which many are longstanding and include sectors previously underrepresented in good practice databases (SMEs, public sector)

A 96-well electrochemical method for the screening of enzymatic activities.

International audienceThe rapid electrochemical screening of enzyme activities in bioelectronics is still a challenging issue. In order to solve this problem, we propose to use a 96-well electrochemical assay. This system is composed of 96 screen-printed electrodes on a printed circuit board adapted from a commercial system (carbon is used as the working electrode and silver chloride as the counter/reference electrode). The associated device allows for the measurements on the 96 electrodes to be performed within a few seconds. In this work, we demonstrate the validity of the screening method with the commercial laccase from the fungus Trametes versicolor. The signal-to-noise ratio (S/N) is found to be the best way to analyze the electrochemical signals. The S/N follows a saturation-like mechanism with a dynamic linear range of two decades ranging from 0.5 to 75 ng of laccase (corresponding to enzymatic activities from 62 × 10(-6) to 9.37 × 10(-3) μmol min(-1)) and a sensitivity of 3027 μg(-1) at +100 mV versus Ag/AgCl. Laccase inhibitors (azide and fluoride anions), pH optima, and interfering molecules could also be identified within a few minutes

Rapid electrochemical screening of NAD-dependent dehydrogenases in a 96-well format

International audienceThe electrochemical detection of dehydrogenase activity in crude cell lysates is performed simultaneously using 96 carbon electrodes modified with electrografted phenazines. The method is applied to the screening of a library of formate dehydrogenase mutants obtained by directed evolution

A 96-Well Electrochemical Method for the Screening of Enzymatic Activities

The rapid electrochemical screening of enzyme activities in bioelectronics is still a challenging issue. In order to solve this problem, we propose to use a 96-well electrochemical assay. This system is composed of 96 screen-printed electrodes on a printed circuit board adapted from a commercial system (carbon is used as the working electrode and silver chloride as the counter/reference electrode). The associated device allows for the measurements on the 96 electrodes to be performed within a few seconds. In this work, we demonstrate the validity of the screening method with the commercial laccase from the fungus <i>Trametes versicolor.</i> The signal-to-noise ratio (S/N) is found to be the best way to analyze the electrochemical signals. The S/N follows a saturation-like mechanism with a dynamic linear range of two decades ranging from 0.5 to 75 ng of laccase (corresponding to enzymatic activities from 62 × 10^–6 to 9.37 × 10^–3 μmol min^–1) and a sensitivity of 3027 μg^–1 at +100 mV versus Ag/AgCl. Laccase inhibitors (azide and fluoride anions), pH optima, and interfering molecules could also be identified within a few minutes