The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its microtubule-destabilizing activity

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling is supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics. We show that rotenone treatment of COS-7 cells alters peroxisome morphology and distribution. However, this effect is related to its microtubule-destabilising activity rather than to the generation of oxidative stress. Rotenone also induced alterations in mitochondrial morphology, which – in contrast to its effect on peroxisomes - were dependent on the generation of ROS but independent of its microtubule-active properties. The importance of our findings for the peroxisome-mitochondria redox relationship and the interpretation of in cellulo and in vivo studies with rotenone, which is widely used to study Parkinson’s disease, are discussed.We would like to acknowledge the support of T. A. Schrader, N. A. Bonekamp and J. Jordan (University of Castilla-La Mancha, Albacete, Spain). This work was supported by the Biotechnology and Biological Sciences Research Council (BB/K006231/1, BB/N01541X/1 to M.S.), the Portuguese Foundation for Science and Technology and FEDER/COMPETE (SFRH/BPD/37725/2007 to M.G.L), the University of Aveiro, PT and CLES, University of Exeter, UK. M.S. is supported by a Marie Curie Initial Training Network (ITN) action PerFuMe (316723)

The genealogy of judgement: towards a deep history of academic freedom

The classical conception of academic freedom associated with Wilhelm von Humboldt and the rise of the modern university has a quite specific cultural foundation that centres on the controversial mental faculty of 'judgement'. This article traces the roots of 'judgement' back to the Protestant Reformation, through its heyday as the signature feature of German idealism, and to its gradual loss of salience as both a philosophical and a psychological concept. This trajectory has been accompanied by a general shrinking in the scope of academic freedom from the promulgation of world-views to the offering of expert opinion

Integrating coaching and positive psychology: Concepts and practice

The abstract in included in the text

Intent and outcomes from the Retrofit for the Future programme: key lessons

The Retrofit for the Future programme, sponsored by UK government's Technology Strategy Board (TSB) from 2009 to 2013, demonstrated innovative approaches to deep retrofitting of social housing, using a whole-house approach for achieving an 80% CO2 reduction target. The intent and outcomes of this programme (in which all authors participated) are critically examined through a cross-project meta-study of the primary data, substantiated by insights from secondary sources. Given that only three (out of 45) projects met the expected CO2 target in reality, despite generous funding and professional expertise, it suggests that decarbonizing existing housing will not be particularly easy. Important lessons are found in this initiative's formulation, target setting, monitoring and evaluation procedures, and feedback mechanisms. These lessons can inform the formulation, delivery and effectiveness of future national energy retrofit programmes. Furthermore, to support the ‘scaling up’ of effective retrofit programmes and reduce the gap between intent and outcome, it is recommended that attention be moved from what level of CO2 reductions are to be achieved to how (delivery models) these radical reductions can be achieved and by whom (supply chain). Such alternative delivery models to the ‘whole house’ approach include retrofit over time, city-scale retrofit and community-based energy retrofits

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994

The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980–1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980–1984, 1985–1989 and 1990–1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983–1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980–1986 and 54% in 1987–1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980–1986, 42 vs 30%; 1987–1992, 59 vs 42%; 1993–1994, 54 vs 43%. During 1985–1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985–1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate

Become the best coach you can be: the role of coach training and coaching experience in workplace coaching quality and quality control

This paper explores whether coach training or coaching experience leads to better coaching quality and quality control. In two large studies, both coaches (N1 = 2267) and personnel managers who book coaches for their company (N2 = 754) answered questions about coaching quality and quality control. The results show that more coach training leads to not only a better self-perceived coaching quality (Study 1) but also a better other-perceived coaching-quality (Study 2); moreover, more coach training positively affects quality control. It is remarkable that coaching experience showed no significant relation regarding other-perceived coaching quality and quality control. Study 2 further revealed that references lead to more recommendations but not to a better coaching quality or quality control. Thus, coach training is an essential factor when selecting organizational coaches. Further research is needed to understand the impact of different approaches to coach trainings on coaching outcomes

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Parental bonding and identity style as correlates of self-esteem among adult adoptees and nonadoptees

Adult adoptees (n equals 100) and non-adoptees (n equals 100) were compared with regard to selfesteem, identity processing style, and parental bonding. While some differences were found with regard to self-esteem, maternal care, and maternal overprotection, these differences were qualified by reunion status such that only reunited adoptees differed significantly from nonadoptees. Moreover, hierarchical regression analyses indicated that parental bonding and identity processing style were more important than adoptive status per se in predicting self esteem. Implications for practitioners who work with adoptees are discussed

Near-infrared wavelength intersubband transitions in GaN∕AlN short period superlattices

Intersubband transitions in GaN∕AlN short period superlattices prepared by molecular beam epitaxy were investigated using the optical absorption technique. The peak position wavelengths of these transitions are found to span the spectral range of 1.35–2.90μm for samples cut into 45° waveguides with GaNquantum well thicknesses ranging between 1.70 and2.41nm. The Fermi energy levels are estimated from the carrier concentrations, which were measured using an electrochemical capacitance-voltage profiler. The well widths were inferred from comparing the measured peak position energy of the intersubband transitions and the bound state energy levels calculated using the transfer matrix method