Conformational Change of Mitochondrial Complex I Increases ROS Sensitivity During Ischemia

Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities of reactive oxygen species (ROS) and resultant damage to mitochondrial enzymes is considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) and deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium in several tissues under ischemic conditions in vivo and investigated the sensitivity of both forms of the heart enzyme to ROS.

Results: We found that in the heart, t½ of complex I deactivation during ischemia was 10?min, and that reperfusion resulted in the return of A/D equilibrium to its initial level. The rate of superoxide generation by complex I was higher in ischemic samples where content of the D-form was higher. Only the D-form was susceptible to inhibition by H2O2 or superoxide, whereas turnover-dependent activation of the enzyme resulted in formation of the A-form, which was much less sensitive to ROS. The mitochondrial-encoded subunit ND3, most likely responsible for the sensitivity of the D-form to ROS, was identified by redox difference gel electrophoresis.

Innovation: A combined in vivo and biochemical approach suggests that sensitivity of the mitochondrial system to ROS during myocardial I/R can be significantly affected by the conformational state of complex I, which may therefore represent a new therapeutic target in this setting.

Conclusion: The presented data suggest that transition of complex I into the D-form in the absence of oxygen may represent a key event in promoting cardiac injury during I/R.

Towards mapping the late Quaternary vegetation change of Europe

The number of well-dated pollen diagrams in Europe has increased considerably over the last 30 years and many of them have been submitted to the European Pollen Database (EPD). This allows for the construction of increasingly precise maps of Holocene vegetation change across the continent. Chronological information in the EPD has been expressed in uncalibrated radiocarbon years, and most chronologies to date are based on this time scale. Here we present new chronologies for most of the datasets stored in the EPD based on calibrated radiocarbon years. Age information associated with pollen diagrams is often derived from the pollen stratigraphy itself or from other sedimentological information. We reviewed these chronological tie points and assigned uncertainties to them. The steps taken to generate the new chronologies are described and the rationale for a new classification system for age uncertainties is introduced. The resulting chronologies are fit for most continental-scale questions. They may not provide the best age model for particular sites, but may be viewed as general purpose chronologies. Taxonomic particularities of the data stored in the EPD are explained. An example is given of how the database can be queried to select samples with appropriate age control as well as the suitable taxonomic level to answer a specific research question. © 2013 The Author(s).

Change of visual acuity recording methods in clinical studies across the years

Purpose: To report any differences in the visual acuity (VA) recording method used in peer-reviewed ophthalmology clinical studies over the past decade. Methods: We reviewed the method of assessing and reporting VA in 160 clinical studies from 2 UK and 2 US peer-reviewed journals, published in 1994 and 2004. Results: The method used to assess VA was specified in 62.5% of UK-published and 60% of US-published papers. In the results sections of the UK publications the VA measurements presented were Snellen acuity (n = 58), logMAR acuity (n = 20) and symbol acuity (n = 1). Similarly in the US publications the VA was recorded in the results section using Snellen acuity (n = 60) and logMAR acuity (n = 14). Overall 10% of the authors appeared to convert Snellen acuity measurements to logMAR format. Five studies (3%) chose to express Snellen-type acuities in decimal form, a method which can easily lead to confusion given the increased use of logMAR scoring systems. Conclusion: The authors recommend that to ensure comparable visual results between studies and different study populations it would be useful if clinical scientists worked to standardized VA testing protocols and reported results in a manner consistent with the way in which they are measured. Copyright © 2008 S. Karger AG.

Next-generation sequencing: a change of paradigm in molecular diagnostic validation

Next-generation sequencing (NGS) is beginning to show its full potential for diagnostic and therapeutic applications. In particular, it is enunciating its capacity to contribute to a molecular taxonomy of cancer, to be used as a standard approach for diagnostic mutation detection, and to open new treatment options that are not exclusively organ-specific. If this is the case, how much validation is necessary and what should be the validation strategy, when bringing NGS into the diagnostic/clinical practice? This validation strategy should address key issues such as: what is the overall extent of the validation? Should essential indicators of test performance such as sensitivity of specificity be calculated for every target or sample type? Should bioinformatic interpretation approaches be validated with the same rigour? What is a competitive clinical turnaround time for a NGS-based test, and when does it become a cost-effective testing proposition? While we address these and other related topics in this commentary, we also suggest that a single set of international guidelines for the validation and use of NGS technology in routine diagnostics may allow us all to make a much more effective use of resources.

High resolution monitoring of surface morphological change of building limestones in response to simulated salt weathering

A salt weathering simulation using a mix of sodium chloride (5%) and magnesium sulphate (5%) in a salt corrosion cabinet and five granular limestones is described. Progressive surface loss from vertical exposed faces was mapped using a high resolution (sub-millimetre) object scanner (Konica Minolta Vi9i). Patterns of loss are related to surface porosity/permeability measurements obtained using a hand-held gas permeameter. Introduction of this spatial dimension into damage assessment is seen as essential for understanding the initial conditions that allow surface loss to be triggered, and changes in surface characteristics as weathering proceeds which dictate subsequent decay in space and time. Preliminary observations suggest that scanning at this high resolution is particularly valuable in quantifying very subtle trends and distortions that are pre-cursors to material loss, including surface swelling and pore filling.

Awareness of sunburn in childhood, use of sunbeds and change of moles in Denmark, Northern Ireland, Norway and Sweden

Background: Malignant melanoma (MM) is increasing rapidly in Northern Europe. To reduce incidence and mortality through earlier diagnosis, public awareness of MM is important. Thus, we aim to examine awareness of risk factors and a symptom of MM, and how awareness varies by country and socio-demographic factors in Denmark, Northern Ireland (NI), Norway and Sweden.

Methods: Population-based telephone interviews using the ‘Awareness and Beliefs about Cancer’ measure were conducted in 2011 among 8355 adults ≥50 years as part of the International Cancer Benchmarking Partnership Module 2. Prevalence ratios (PRs) with 95% confidence intervals were calculated.

Results: In these four countries, lowest awareness was found for ‘sunburn in childhood’ (63%), whereas awareness was high for ‘use of sunbeds’ (91%) and ‘mole change’ (97%). Lack of awareness of ‘sunburn in childhood’ was more prevalent among respondents from Norway [PR = 1.38 (1.28–1.48)] but less prevalent among respondents from Northern Ireland (NI) [PR = 0.78 (0.72–0.85)] and Sweden [PR = 0.86 (0.79–0.93)] compared with respondents from Denmark. Lack of awareness of ‘use of sunbeds’ was more prevalent among respondents from Norway [PR = 2.99 (2.39–3.74)], Sweden [PR = 1.57 (1.22–2.00)], and NI [PR = 1.65 (1.30–2.10)] compared with respondents form Denmark. Being a man, age ≥70, living alone, and having lower education, were each independently associated with lack of MM-awareness.

Conclusions: The results indicate relatively low awareness of ‘sunburn in childhood’ as a risk factor for MM, and important disparities in MM-awareness across countries and socio-demographic groups. Improved and more directed initiatives to enhance public MM-awareness, particularly about ‘sunburn in childhood’, are needed.

Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex i

Mitochondrial complex I is a large, membrane-bound enzyme central to energy metabolism, and its dysfunction is implicated in cardiovascular and neurodegenerative diseases. An interesting feature of mammalian complex I is the so-called A/D transition, when the idle enzyme spontaneously converts from the active (A) to the de-active, dormant (D) form. The A/D transition plays an important role in tissue response to ischemia and rate of the conversion can be a crucial factor determining outcome of ischemia/reperfusion. Here, we describe the effects of alkali cations on the rate of the D-to-A transition to define whether A/D conversion may be regulated by sodium.At neutral pH (7–7.5) sodium resulted in a clear increase of rates of activation (D-to-A conversion) while other cations had minor effects. The stimulating effect of sodium in this pH range was not caused by an increase in ionic strength. EIPA, an inhibitor of Na+/H+antiporters, decreased the rate of D-to-A conversion and sodium partially eliminated this effect of EIPA. At higher pH (> 8.0), acceleration of the D-to-A conversion by sodium was abolished, and all tested cations decreased the rate of activation, probably due to the effect of ionic strength.The implications of this finding for the mechanism of complex I energy transduction and possible physiological importance of sodium stimulation of the D-to-A conversion at pathophysiological conditions in vivo are discussed.

Patterns of Behaviour, Group Structure and Reproductive Status Predict Levels of Glucocorticoid Metabolites in Zoo-Housed Ring-Tailed Lemurs, Lemur catta

In ring-tailed lemurs, Lemur catta, the factors modulating hypothalamic-pituitaryadrenal (HPA) activity differ between wild and semi-free-ranging populations. Here we assess factors modulating HPA activity in ring-tailed lemurs housed in a third environment: the zoo. First we validate an enzyme immunoassay to quantify levels of glucocorticoid (GC) metabolites in the faeces of L. catta . We determine the nature of the femalefemale dominance hierarchies within each group by computing David's scores and examining these in relation to faecal GC (fGC). Relationships between female age and fGC are assessed to evaluate potential age-related confounds. The associations between fGC, numbers of males in a group and reproductive status are explored. Finally, we investigate the value of 7 behaviours in predicting levels of fGC. The study revealed stable linear dominance hierarchies in females within each group. The number of males in a social group together with reproductive status, but not age, influenced fGC. The 7 behavioural variables accounted for 68% of the variance in fGC. The amounts of time an animal spent locomoting and in the inside enclosure were both negative predictors of fGC. The study highlights the flexibility and adaptability of the HPA system in ring-tailed lemurs.

Islands of pain in a sea of change: Behaviour analysis and bereavement,

The paper Bereavement: A behavioural process (Dillenburger & Keenan, 1994) was first published within a vacuum of behaviour analytic thinking or research in this field. The paper was meant to be a first step in stimulating others to contribute to the understanding of one of the most complex, yet most universal, human behavioural processes. The only behaviour analyst addressing the issues directly was Calkin (1990). Recently, after reading our original 1994 paper, Beth Sulzer-Azaroff suggested that we should solicit comments directly from the behaviour analytic community. This we did with the help of Erik Arntzen and now the reprint and the commentaries in this edition of the European Journal of Behaviour Analysis (EJBA) fully embrace and extend the contribution of behaviour analysis to the understanding of the behavioural process that is bereavement.

The role played by a range of psychological variables in nurses’ handwashing behaviour

Background: Psychological models of behaviour change are used to predict patients’ health behaviours but have rarely been used to explore healthcare professionals’ health-related behaviour. Aim: To explore the association between self-reported handwashing and a range of psychological variables in a sample of nurses in a large acute hospital. Results and discussion: Nurses in this study were more likely to wash their hands if they perceived it to be important and if they thought their workplace helped them in doing so. The best predictor of perceived importance was how strongly a nurse believed that poor handwashing practice contributes to spreading infection. Conclusion: In this study, psychological variables such as perception of importance, perception of workplace support, occupational stress and perception of risk were important predictors of handwashing behaviour.

Evaluation of Corrosion Fatigue Behaviour of Laser-welded NiTi Alloys using Bending Rotation Fatigue Test in Simulated Body Fluid

Shape memory NiTi alloys have been used extensively for medical device applications such as orthopedic, dental, vascular and cardiovascular devices on account of their unique shape memory effect (SME) and super-elasticity (SE). Laser welding is found to be the most suitable method used to fabricate NiTi-based medical components. However, the performance of laser-welded NiTi alloys under corrosive environments is not fully understood and a specific focus on understanding the corrosion fatigue behaviour is not evident in the literature. This study reveals a comparison of corrosion fatigue behaviour of laser-welded and bare NiTi alloys using bending rotation fatigue (BRF) test which was integrated with a specifically designed corrosion cell. The testing environment was Hanks’ solution (simulated body fluid) at 37.5oC. Electrochemical impedance spectroscopic (EIS) measurement was carried out to monitor the change of corrosion resistance at different periods during the BRF test. Experiments indicate that the laser-welded NiTi alloy would be more susceptible to the corrosion fatigue attack than the bare NiTi alloy. This finding can serve as a benchmark for the product designers and engineers to determine the factor of safety of NiTi medical devices fabricated using laser welding.

“They should stay at their desk until the work’s done”: a qualitative study examining perceptions of sedentary behaviour in a desk-based occupational setting

Background: Workplace sedentary behaviour is a priority target for health promotion. However, little is known about how to effect change. We aimed to explore desk-based office workers’ perceptions of factors that influenced sedentary behaviour at work and to explore the feasibility of using a novel mobile phone application to track their behaviours.

Methods: We invited office employees (n = 12) and managers (n = 2) in a software engineering company to participate in semi-structured interviews to explore perceived barriers and facilitators affecting workplace sedentary behaviour. We assessed participants’ sedentary behaviours using an accelerometer before and after they used a mobile phone application to record their activities at self-selected time intervals daily for 2 weeks. Interviews were analysed using a thematic framework.

Results: Software engineers (5 employees; 2 managers) were interviewed; 13 tested the mobile phone application; 8 returned feedback. Major barriers to reducing workplace sedentary behaviour included the pressure of ‘getting the job done’, the nature of their work requiring sitting at a computer, personal preferences for the use of time at and after work, and a lack of facilities, such as a canteen, to encourage moving from their desks. Facilitators for reduced sedentariness included having a definite reason to leave their desks, social interaction and relief of physical and mental symptoms of prolonged sitting. The findings were similar for participants with different levels of overall physical activity. Valid accelerometer data were tracked for four participants: all reduced their sedentary behaviour. Participants stated that recording data using the phone application added to their day’s work but the extent to which individuals perceived this as a burden varied and was counter-balanced by its perceived value in increasing awareness of sedentary behaviour. Individuals expressed a wish for flexibility in its configuration.

Conclusions: These findings indicate that employers’ and employees’ perceptions of the cultural context and physical environment of their work, as well as personal factors, must be considered in attempting to effect changes that reduce workplace sedentary behaviour. Further research should investigate appropriate individually tailored approaches to this challenge, using a framework of behaviour change theory which takes account of specific work practices, preferences and settings.

Behaviour-time budget and functional habitat use of a free-ranging European badger (Meles meles)

Background: The European badger (Melesmeles) is involved in the maintenance of bovine tuberculosis infection and onward spread to cattle. However, little is known about how transmission occurs. One possible route could be through direct contact between infected badgers and cattle. It is also possible that indirect contact between cattle and infected badger excretory products such as faeces or urine may occur either on pasture or within and around farm buildings. A better understanding of behaviour patterns in wild badgers may help to develop biosecurity measures to minimise direct and indirect contact between badgers and cattle. However, monitoring the behaviour of free-ranging badgers can be logistically challenging and labour intensive due to their nocturnal and semi-fossorial nature.We trialled a GPS and tri-axial accelerometer-equipped collar on a free-ranging badger to assess its potential value to elucidate behaviour-time budgets and functional habitat use. Results: During the recording period between 16:00 and 08:00 on a single night, resting was the most commonly identified behaviour (67.4%) followed by walking (20.9%), snuffling (9.5%) and trotting (2.3%).When examining accelerometer data associated with each GPS fix and habitat type (occurring 2 min 30 s before and after), walking was themost common behaviour in woodland (40.3%) and arable habitats (53.8%), while snuffling was themost common behaviour in pasture (61.9%). Several nocturnal resting periods were also observed. The total distance travelled was 2.28 km. Conclusions: In the present report, we demonstrate proof of principle in the application of a combined GPS and accelerometer device to collect detailed quantitative data on wild badger behaviour. Behaviour-time budgets allow us to investigate how badgers allocate energy to different activities and how thismight change with disease status. Such information could be useful in the development of measures to reduce opportunities for onward transmission of bovine tuberculosis from badgers to cattle.