Estrogen-related receptor α and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria

Mitochondrial biogenesis, which depends on nuclear as well as mitochondrial genes, occurs in response to increased cellular ATP demand. The nuclear transcriptional factors, estrogen-related receptor α (ERRα) and nuclear respiratory factors 1 and 2, are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis, whereas coactivators of the peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family serve as mediators between the environment and this machinery. In the context of proliferating cells, PGC-1-related coactivator (PRC) is a member of the PGC-1 family, which is known to act in partnership with nuclear respiratory factors, but no functional interference between PRC and ERRα has been described so far. We explored three thyroid cell lines, FTC-133, XTC.UC1 and RO 82 W-1, each characterized by a different mitochondrial content, and studied their behavior towards PRC and ERRα in terms of respiratory efficiency. Overexpression of PRC and ERRα led to increased respiratory chain capacity and mitochondrial mass. The inhibition of ERRα decreased cell growth and respiratory chain capacity in all three cell lines. However, the inhibition of PRC and ERRα produced a greater effect in the oxidative cell model, decreasing the mitochondrial mass and the phosphorylating respiration, whereas the nonphosphorylating respiration remained unchanged. We therefore hypothesize that the ERRα–PRC complex plays a role in arresting the cell cycle through the regulation of oxidative phosphorylation in oxidative cells, and through some other pathway in glycolytic cells

Linking epigenetics and biological conservation: Towards a conservation epigenetics perspective

International audience1. Biodiversity conservation is a global issue where the challenge is to integrate all levels of biodiversity to ensure the long-term evolutionary potential and resilience of biological systems. Genetic approaches have largely contributed to conservation biology by defining "conservation entities" accounting for their evolutionary history and adaptive potential, the so-called evolutionary significant units (ESUs). Yet, these approaches only loosely integrate the short-term ecological history of organisms. 2. Here, we argue that epigenetic variation, and more particularly DNA methylation, represents a molecular component of biodiversity that directly links the genome to the environment. As such, it provides the required information on the ecological background of organisms for an integrative field of conservation biology. 3. We synthesize knowledge about the importance of epigenetic mechanisms in (a) orchestrating fundamental development alternatives in organisms, (b) enabling individuals to respond in real-time to selection pressures and (c) improving ecosystem stability and functioning. 4. Using practical examples in conservation biology, we illustrate the relevance of DNA methylation (a) as biomarkers of past and present environmental stress events as well as biomarkers of physiological conditions of individuals; (b) for documenting the ecological structuring/clustering of wild populations and hence for better integrating ecology into ESUs; (c) for improving conservation transloca-tions; and (d) for studying landscape functional connectivity. 5. We conclude that an epigenetic conservation perspective will provide environmental managers the possibility to refine ESUs, to set conservation plans taking into account the capacity of organisms to rapidly cope with environmental changes, and hence to improve the conservation of wild populations. K E Y W O R D S conservation, DNA methylation, ecological timescales, epigenetic, evolutionary significant unit

Prevention of Ventricular Arrhythmias With Sarcoplasmic Reticulum Ca2+ ATPase Pump Overexpression in a Porcine Model of Ischemia Reperfusion

Background— Ventricular arrhythmias are life-threatening complications of heart failure and myocardial ischemia. Increased diastolic Ca2+ overload occurring in ischemia leads to afterdepolarizations and aftercontractions that are responsible for cellular electric instability. We inquired whether sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) overexpression could reduce ischemic ventricular arrhythmias by modulating Ca2+ overload.Methods and Results— SERCA2a overexpression in pig hearts was achieved by intracoronary gene delivery of adenovirus in the 3 main coronary arteries. Homogeneous distribution of the gene was obtained through the left ventricle. After gene delivery, the left anterior descending coronary artery was occluded for 30 minutes to induce myocardial ischemia followed by reperfusion. We compared this model with a model of permanent coronary artery occlusion. Twenty-four–hour ECG Holter recordings showed that SERCA2a overexpression significantly reduced the number of episodes of ventricular tachycardia after reperfusion, whereas no significant difference was found in the occurrence of sustained or nonsustained ventricular tachycardia and ventricular fibrillation in pigs undergoing permanent occlusion. Conclusions— We show that Ca2+ cycling modulation using SERCA2a overexpression reduces ventricular arrhythmias after ischemia-reperfusion. Strategies that modulate postischemic Ca2+ overload may have clinical promise for the treatment of ventricular arrhythmias

Minimising pain in farm animals: the 3S approach - ‘Suppress, Substitute, Soothe'

Recently, the French National Institute for Agricultural Research appointed an expert committee to review the issue of pain in food-producing farm animals. To minimise pain, the authors developed a ‘3S' approach accounting for ‘Suppress, Substitute and Soothe' by analogy with the ‘3Rs' approach of ‘Reduction, Refinement and Replacement' applied in the context of animal experimentation. Thus, when addressing the matter of pain, the following steps and solutions could be assessed, in the light of their feasibility (technical constraints, logistics and regulations), acceptability (societal and financial aspects) and availability. The first solution is to suppress any source of pain that brings no obvious advantage to the animals or the producers, as well as sources of pain for which potential benefits are largely exceeded by the negative effects. For instance, tail docking of cattle has recently been eliminated. Genetic selection on the basis of resistance criteria (as e.g. for lameness in cattle and poultry) or reduction of undesirable traits (e.g. boar taint in pigs) may also reduce painful conditions or procedures. The second solution is to substitute a technique causing pain by another less-painful method. For example, if dehorning cattle is unavoidable, it is preferable to perform it at a very young age, cauterising the horn bud. Animal management and constraint systems should be designed to reduce the risk for injury and bruising. Lastly, in situations where pain is known to be present, because of animal management procedures such as dehorning or castration, or because of pathology, for example lameness, systemic or local pharmacological treatments should be used to soothe pain. These treatments should take into account the duration of pain, which, in the case of some management procedures or diseases, may persist for longer periods. The administration of pain medication may require the intervention of veterinarians, but exemptions exist where breeders are allowed to use local anaesthesia (e.g. castration and dehorning in Switzerland). Extension of such exemptions, national or European legislation on pain management, or the introduction of animal welfare codes by retailers into their meat products may help further developments. In addition, veterinarians and farmers should be given the necessary tools and information to take into account animal pain in their management decision

La production biologique de porcs en Europe - Gestion de la santé des porcs dans les élevages de production

Les éleveurs de porcs biologiques ont développé en Europe différents systèmes de logement qui dépendent de la disponibilité des terres, des caractéristiques du sol et du climat, des traditions et des schémas de certification. Ce guide décrit les principaux systèmes de logement des porcs biologiques. Il compare les avantages et les inconvénients de chacun et donne des recommandations aux éleveurs pour mieux agir sur la santé des animaux

Reliability of the CARE rule and the HEART score to rule out an acute coronary syndrome in non-traumatic chest pain patients

In patients consulting in the Emergency Department for chest pain, a HEART score ≤ 3 has been shown to rule out an acute coronary syndrome (ACS) with a low risk of major adverse cardiac event (MACE) occurrence. A negative CARE rule (≤ 1) that stands for the first four elements of the HEART score may have similar rule-out reliability without troponin assay requirement. We aim to prospectively assess the performance of the CARE rule and of the HEART score to predict MACE in a chest pain population. Prospective two-center non-interventional study. Patients admitted to the ED for non-traumatic chest pain were included, and followed-up at 6 weeks. The main study endpoint was the 6-week rate of MACE (myocardial infarction, coronary angioplasty, coronary bypass, and sudden unexplained death). 641 patients were included, of whom 9.5% presented a MACE at 6 weeks. The CARE rule was negative for 31.2% of patients, and none presented a MACE during follow-up [0, 95% confidence interval: (0.0–1.9)]. The HEART score was ≤ 3 for 63.0% of patients, and none presented a MACE during follow-up [0% (0.0–0.9)]. With an incidence below 2% in the negative group, the CARE rule seemed able to safely rule out a MACE without any biological test for one-third of patients with chest pain and the HEART score for another third with a single troponin assay

TRα Mutations in Human

Resistance to thyroid hormone alpha is an emerging syndrome, with up to now a limited number of published cases. Some features are common to most of the patients, but there is still some work to provide a comprehensive description of the full spectrum of the syndrome. A survey of the strategy to screen for and characterize the mutations in TR α gene is given