Remote Ischemic Conditioning Influences Mitochondrial Dynamics

Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission. Interventions that decrease mitochondrial fission or increase mitochondrial fusion have been associated with reduced I/R injury. However, whether RIPC influences mitochondrial dynamics or not has yet to be ascertained.We sought to determine the role played by mitochondrial dynamics in RIPC-induced cardioprotection. Male adult rats exposed in vivo to myocardial I/R were assigned to one of two groups, either undergoing 40 min of myocardial ischemia followed by 120 min of reperfusion (MI group) or four 5-min cycles of limb ischemia interspersed by 5 min of limb reperfusion, immediately prior to myocardial ischemia and 120 min of reperfusion (MI+RIPC group). After reperfusion, infarct size was assessed and myocardial tissue was analyzed by Western blot and electron microscopy. RIPC induced smaller infarct size (-28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology. These findings suggest that mitochondrial dynamics play a role in the mechanisms of RIPC-induced cardioprotection

Role of hypoxia inducible factor-1α in remote limb ischemic preconditioning.

Remote ischemic preconditioning (RIPC) has emerged as a feasible and attractive therapeutic procedure for heart protection against ischemia/reperfusion (I/R) injury. However, its molecular mechanisms remain poorly understood. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that plays a key role in the cellular adaptation to hypoxia and ischemia. This study\u27s aim was to test whether RIPC-induced cardioprotection requires HIF-1α upregulation to be effective. In the first study, wild-type mice and mice heterozygous for HIF1a (gene encoding the HIF-1α protein) were subjected to RIPC immediately before myocardial infarction (MI). RIPC resulted in a robust HIF-1α activation in the limb and acute cardioprotection in wild-type mice. RIPC-induced cardioprotection was preserved in heterozygous mice, despite the low HIF-1α expression in their limbs. In the second study, the role of HIF-1α in RIPC was evaluated using cadmium (Cd), a pharmacological HIF-1α inhibitor. Rats were subjected to MI (MI group) or to RIPC immediately prior to MI (R-MI group). Cd was injected 18 0min before RIPC (Cd-R-MI group). RIPC induced robust HIF-1α activation in rat limbs and significantly reduced infarct size (IS). Despite Cd\u27s inhibition of HIF-1α activation, RIPC-induced cardioprotection was preserved in the Cd-R-MI group. RIPC applied immediately prior to MI increased HIF-1α expression and attenuated IS in rats and wild-type mice. However, RIPC-induced cardioprotection was preserved in partially HIF1a-deficient mice and in rats pretreated with Cd. When considered together, these results suggest that HIF-1α upregulation is unnecessary in acute RIPC

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

Long-term prognostic significance of right bundle-branch morphology ventricular ectopy induced during stress test in patients with intermediate to high probability of coronary artery disease

Aims: Stress-induced right bundle-branch block morphology ventricular ectopy (SI-RBVE) may be caused by left ventricular myocardial anomalies. While frequent ventricular ectopy (FVE) has been linked to poor outcomes, the prognostic value of SI-RBVE has not been established. The study aims to determine whether SI-RBVE is associated with increased mortality. Methods and results: Three hundred forty-three patients with an intermediate to high probability of coronary artery disease were prospectively included. Patients were referred for a single-photon emission computed tomography and underwent a stress test according to standard protocols. Stress-induced right bundle-branch block morphology ventricular ectopy (VE) was defined as one or more induced premature beats with positive predominance in V1. Frequent VE was defined as the presence of seven or more ventricular premature beats per minute or any organized ventricular arrhythmia. During a mean follow-up of 4.5 ± 1.3 years, 59 deaths occurred. The death rate was higher in the SI-RBVE group (23.4% vs. 14.0%, P = 0.021). Age [odds ratio (OR) = 1.09 (95% CI: 1.06-1.13), P < 0.001] and peripheral artery disease [OR = 2.47 (95% CI: 1.35-4.50) P = 0.003] were independent factors of mortality, but single-photon emission computed tomography findings were not. There was an interaction between SI-RBVE and left ventricular ejection fraction (LVEF). In patients with LVEF > 50%, SI-RBVE was an incremental risk factor for mortality [OR = 2.83 (95% CI: 1.40-5.74), P = 0.004]. Stress-induced right bundle-branch block morphology VE patients also presented higher rates of known coronary artery disease, ischaemia, scar, and ST-segment changes. Frequent VE was not related to mortality. Conclusion: Stress-induced right bundle-branch block morphology VE is associated with an increased mortality in patients with preserved LVEF

Adaptive Evolution of Staphylococcus aureus during Chronic Endobronchial Infection of a Cystic Fibrosis Patient

The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections

Disabled-2 (Dab2) inhibits Wnt/β-catenin signalling by binding LRP6 and promoting its internalization through clathrin

Wnt signalling requires caveolin-dependent endocytic uptake of the Fz/LRP6 receptor complex. The tumour suppressor Disabled-2 inhibits Wnt signalling by sequestering CK2-phosphorylated LRP6 into an alternative clathrin-dependent endocytic pathway

Understanding the political motivations that shape Rwanda’s emergent developmental state

Twenty years after its horrific genocide, Rwanda has become a model for economic development. At the same time, its government has been criticized for its authoritarian tactics and use of violence. Missing from the often-polarized debate are the connections between these two perspectives. Synthesizing existing literature on Rwanda in light of a combined year of fieldwork, we argue that the GoR is using the developmental infrastructure to deepen state power and expand political control. We first identify the historical pressures that have motivated the Rwanda Patriotic Front (RPF) to re-imagine the political landscape. Sectarian unrest, political rivalry, wider regional insecurity, and aid withdrawal have all pressured the RPF to identify growth as strategic. However, the country’s political transformation extends beyond a prioritisation of growth and encompasses the reordering of the social and physical layout of the territory, the articulation of new ideologies and mindsets, and the provision of social services and surveillance infrastructure. Growth and social control go hand in hand. As such, the paper’s main contribution is to bring together the two sides of the Rwandan debate and place the country in a broader sociological literature about the parallel development of capitalist relations and transformations in state power

Der Verbleib kupferbasierter Fungizide in Weinbergböden: Eine Fallstudie der stabilen Kupfer-Isotopenverhältnisse und Elektronenspinresonanz von Calco- und Vertisolen in Soave (Italien)

Kupferbasierte Fungizide sind im Weinbau weit verbreitet und im biologischen Weinbau die einzig erlaubten Pestizide zur Bekämpfung von falschem Mehltau. Durch den intensiven, dauerhaften Gebrauch von Kupfer reichert sich dieser, mit wachsenden ökotoxikologischen Konsequenzen, in Weinbergböden an. In dieser Studie untersuchen wir den Verbleib von Kupfer in einem Calcosol und einem Vertisol aus Soave (Italien). Beide Böden werden seit über 50 Jahren mit Kupfer behandelt. Wir stellen Massenbilanzen auf und nutzen die innovative Kombination aus Messung stabiler Cu-Isotopenverhältnisse und Elektronenspinresonanzspektroskopie (ESR), um Einblicke in die biogeochemischen Mechanismen der Kupferbindung zu erlangen. Die untersuchten Böden weisen hohe exogene Kupfergehalte auf, welche eine Akkumulation der heutigen maximalen Behandlungsmenge über 50 Jahre überschreiten. Dies belegt, dass einmal sehr viel größere Mengen Cu im Weinbau verwendet wurden und dass ein Großteil dieses Kupfers in den jeweiligen Böden verbleibt. In Vertisolen fallen die Cu-Konzentrationen unter dem vertischen Horizont schnell auf die geogene Hintergrundkonzentration, wobei in Calcosolen dieser Abfall progressiver erfolgt. Isotopenverhältnisse unterscheiden sich zwischen den verschieden Bodentypen (δCu-65 zwischen 0.12 und 0.37 ‰), obwohl sie die gleiche Behandlung erfahren haben. Kupferisotope in Oberböden sind schwerer als in Unterböden und Citratextraktionen zeigen, dass mobiles Kupfer isotopisch schwerer ist als der Gesamtgehalt. Die Horizonte des Calcosols sind systematisch leichter als die des Vertisols, was auf unterschiedliche biogeochemische Bindungsmechanismen von Kupfer hinweist. Dies wird durch die ESR-Spektren bestätigt. In Oberböden zeigen sie eine Kupferbindung an organisches Material, wobei es im gesamten Bodenprofil Unterschiede in der Cu-Bindung zwischen den beiden Bodentypen gibt. Wenn jedoch Horizonte des Calcosols mit Säure entkalkt werden, nähren sich deren ESR-Spektren denen der Vertisole an, wohingegen letztere nicht auf eine Säurebehandlung reagieren. Somit wird gezeigt, dass in Calcosolen Karbonate an der Bindung von Kupfer beteiligt sind wobei in Vertisolen der vertische Horizont eine wichtige Rolle spielt. Darüber hinaus wird durch die analoge Variation von ESR-Spektren und Isotopenverhältnissen wird die Anwendbarkeit von Cu-Isotopenanalysen und ESR-Spektroskopie zur Aufklärung von biogeochemischen Prozessen in Böden demonstriert