Rapid and MR-Independent IK1 activation by aldosterone during ischemia-reperfusion

In ST elevation myocardial infarction (STEMI) context, clinical studies have shown the deleterious effect of high aldosterone levels on ventricular arrhythmia occurrence and cardiac mortality. Previous in vitro reports showed that during ischemia-reperfusion, aldosterone modulates K+ currents involved in the holding of the resting membrane potential (RMP). The aim of this study was to assess the electrophysiological impact of aldosterone on IK1 current during myocardial ischemia-reperfusion. We used an in vitro model of “border zone” using right rabbit ventricle and standard microelectrode technique followed by cell-attached recordings from freshly isolated rabbit ventricular cardiomyocytes. In microelectrode experiments, aldosterone (10 and 100 nmol/L, n=7 respectively) increased the action potential duration (APD) dispersion at 90% between ischemic and normoxic zones (from 95±4ms to 116±6 ms and 127±5 ms respectively, P<0.05) and reperfusion-induced sustained premature ventricular contractions occurrence (from 2/12 to 5/7 preparations, P<0.05). Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia). Furthermore, aldosterone induced a RMP hyperpolarization, evoking an implication of a K+ current involved in the holding of the RMP. Cell-attached recordings showed that aldosterone 10 nmol/L quickly activated (within 6.2±0.4 min) a 30 pS K+-selective current, inward rectifier, with pharmacological and biophysical properties consistent with the IK1 current (NPo =1.9±0.4 in control vs NPo=3.0±0.4, n=10, P<0.05). These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation. In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation

L'usage des systèmes d'informations électroniques en recherche scientifique : le cas de la neurophysiologie.

Nous présentons les premiers résultats d'une enquête destinée à mieux connaître les pratiques de recherche d'information bibliographique et documentaire chez les chercheurs scientifiques. 64 chercheurs et étudiants doctorants en neurophysiologie ont répondu à un questionnaire portant sur les méthodes, les outils, et les objectifs des recherches d'information typiques dans leur activité. De plus, 11 personnes parmi les répondants ont participé à un entretien individuel semi structuré. Il en ressort que l'usage d'outils informatisés de recherche d'information bibliographique (RIB) est désormais pratique courante, au détriment des index et autres sources imprimées. Les principaux outils utilisés sont la base de données bibliographiques PubMed et le moteur de recherche Google, avec toutefois de nombreux autres outils plus spécifiques utilisés à titre complémentaire. Les répondants mentionnent des objectifs très variés, comme l'acquisition de connaissances nouvelles, mais aussi la recherche de techniques expérimentales, la veille documentaire, l'alimentation du débat scientifique, ou l'aide à l'enseignement. Les difficultés que rencontrent les experts en neurosciences intégratives dans l'exploitation des outils informatiques de RIB spécialisés semblent surtout liées à l'absence de formation des experts à ces outils. Les chercheurs définissent l'outil informatique de RIB « idéal » comme fiable et exhaustif, mais aussi rapide et facile à utiliser et apprendre . De fait, le facteur temps apparaît déterminant dans leur choix d'utilisation ou non d'un outil particulier. Cette étude ouvre la voie à des expériences plus spécifiques, qui porteront sur les stratégies cognitives des experts dans ce type de tâches

Electron-impact ionization of atomic hydrogen at 2 eV above threshold

The convergent close-coupling method is applied to the calculation of fully differential cross sections for ionization of atomic hydrogen by 15.6 eV electrons. We find that even at this low energy the method is able to yield predictive results with small uncertainty. As a consequence we suspect that the experimental normalization at this energy is approximately a factor of two too high.Comment: 10 page

Possible common central pathway for resistin and insulin in regulating food intake.

Aim: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Methods: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1–0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Results: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. Conclusion:  The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS

Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart

Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility

An integrating factor matrix method to find first integrals

In this paper we developed an integrating factor matrix method to derive conditions for the existence of first integrals. We use this novel method to obtain first integrals, along with the conditions for their existence, for two and three dimensional Lotka-Volterra systems with constant terms. The results are compared to previous results obtained by other methods

18-month occurrence of severe events among early diagnosed HIV-infected children before antiretroviral therapy in Abidjan, Côte d'Ivoire: A cohort study

<p>Abstract</p> <p>Objective</p> <p>To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire.</p> <p>Methods</p> <p>Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001–2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995–2000), used as a reference group. HIV-infected pregnant women ≥ 32–36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV ± 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48–72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model.</p> <p>Results</p> <p>Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%–81%) and 77% in Ditrame (95%CI: 65%–89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3–1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2–11.2; p = 0.01).</p> <p>Conclusion</p> <p>Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.</p

Going beyond children’s single-text comprehension:The role of fundamental and higher–level skills in 4th graders’ multiple-document comprehension

Background: Children's comprehension of single texts relies on both foundational and higher-level skills. These are also assumed to support multiple-document comprehension, but their relative importance has not been examined, to date. Multiple-document comprehension additionally requires the identification and use of information about each document's source. Aims: This study examined multiple-document comprehension in primary school-aged children. It sought to determine the relative importance of skills proposed to be common to both single-text and multiple-document comprehension (word reading fluency, verbal working memory, comprehension monitoring) and specific to the latter (source use). Single-text comprehension and prior topic knowledge were considered as moderator and control. Sample: Participants were 94 children in the fourth year (mean age = 9; 7 years; 52% females). Methods: Children read three documents on each of two topics (chocolate and video games). Multiple-document comprehension and source use were assessed through short essays. Independent measures of the fundamental and higher-level skills were used. Results: There was a significant direct and indirect influence of word reading fluency on comprehension of multiple documents on videogames and also an indirect influence of comprehension monitoring. Indirect influences of word reading fluency and comprehension monitoring on multiple-document comprehension for both topics were also apparent. Verbal working memory was not a unique predictor. When source information was identified, it was included to support the argument in the composition. Conclusions: Efficient word reading, comprehension monitoring, and single-text comprehension are important for multiple-document comprehension in young readers. Implications of these findings and differences between the two document sets are discussed