Mechanisms of Na+-Ca2+ Exchange Inhibition by Amphiphiles in CardiacMyocytes: Importance of Transbilayer Movement

The membrane lipid environment and lipid signaling pathways are potentially involved in the modulation of the activity of the cardiac Na+-Ca2+ exchanger (NCX). In the present study biophysical mechanisms of interactions of amphiphiles with the NCX and the functional consequences were examined. For this purpose, intracellular Ca2+ concentration jumps were generated by laser-flash photolysis of caged Ca2+ in guinea-pig ventricular myocytes and Na+-Ca2+ exchange currents (INa/Ca) were recorded in the whole-cell configuration of the patch-clamp technique. The inhibitory effect of amphiphiles increased with the length of the aliphatic chain between C7 and C10 and was more potent with cationic or anionic head groups than with uncharged head groups. Long-chain cationic amines (C12) exhibited a cut-off in their efficacy in INa/Ca inhibition. Analysis of the time-course, comparison with the Ni2+-induced INa/Ca block and confocal laser scanning microscopy experiments with fluorescent lipid analogs (C6- and C12-NBD-labeled analogs) suggested that amphiphiles need to be incorporated into the membrane. Furthermore, NCX block appears to require transbilayer movement of the amphiphile to the inner leaflet ("flip”). We conclude that both, hydrophobic and electrostatic interactions between the lipids and the NCX may be important factors for the modulation by lipids and could be relevant in cardiac diseases where the lipid metabolism is altere

A conceptual glacio-hydrological model for high mountainous catchments

International audienceIn high mountainous catchments, the spatial precipitation and therefore the overall water balance is generally difficult to estimate. The present paper describes the structure and calibration of a semi-lumped conceptual glacio-hydrological model for the joint simulation of daily discharge and annual glacier mass balance that represents a better integrator of the water balance. The model has been developed for climate change impact studies and has therefore a parsimonious structure; it requires three input times series ? precipitation, temperature and potential evapotranspiration ? and has 7 parameters to calibrate. A multi-signal approach considering daily discharge and ? if available ? annual glacier mass balance has been developed for the calibration of these parameters. The model has been calibrated for three different catchments in the Swiss Alps having glaciation rates between 37% and 52%. It simulates well the observed daily discharge, the hydrological regime and some basic glaciological features, such as the annual mass balance

Mitigation and Adaptation Strategies – Organic Agriculture

This psoter presents information on the following - The concept of organic farming in the context of climate change - Carbon sequestration on organic farms - Consequences of an area-wide conversion to organic agricultur

A call for innovations tht change the (organic) world

Recent developments in organic farming and consumption show dynamic growth in markets; new uptake of Organic Agriculture by farmers, however, has been slow. Hindrances appear to be production problems or lack of trust by the farmers that organic methods can solve farming problems, such as fertilization, plant protection, animal health, efficient use of workforce, marketing diversity etc. While in some cases those problems can be solved through learning existing and regionally practiced methods, innovations are imperative to make organic farming competitive and a viable alternative farming system. OFIA, the Organic Farming Innovation Award, part of the Organic World Congress, highlights outstanding innovations and publishes priorities for innovative research

Long-term follow-up and residual sequelae after treatment for intracerebral germ-cell tumour in children and adolescents

Background: Information on long-term follow-up of children and adolescents treated for intracerebral germ-cell tumour is scant. We report on the results of a small series of patients treated at a single institution. Patients and methods: Hospital records from 15 patients treated between 1980 and 1998 were reviewed. An attempt was made to correlate sequelae to tumour location and treatment modalities. Results: This cohort constitutes 5.5% of all brain tumours diagnosed at our institution. Histology: 10 germinomas, 2 benign teratomas, 2 malignant teratomas, and one mixed germ-cell tumour. Overall survival was 87%, with a mean follow-up time of 7 years and 8 months. The majority of patients have long-term sequelae involving one or several organ systems. In 66% endocrine, in 47% ophthalmologic, in 60% neuropsycho-logical defects were observed. Endocrine and ophthalmologic sequelae show a correlation to tumour location. Neuropsycho-logical long-term abnormalities are frequent and are associated with cranial irradiation in particular at young age, but less with tumour location, irradiation dose or surgery. Conclusions: Our preliminary data suggest that today intracerebral germinomas and mature teratomas have a good prognosis even when a relapse occurs. The outcome for mixed germ-cell tumours and malignant teratomas is less favourable. Although long-term sequelae are present in the majority of patients, there is some evidence that patients treated after 1990 suffer fewer severe long-term defects, thereby indicating that recent treatment protocols may result in a reduction of sequela

Disseminated Fusarium oxysporum Infection in Hemophagocytic Lymphohistiocytosis

Abstract : The portal of entry of disseminated Fusarium spp. infections is still not clearly defined. We report on a disseminated Fusarium oxysporum infection occurring during a long period of severe neutropenia in a child with hemophagocytic lymphohistiocytosis. A nasogastric feeding tube was the possible source of entry of the fungu

Priority themes for swiss sustainability research

With this report, the Swiss Academies of Arts and Sciences contribute to achieving the SDGs: With a view to meeting Switzerland‘s commitments under the 2030 Agenda as a whole, it identifies our country‘s most urgent research needs

EHEC – kein spezifisches Problem nachhaltiger Landwirtschaft - [EHEC – A problem not specific to sustainable agriculture] [La EHEC – no es un problema específico de la agricultura sostenible] - [EHEC – Non è un problema specifi-co dell’agricoltura biologica] - [ECEH n’est pas un problème dû à l’agriculture durable] - [EHEC – nem speciálisan a fenntartható mezőgazdaság gondja] - [ECEH n’est pas un problème dû à l’agriculture durable]

DEUTSCH Über den EHEC-Erreger, der in Deutschland zu über dreissig tragischen Todesfällen geführt hat, ist viel spekuliert worden. Unterdessen konnten die Verbreitungswege nahezu aufgeklärt werden, während die Entstehung des Krankheitserregers noch weitgehend unklar ist. Im Zusammenhang mit dem EHEC-Ausbruch wurde auch die Frage erörtert, ob bestimmte Landwirtschaftsmethoden (zum Beispiel gemischte Betriebe mit Tierhaltung und Pflanzenbau oder die organische Düngung von Gemüse) oder ob gewisse Hygienisierungsmethoden für frische, konsumfähige Produkte(wie zum Beispiel die Verwendung von schonenden, weniger Rückstände verursachenden organischen Säuren) das Risiko erhöhen könnten. Diese Dokumentation geht nicht auf die aktuellen Fälle von EHEC in Norddeutschland ein, sondern liefert an diesem Beispiel Hintergrundinformationen zur Frage, wie nachhaltige, in Kreisläufen arbeitende Landwirtschaftsmethoden mit vom Tier auf den Menschen übertragbare Krankheitserreger (Zoonosen) umgehen. ENGLISH There has been much speculation about the pathogenic EHEC bacterial strain that has tragically claimed the lives of more than 30 people so far in Germany. Meanwhile, the transmission pathways have for the most part been identified. The origin of the pathogen, however, is largely unclear. In the context of the EHEC outbreak there have been debates as to whether certain agriculturalmethods (e.g. mixed holdings including both livestock and crop production, or the use of organic fertilizers for vegetable production) or certain sanitization methods for fresh consumable products (such as the use of organic acids, a mild treatment that leaves fewer residues) may increase the risk of infection. This document does not address the current epidemiological situation of the outbreak in northern Germany. Its purpose is rather to provide background information on the question of how sustainable agricultural methods based on nutrient cycling deal with pathogens that can be transmitted from animals to humans (zoonoses). CASTELLANO Mucho se ha especulado sobre la bacteria patógena Escherichia coli enterohemorrágica (ECEH), que ha ocasionado más de treinta muertes trágicas en Alemania. Hasta ahora casi se ha podido esclarecer la via de su propagación, mientras que sigue estando poco claro como ha aparecido el agente patógeno. Con el brote de la ECEH se ha cuestionado si determinadas prácticas agrícolas (por ejemplo, mantener explotaciones mixtas con ganado y cultivos, o la fertilización orgánica de los vegetales) o si los métodos de higiene para productos frescos, listos para el consumo (como por ejemplo, el uso de ácidos orgánicos menos agresivos y con menor riesgo de dejar residudos), pudieran incrementar los riesgos. Esta documento no se refiere sólo a los casos actuales de ECEH en el norte de Alemania, sino que proporciona, información básica de fondo, aprovechando este ejemplo, sobre como los métodos de producción agraria de ciclos cerrados con animales evitan forma sostenible que los patógenos generadores de enfermedades contagiosas (zoonosis) trasmisibles al ser humano. ITALIANO A proposito dell’insorgenza di EHEC è stata sollevata la questione se determinati metodi agricoli (per esempio aziende miste con allevamento di animali e produzione vegetale o la concimazione organica di ortaggi) oppure se determinati metodi di igienizzazione per pro-dotti freschi adatti al consumo (come per esempio l’impiego di acidi organici che provocano meno residui) possano aumentare i rischi. La presente documentazione non entra nei particolari degli attuali casi di EHEC nella Ger-mania settentrionale bensì fornisce informazioni d’approfondimento su come i me-todi agri-coli sostenibili basati sui cicli degli elementi nutritivi trattano la questione degli agenti pato-geni trasmissibili dagli animali all’uomo (zoonosi). HUNGARIAN Sok a spekuláció az EHEC kórokozót illetően, amely Németországban harmincnál is több tragikus halálesethez vezetett. Időközben a terjedés útját már csaknem teljesen felderítették, míg a kórokozó létrejöttéről még szinte semmit sem tudunk. Az EHEC fertőzés kitörése kapcsán az a kérdés is felmerült, hogy bizonyos mezőgazdasági módszerek (pl. a vegyes üzemek, melyek egyaránt foglalkoznak növénytermesztéssel és állattenyésztéssel, vagy a zöldségek szerves trágyázása), ill. a friss, fogyasztásra kész termékek egyes fertőtlenítési módszerei (így pl. a kímélőbb, kevesebb hulladékot eredményező szerves savak alkalmazása) nem növelhetik-e a kockázatot. A jelen tanulmány nem a Németország északi részén kialakult aktuális EHEC esetekkel foglalkozik, hanem háttér-információval szolgál arról, hogy a körforgásos működésű, fenntartható mezőgazdasági módszerek milyen kapcsolatban lehetnek az állatról emberre terjedő betegségekkel, az ún. zoonózisokkal. FRANCAIS ECEH n’est pas un problème dû à l’agriculture durabl

Comparative efficacy of long-acting bronchodilators for COPD - a network meta-analysis

Background: Clinicians are faced with an increasingly difficult choice regarding the optimal bronchodilator for patients with chronic obstructive pulmonary disease (COPD) given the number of new treatments. The objective of this study is to evaluate the comparative efficacy of indacaterol 75/150/300 μg once daily (OD), glycopyrronium bromide 50 μg OD, tiotropium bromide 18 μg/5 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for moderate to severe COPD. Methods: Forty randomized controlled trials were combined in a Bayesian network meta-analysis. Outcomes of interest were trough and post-dose forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) score and responders (≥4 points), and Transition Dyspnea Index (TDI) score and responders (≥1 point) at 6 months. Results: Indacaterol was associated with a higher trough FEV1 than other active treatments (difference for indacaterol 150 μg and 300 μg versus placebo: 152 mL (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the greatest improvement in SGRQ score (difference for indacaterol 150 μg and 300 μg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)). Glycopyrronium and tiotropium 18 μg resulted in the next best estimates for both outcomes with minor differences (difference for glycopyrronium versus tiotropium for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92). Conclusion: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium, and tiotropium are expected to be the most effective bronchodilators