Fungal X-Intrinsic Protein Aquaporin from Trichoderma atroviride: Structural and Functional Considerations

The major intrinsic protein (MIP) superfamily is a key part of the fungal transmembrane transport network. It facilitates the transport of water and low molecular weight solutes across biomembranes. The fungal uncharacterized X-Intrinsic Protein (XIP) subfamily includes the full protein diversity of MIP. Their biological functions still remain fully hypothetical. The aim of this study is still to deepen the diversity and the structure of the XIP subfamily in light of the MIP counterparts-the aquaporins (AQPs) and aquaglyceroporins (AQGPs)-and to describe for the first time their function in the development, biomass accumulation, and mycoparasitic aptitudes of the fungal bioagent Trichoderma atroviride. The fungus-XIP Glade, with one member (TriatXIP), is one of the three clades of MIPs that make up the diversity of T. atroviride MIPs, along with the AQPs (three members) and the AQGPs (three members). TriatXIP resembles those of strict aquaporins, predicting water diffusion and possibly other small polar solutes due to particularly wider ar/R constriction with a Lysine substitution at the LE2 position. The XIP loss of function in Delta TriatXIP mutants slightly delays biomass accumulation but does not impact mycoparasitic activities. Delta TriatMIP forms colonies similar to wild type; however, the hyphae are slightly thinner and colonies produce rare chlamydospores in PDA and specific media, most of which are relatively small and exhibit abnormal morphologies. To better understand the molecular causes of these deviant phenotypes, a wide-metabolic survey of the ATriatXIPs demonstrates that the delayed growth kinetic, correlated to a decrease in respiration rate, is caused by perturbations in the pentose phosphate pathway. Furthermore, the null expression of the XIP gene strongly impacts the expression of four expressed MIP-encoding genes of T. atroviride, a plausible compensating effect which safeguards the physiological integrity and life cycle of the fungus. This paper offers an overview of the fungal XIP family in the biocontrol agent T. atroviride which will be useful for further functional analysis of this particular MIP subfamily in vegetative growth and the environmental stress response in fungi. Ultimately, these findings have implications for the ecophysiology of Trichoderma spp. in natural, agronomic, and industrial systems

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this networ

Development and external validation of predictive models for prevalent and recurrent atrial fibrillation:a protocol for the analysis of the CATCH ME combined dataset

Background: Atrial fibrillation (AF) is caused by different mechanisms but current treatment strategies do not target these mechanisms. Stratified therapy based on mechanistic drivers and biomarkers of AF have the potential to improve AF prevention and management outcomes. We will integrate mechanistic insights with known pathophysiological drivers of AF in models predicting recurrent AF and prevalent AF to test hypotheses related to AF mechanisms and response to rhythm control therapy. Methods: We will harmonise and combine baseline and outcome data from 12 studies collected by six centres from the United Kingdom, Germany, France, Spain, and the Netherlands which assess prevalent AF or recurrent AF. A Delphi process and statistical selection will be used to identify candidate clinical predictors. Prediction models will be developed in patients with AF for AF recurrence and AF-related outcomes, and in patients with or without AF at baseline for prevalent AF. Models will be used to test mechanistic hypotheses and investigate the predictive value of plasma biomarkers. Discussion: This retrospective, harmonised, individual patient data analysis will use information from 12 datasets collected in five European countries. It is envisioned that the outcome of this analysis would provide a greater understanding of the factors associated with recurrent and prevalent AF, potentially allowing development of stratified approaches to prevention and therapy management

J Clin Invest

Arterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPN). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPN suggests that vascular function is altered. Consequences of JAK2V617F mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from Jak2V617F mice, resulting from disturbed endothelial nitric oxide pathway and increased endothelial oxidative stress. This response was reproduced in wild-type mice by circulating microvesicles isolated from patients carrying JAK2V617F and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from JAK2V617F erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for microvesicles effect. Myeloperoxidase inhibition in microvesicles derived from JAK2V617F erythrocytes supressed their effect on oxidative stress. Antioxidants, such as simvastatin and N-acetyl-cysteine, improved arterial dysfunction in Jak2V617F mice. In conclusion, JAK2V617F MPN are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears as promising therapeutic strategy in this setting

A roadmap to improve the quality of atrial fibrillation management:proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

Epicardial progenitors are source of adipocytes in human atria

International audienceno abstrac

Progression of wheat Tan spot under different bioclimatic stages and agricultural practices

Tan spot, caused by Pyrenophora tritici-repentis, is a severe worldwide wheat foliar disease and has become common in Tunisia. Two hundred wheat field surveys were conducted in northern Tunisia during the 2017-2019 seasons to determine disease intensity and the correlation of the tan spot with agricultural practices and environmental factors. The disease infested 67% of the visited regions. The highest prevalence (87.5%), incidence (> 30%), and severity (> 10%) were observed in sub-humid regions, contrary to the middle semi-arid regions. Logistic regression was used to analyse the correlation of incidence and severity with various factors as independent variables. In a multiple variable model, the bioclimatic stages, variety, previous crop, humidity, and rainfall were significantly associated with tan spot incidence and severity. High incidence and severity were significantly correlated to the sub-humid regions, varieties Maâli, Razzak, Karim, and Carioca, rainfall, high level of humidity, and monoculture. The correlation between the tan spot and several environmental factors must be considered to ensure successful and sustainable disease management strategies