Phosphoproteomic analysis identifies supervillin as an ERK3 substrate regulating cytokinesis and cell ploidy

Extracellular signal-regulated kinase 3 (ERK3) is a poorly characterized member of the mitogen-activated protein (MAP) kinase family. Functional analysis of the ERK3 signaling pathway has been hampered by a lack of knowledge about the substrates and downstream effectors of the kinase. Here, we used large-scale quantitative phosphoproteomics and targeted gene silencing to identify direct ERK3 substrates and gain insight into its cellular functions. Detailed validation of one candidate substrate identified the gelsolin/villin family member supervillin (SVIL) as a bona fide ERK3 substrate. We show that ERK3 phosphorylates SVIL on Ser245 to regulate myosin II activation and cytokinesis completion in dividing cells. Depletion of SVIL or ERK3 leads to increased cytokinesis failure and multinucleation, a phenotype rescued by wild type SVIL but not by the non-phosphorylatable S245A mutant. Our results unveil a new function of the atypical MAP kinase ERK3 in cell division and the regulation of cell ploidy

Comorbidities of COPD

International audienceBy 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately. Extrapulmonary comorbidities are common in COPD and influence prognosis; we propose an exhaustive comorbidities revie

Enquête observationnelle sur les pneumonies aiguës communautaires dans le département des maladies respiratoires du Centre Hospitalier du Mans

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Tuning of the Ba5Nb4O15 permittivity temperature coefficient

International audienc

Tuning of the Ba5Nb4O15 permittivity temperature coefficient

International audienc

Importance of the Conditioning of the Chitosan Support in a Catalyst-Containing Ionic Liquid Phase Immobilised on Chitosan: The Palladium-Catalysed Allylation Reaction Case

International audienc

Importance of the Conditioning of the Chitosan Support in a Catalyst-Containing Ionic Liquid Phase Immobilised on Chitosan: The Palladium-Catalysed Allylation Reaction Case

International audienc

Les comorbidités dans la BPCO

International audienc

Les comorbidités dans la BPCO [Comorbidities of COPD]

National audienceRésumé La BPCO est une maladie respiratoire chronique lentement évolutive caractérisée par une diminution non complètement réversible des débits aériens. L’agent causal principal est le tabagisme. La BPCO est un problème de santé publique qui se traduit par une morbidité, un handicap et une mortalité élevés. Une de ses caractéristiques est la place que prennent les comorbidités en raison du vieillissement, des facteurs de risque et de facteurs génétiques. Les patients ayant plus de 2 comorbidités représentent 26 % de la population mais plus de la moitié des coûts de traitements. Nous passons en revue les différentes comorbidités (cardiovasculaires, l’ostéoporose, la dénutrition, l’obésité, le sujet âgé, l’anémie, les troubles du sommeil, le diabète et syndrome métabolique, l’anxiété-dépression ou le cancer broncho-pulmonaire) avec leur physiopathologie, prévalence mais aussi leur impact sur le pronostic de la BPCO. En effet, la présence de l’une ou plusieurs de ces comorbidités en altèrent le pronostic. Nous sommes donc confrontés à la question de la multimorbidité et à la difficulté de l’approche pratique et pertinente de la gestion de ces comorbidités. De plus en plus, l’intérêt thérapeutique d’une prise en charge globale des comorbidités par une équipe multidisciplinaire est souligné sans perdre de vue l’essentiel : à savoir le sevrage tabagique. Summary COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patient

First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

The development of antiangiogenic treatments, followed by immune checkpoint inhibitors (ICI), has significantly changed the management of metastatic clear cell renal cell cancer. Several phase III trials show the superiority of combination therapy, dual immunotherapy (ICI-ICI) or ICI plus tyrosine kinase inhibitors (TKI) of the vascular endothelium growth factor (VEGF) over sunitinib monotherapy. The question is therefore what is the best combination for a given patient? A strategy based on the International Metastatic Database Consortium (IMDC) classification is currently recommended with pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab (for all patients) or nivolumab + ipilimumab (for patients with intermediate or poor risk), which are the first-line treatment standards of care. However, several issues remain unresolved and require further investigation, such as the PD-L1 status, the relevance of possible options based on the patient’s profile, and consideration of second-line and subsequent treatments