Interaction entre les macrophages et le virus de la choriomeningite lymphocytaire

SIGLET 54369 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Transgenic plants that express genes including the untranslated region of the turnip yellow mosaic virus (TYMV) genome are partially protected against TYMV infection

International audienc

Sensori-motor Learning With Movement Sonification: A Perspective From Recent Interdisciplinary Studies

This article reports on an interdisciplinary research project on movement sonification for sensori-motor learning. First, we describe different research fields which have contributed to movement sonification, from music technology including gesture-controlled sound synthesis, sonic interaction design, to research on sensori-motor learning with auditory-feedback. In particular, we propose to distinguish between sound-oriented tasks and movement-oriented tasks in experiment involving interactive sound feedback.We describe several research questions and recently published results on movement control, learning and perception. In particular, we studied the effect of the auditory feedback on movements considering several cases: from experiments on pointing and visuo-motor tracking to more complex tasks where interactive sound feedback can guide movements, or cases of sensory substitution where the auditory feedback can inform on object shapes. We also developed specific methodologies and technologies for designing the sonic feedback and movement sonification. We conclude with a discussion on key future research challenges in sensori-motor learning with movement sonification. We also point out towards promising applications such as rehabilitation, sport training or product design

Deciphering the internal complexity of living cells with quantitative phase microscopy: a multiscale approach

The distribution of refractive indices (RIs) of a living cell contributes in a nonintuitive manner to its optical phase image and quite rarely can be inverted to recover its internal structure. The interpretation of the quantitative phase images of living cells remains a difficult task because (1) we still have very little knowledge on the impact of its internal macromolecular complexes on the local RI and (2) phase changes produced by light propagation through the sample are mixed with diffraction effects by the internal cell bodies. We propose to implement a two-dimensional wavelet-based contour chain detection method to distinguish internal boundaries based on their greatest optical path difference gradients. These contour chains correspond to the highest image phase contrast and follow the local RI inhomogeneities linked to the intracellular structural intricacy. Their statistics and spatial distribution are the morphological indicators suited for comparing cells of different origins and/ or to follow their transformation in pathologic situations. We use this method to compare nonadherent blood cells from primary and laboratory culture origins and to assess the internal transformation of hematopoietic stem cells by the transduction of the BCR-ABL oncogene responsible for the chronic myelogenous leukemia. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE

Efficacy and Safety of Erythropoietic-Stimulating Agents with Ruxolitinib in Myelofibrosis Patients : A Retrospective Analysis on 45 Patients. on Behalf of the French Intergroup of Myeloproliferative Disorders (FIM)

58th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), San Diego, CA, DEC 03-06, 2016International audienceBackgroundRuxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms in patients (pts) with primary myelofibrosis (PMF), post-polycythemia vera-MF (PPV-MF), and post-essential thrombocythemia-MF (PET-MF). Anemia is another frequent issue in MF, which may be managed by the use of ESA, leading to a 40-50% response rate in small studies. Consistent with its JAK2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need, especially during the first 12-24 weeks of treatment in the COMFORT studies.Despite potential antagonistic mechanisms of action on JAK2, some responses on anemia have been reported with the addition of ESA to ruxolitinib in a small subset of pts in the COMFORT II study. The present study aimed to better assess the efficacy of ESA on anemia related to ruxolitinib and tolerance of this combination in a larger cohort of pts treated for MF in general practice.MethodsWe performed an observational study on patients with MF previously or currently treated with concomitant ESA and Ruxolitinib in French centers members of the FIM. Informed consent was provided by the pts. Data collected included characteristics of the disease, treatment, responses to ruxolitinib and ESA. They are reported according to the IWG-MRT/ELN 2013 criteria.ResultsThis analysis was performed in July 2016, on the 45 first consecutive pts in 11 centers. Median age at diagnosis was 73 (range 42- 89), 30 (67%) were men. Twenty-five pts (56%) had primary MF, 11 (24%) PET-MF and 9 (20%) PPV-MF, overall diagnosed between 2004 and 2016. IPSS risk categories were low/int-1 and int-2/high in 16 (36%) and 28 (64%) pts, respectively. Twenty-nine (64%) were JAK2V617F positive, 5 harbored MPL mutation and 8 had CALR mutations.Median time between MF diagnosis and ruxolitinib was 21 (0-109) months and median follow-up from ruxolitinib starting was 13 (2 - 53) months. At time of ruxolitinib initiation 32 (71%) pts were transfusion independent and 13(29%) had transfusion need. Ten additional pts became transfusion dependent after ruxolitinib initiation. Other causes of anemia were renal insufficiency n=7, surgery n=1, 1 cytoreductive therapy with hydroxyurea.Type of ESA were darbepoetin alfa, [n=26]; epoetin alfa, [n=3], epoetin beta [n=8], epoetin zeta [n=4], epoeitin theta [n=4], with a median duration of exposure to ESA of 15 months [1-92mo]. ESA was introduced either before ruxolitinib (n= 17), simultaneously (n= 4) or afterward (n= 24) after a median of 2 months [1-26mo].Response rate to ruxolitinib were in accordance with previous reports: For splenomegaly, 33 (73%) of pts achieved at least a partial response, 8 (17%) were stable and 4 (9%) were progressive. Thirty pts (67%) had at least partial response on constitutional symptoms.Response assessment of anemia according to IWG-MRT/ELN 2013 criteria: 7 pts (16%) achieved a RBC transfusion independency, 13 (29%) pts had an increase in hemoglobin level of Hb >2g/dl (2 pts achieved both criteria), which results in 40% of objective responses. The median time to best response on anemia after ESA initiation was 3 [1-84] months.For safety, a pulmonary embolism occurred in one patient possibly related to ESA, no other adverse event occurred, in particular no spleen enlargement was described.At time of analysis, 36/45 pts were still alive: 1 underwent allogeneic bone marrow transplant, 34 were still treated with ruxolitinib whereas 28 patients were still undergoing ESA therapy.ConclusionsThis retrospective analysis is the largest cohort describing the use of concomitant ESA with ruxolitinib therapy in "real life". We report 40 % of objective responses, consistent with ESA response rates without ruxolitinib for MF related anemia. Tolerance seemed acceptable without hampering efficiency of ruxolitinib. Our results suggest that ESA should be considered as a possible therapeutic for anemia in myelofibrosis patients treated with ruxolitinib

The neuropeptide substance P regulates aldosterone secretion in human adrenals

International audienceAldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes