Mitapivat, a pyruvate kinase activator, improves transfusion burden and reduces iron overload in M-thalassemic mice

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Resveratrol Induces Erythroid Maturation by Activating FOXO3 and Improves in Vivo Erythropoiesis in Normal and Beta -Thalassemic Mice

Resveratrol is a polyphenolic stilbene with anti-oxidant, anti-inflammatory and anti-tumoral bioactivities . High concentrations of resveratrol (50 \u3bcM) have been reported to induce HbF synthesis in an in vitro model of normal and beta-thalassemic erythropoiesis (Fibach E. Int J Mol Med 2012; Rodrigue CM. BJH 2001) and to improve erythropoiesis in a mouse model for Fanconi Anemia (Zhang Q. Blood 2010). Beta thalassemia (b-thal) is characterized by ineffective erythropoiesis and increased cellular oxidative stress. We studied the effects of resveratrol (5 \ub5M) on erythropoiesis in vitro from peripheral CD34+ cells of healthy and b-thal subjects. Erythroid maturation was evaluated at 7, 9, 11 and 14 days of culture by cytofluorimetric analysis using the CD71-GPA-CD36 strategy that allows to separate CFU-E, Pro-E, Int-E and Late-Erythroblasts (Merryweather-Clarke AT. Blood 2011). Resveratrol reduced cell growth in both cell types, with a reduction of CFU-E, increased Int-E at day 7 and 9, and increased Int-E and Late-E at 11 and 14 days. The early maturation of erythroid progenitors was confirmed by morphological analysis of the cells. We sorted CFU-E cells (at 7 days) from resveratrol treated and untreated cells and analyzed the cell cycle, cyclinD1 and p21 expression. In both cell types resveratrol induced increased frequency of S-G2/M cells compared to untreated cells with increased p21 levels, suggesting decreased cycling of CFU-E with increased maturation of erythroblasts. No changes of gamma chain mRNA levels were present in cells treated with resveratrol (5 \ub5M). Since FOXO3 is a key regulator of erythroid redox required for normal erythroid maturation (Marinkovic D. JCI 2007), FOXO3 expression and activity was assessed in sorted CFU (7day) and Int-E (11 day) with and without resveratrol. FOXO3a mRNA levels were increased in resveratrol treated cells in both sorted cell populations. We used nuclear localization as a surrogate assay for FOXO3a activity and found resveratrol increased the overall expression of FOXO3 protein in the nucleus without impacting significantly the nuclear/cytoplasmic ratio. Interestingly, resveratrol did not appear to modify FOXO1 expression or subcellular localization. These results suggest that resveratrol enhances specifically expression of FOXO3 in human erythroblasts. Dietary resveratrol supplementation (2.4 mg/Kg) was studied in wild-type and Hbb3th+/- mice (2 months of age) for 6 months. In resveratrol Hbb3th+/- treated mice increased Hb levels (8.3\ub10.6 vs 10.3\ub10.5 g/dL, n=12; P<0.05) and decreased reticulocyte count (33.9\ub10.8 vs 23.7\ub1 8.2 %, n=12; P<0.05) were observed. Significant increased MCV (34.6\ub10.6 vs 41.6\ub1 5.4 fL, n=12; P<0.05) and MCH ( 9.7\ub1 0.6 vs 12.8 \ub1 2.1 pg, n=12; P<0.05) were also noted. Flow cytometric evidence of decreased ineffective erythropoiesis and reduced spleen/ body weight ratio were also observed. These data indicate that resveratrol affects erythroid maturation both in vitro and in vivo, and that these effects have possible therapeutic relevance for the treatment of thalassemias

Neural Network Based Approach to Recognition of Meteor Tracks in the Mini-EUSO Telescope Data

Mini-EUSO is a wide-angle fluorescence telescope that registers ultraviolet (UV) radiation in the nocturnal atmosphere of Earth from the International Space Station. Meteors are among multiple phenomena that manifest themselves not only in the visible range but also in the UV. We present two simple artificial neural networks that allow for recognizing meteor signals in the Mini-EUSO data with high accuracy in terms of a binary classification problem. We expect that similar architectures can be effectively used for signal recognition in other fluorescence telescopes, regardless of the nature of the signal. Due to their simplicity, the networks can be implemented in onboard electronics of future orbital or balloon experiments.Comment: 15 page

Genetic variance in fitness indicates rapid contemporary adaptive evolution in wild animals

Funding: Hoge Veluwe great tits: the NIOO-KNAW, ERC, and numerous funding agencies; Wytham great tits: Biotechnology and Biological Sciences Research Council, ERC, and the UK Natural Environment Research Council (NERC).The rate of adaptive evolution, the contribution of selection to genetic changes that increase mean fitness, is determined by the additive genetic variance in individual relative fitness. To date, there are few robust estimates of this parameter for natural populations, and it is therefore unclear whether adaptive evolution can play a meaningful role in short-term population dynamics. We developed and applied quantitative genetic methods to long-term datasets from 19 wild bird and mammal populations and found that, while estimates vary between populations, additive genetic variance in relative fitness is often substantial and, on average, twice that of previous estimates. We show that these rates of contemporary adaptive evolution can affect population dynamics and hence that natural selection has the potential to partly mitigate effects of current environmental change.PostprintPeer reviewe

Euclid Near Infrared Spectrometer and Photometer instrument concept and first test results obtained for different breadboards models at the end of phase C

The Euclid mission objective is to understand why the expansion of the Universe is accelerating through by mapping the geometry of the dark Universe by investigating the distance-redshift relationship and tracing the evolution of cosmic structures. The Euclid project is part of ESA's Cosmic Vision program with its launch planned for 2020 (ref [1]). The NISP (Near Infrared Spectrometer and Photometer) is one of the two Euclid instruments and is operating in the near-IR spectral region (900- 2000nm) as a photometer and spectrometer. The instrument is composed of: - a cold (135K) optomechanical subsystem consisting of a Silicon carbide structure, an optical assembly (corrector and camera lens), a filter wheel mechanism, a grism wheel mechanism, a calibration unit and a thermal control system - a detection subsystem based on a mosaic of 16 HAWAII2RG cooled to 95K with their front-end readout electronic cooled to 140K, integrated on a mechanical focal plane structure made with molybdenum and aluminum. The detection subsystem is mounted on the optomechanical subsystem structure - a warm electronic subsystem (280K) composed of a data processing / detector control unit and of an instrument control unit that interfaces with the spacecraft via a 1553 bus for command and control and via Spacewire links for science data This presentation describes the architecture of the instrument at the end of the phase C (Detailed Design Review), the expected performance, the technological key challenges and preliminary test results obtained for different NISP subsystem breadboards and for the NISP Structural and Thermal model (STM)

Caractérisation de la dispersion à fine échelle chez la mésange bleue (Cyanistes caeruleus) en Corse

La dispersion est l’un des principaux mécanismes façonnant l’évolution de la biodiversité et l’un des moteurs fondamentaux de la dynamique des populations. Il s’agit donc un thème majeur d’étude en écologie, en évolution et en biologie de la conservation. La dispersion peut concerner deux moments différents de la vie d’un organisme : la dispersion natale lorsque les juvéniles quittent leur lieu de naissance pour trouver leur lieu de première reproduction, et la dispersion de reproduction entre deux évènements de reproduction successifs. Malgré leur importance, les phénomènes de dispersion sont difficiles à étudier sur de longues distances. Nous avons étudié la dispersion natale et de reproduction chez un passereau européen commun, la mésange bleue, grâce à un suivi à long terme existant sur trois stations équipées de nichoirs, en Corse. Les 2491 données d’évènements de dispersion de reproduction montrent que les mâles et femelles de mésange bleue s’installent respectivement à 32 mètres (±103m) et 47 mètres (±115) de leur lieu de dernière reproduction. Un protocole inédit de captures en dehors des stations d’études habituelles a été mis en œuvre deux printemps consécutifs. Ce nouveau protocole spécifique à l’étude de la dispersion a permis de réduire les biais d’estimation des distances de dispersion natale et du sex-ratio des individus recrutés, biais inhérents à la forme et à la taille des stations d’étude habituelles. Ce protocole incluant des captures hors-station a révélé que les distances de dispersion natale des mésanges bleues en Corse sont en réalité plus élevées que celles calculées précédemment uniquement au sein des stations. Ce protocole spécifique à l’étude de la dispersion confirme et augmente les différences de distances de dispersion entre mâles et femelles. Enfin, nous avons exploré les déterminants de la dispersion natale de 1236 individus. Ainsi, la distance de dispersion des poussins mâles est corrélée à leur date d’éclosion (les mâles des nichées tardives dispersent plus loin), à leur docilité (les mâles plus agités dispersent plus loin) et à leur masse (les mâles plus légers dispersent plus loin). Dans deux stations d’étude, une forte densité de reproducteurs est associée à des distances de dispersion plus faibles pour les poussins. De plus, les individus d’une même famille partagent des comportements de dispersion similaires. Enfin, les mésanges bleues issues des populations en chêne vert et en chêne blanc semblent disperser sur les habitats similaires plutôt que sur d’autres essences. Ces résultats montrent l’importance de s’affranchir des limites du site d’étude ou du moins d’élargir les périmètres d’étude au-delà des zones de nichoirs pour caractériser la dispersion natale. Les résultats obtenus sur les poussins mâles mettent en lumière l’importance des facteurs impliqués dans la première phase de la dispersion : l’émigration et invite à étudier cette étape clef dans la vie d’une mésange

Plant consumer innovation in skuas

International audienceWe report observations of alien dandelion (Taraxacum officinale group) consumption in an opportunistic predatory seabird, the brown skua (Stercorarius antarcticus lonnbergi), from a natural population on île Verte within the Kerguelen archipelago. Observations on a nearby island suggest that this behaviour is not specific to our study area, paving the way to future studies investigating whether this consumer innovation prevails in skua populations and results in dietary benefits

Identifying drivers of spatio-temporalvariation in survival in four blue tit populations

International audienceIn a context of rapid climate change, the influence of large-scale and local climate on population demography is increasingly scrutinized, yet studies are usually focused on one population. Demographic parameters, including survival, can vary significantly across populations of a given species, depending on global or local climatic fluctuations but also on many other population-specific parameters such as breeding density, habitat naturalness, predation or parasitism. Such ecological differences between populations could lead to different paces-of-life (POL), whereby populations where individuals display higher reproductive investment and bolder behaviours would have lower survival probabilities. We use here long-term (19 to 38 years) monitoring datasets from four Mediterranean populations of blue tits (Cyanistes caeruleus) to investigate the effects of sex, age class, large-scale and local climate temporal variation and population breeding density, on adult survival, using Capture-Mark-Recapture modelling. Environment heterogeneity in these four populations (two in evergreen and two in deciduous forests) has been linked to strong multi-trait phenotypic variation, suggesting blue tits in deciduous forests display faster POL compared to their conspecifics in evergreen habitats. The present results show heterogeneity in average survival probabilities across the four populations, with, as predicted, lower survival in the 'fast' blue tits occupying deciduous habitats. Interestingly, the year-to-year variation in survival probabilities was synchronous among populations. This suggests that regional environmental conditions could drive survival fluctuations across populations. However, breeding densities were not correlated across populations, and we found no evidence that adult survival is correlated with either large-scale or local, climate temporal variation in these four blue tit populations. Finally, two of the focal populations displayed a linear temporal decrease in adult survival over the study period, calling for further investigation to explain this decline. Overall, this multi-site study shows that blue tit parental survival from one spring to the next can vary substantially across years, in a synchronous way across populations, yet the climate indices we used are not correlated with the temporal variation. This calls for further investigations in other potential drivers such as resource (in particular insect) abundance, predation or parasitism