Soluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.

peer reviewedEpithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread

Former les professionnels de l’information et de la documentation aux données de la recherche en 45 minutes

Ce document est un outil clef en main pour réaliser, en interne, une formation basique aux données de la recherche en 45 minutes. Elle a été pensée pour des personnels des bibliothèques ou centre de documentation qui sont novices dans le domaine et ont besoin d’être sensibilisés. En effet, dans le monde universitaire, les données sont un élément à connaître, au moins de nom, par tout agent en situation d’accueil dans une bibliothèque. Les parties « l’essentiel » permettent de former des agents aux bases en 45 minutes. La formation peut être étendue à 1h30 en utilisant également les parties « pour développer ». Il est également possible de faire la formation en 45 minutes puis de distribuer la trame pour que les participants lisent les parties « pour développer » ultérieurement

S’autoformer aux données de la recherche : guide à destination des professionnels de l\u27information et de la documentation

Ce guide d\u27autoformation est destiné aux professionnels de l\u27information et de la documentation qui souhaitent faire progresser leurs compétences dans le domaine des données de la recherche, qu\u27ils soient débutants ou confirmés

Etiology and factors associated with pneumonia in children under 5 years of age in Mali: A prospective case-control study

Background: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. Methods: A prospective hospital-based case-control study

FDR4ATMOS (Task A): Improving SCIAMACHY Level 1 and add calibrated lunar data

The project FDR4ATMOS (Fundamental Data Records in the domain of satellite Atmospheric Composition) has been initiated by the European Space Agency (ESA). Task A of the project covers the improvement of the SCIAMACHY Level 1b degradation correction, with the aim to remove ozone trends from the SCIAMACHY Level 2 data set that were introduced during the development of baseline version 9 (both data sets not released). We will also, for the first time, add calibrated lunar data to Level 1, covering the whole spectral range of SCIAMACHY and the full mission time. The SCIAMACHY processing chain for better Ozone total column data: After the full re-processing of the SCIAMACHY mission with the updated processor versions, the validation showed that the total Ozone column drifted downward by nearly 2% over the mission lifetime. This drift is likely caused by changes in the degradation correction in the Level 1 processor, that led to subtle changes in the spectral structures. These are misinterpreted as an atmospheric signature. We updated the Level 0-1 processor accordingly and a full mission re-processing was done. As a major improvement we additionally incorporated calibrated lunar data in the SCIAMACHY Level 1b product. In the new Level 1b product we will provide the individual scans of the moon as well as disk integrated and calibrated lunar irradiance and reflectance. The instrument performed regular lunar observations building up a unique 10 year data set of lunar spectra from the UV to the SWIR with moderately high spectral resolution. SCIAMACHY scanned the full lunar disk and over the ten year mission time made 1123 observations of the moon. Most satellites can only observe the moon under very specific geometries due to instrument-viewing and orbit restrictions. SCIAMACHY, however, with a two mirror pointing system was much less constrained and was able to observe the moon under an extreme large variation of geometries (especially during dedicated lunar observation campaigns), allowing it thus potentially to tie different satellites and geometry observations together. During the individual lunar observations, SCIAMACHY only saw a small slice of the Moon and scanned over the moon in order to obtain data for the full disk. We combined the individual calibrated scans, correcting for scan speed and the fact the Moon does not fill the entire slit length. The calculation of distance-normalized lunar reflectances did not require an external solar spectrum, but used solar measurements of SCIAMACHY itself. This version of Level 1 will also be the first one that replaces the ENVISAT byte stream format with the netCDF format that is aligned with the product format of other atmospheric sensors like the Sentinels The paper will present the improvements of the Level 1 product, the results of the quality control and validation

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Applied population genomics : detection of signatures of selection in experimental populations

La génomique des populations rend possible la mise en évidence de traces de sélection dans le génome. Les travaux effectués considèrent en général une échelle de temps longue (~ 10³ générations). En comparaison, peu d’intérêt a été porté aux études expérimentales de court terme (~ 10 générations). De telles expériences sont pourtant susceptibles de nous renseigner sur la base génétique de caractères complexes. Nous proposons une méthode de vraisemblance basée sur un modèle de Wright-Fisher pour détecter la sélection à partir d’échantillons génétiques temporels acquis sur une période de dix générations. Nous montrons par simulation que notre méthode permet de différencier les signaux dus à la combinaison de la sélection et de la dérive génétique de ceux dus à la dérive seule. Nous montrons également par simulation qu’il est possible d’estimer le coefficient de sélection appliqué à un locus testé. De plus, nous illustrons l’intérêt de notre méthode pour la détection de marqueurs candidats à la sélection au travers de deux études génomiques sur données réelles, chez le diable de Tasmanie (Sarcophilus harrisii) et chez la truite arc-en-ciel (Oncorhynchus mykiss). Ces applications mettent en évidence des régions génomiques candidates pour des phénotypes complexes dans des contextes différents. Dans l’ensemble, nos résultats montrent qu’il est possible de détecter des gènes sujets à une sélection directionnelle intense à partir d’échantillons génétiques temporels, même si la sélection est de courte durée et si les populations examinées ont un faible effectif.Population genomics makes it possible to detect traces of selection in the genome. Studies in this field have mainly focused on long time scale (~ 10³ generations). In comparison, short-term experimental studies (~ 10 generations) have attracted much less interest. Such experiments are, however, likely to inform us about the genetic basis of complex characters. We propose a likelihood method based on a Wright-Fisher model to detect selection from genetic temporal samples collected over ten generations. We show through simulation that our method can disentangle signals due to the combination of genetic drift and selection to those due to drift alone. We also show through simulation that it is possible to estimate the selection coefficient applied to a tested locus. In addition, we illustrate the interest of our method for the detection of candidate markers for selection through two genome scans performed on real data, in the Tasmanian devil (Sarcophilus harrisii) and in the rainbow trout (Oncorhynchus mykiss). These practical applications highlight candidate genomic regions for complex phenotypes in different contexts. Collectively, our results show the possibility of detecting genes submitted to strong directional selection from genetic time-series, even if selection is applied on a short time period and if the examined populations are small