Erythropoietin Down-Regulates Stem Cell Factor Receptor (Kit) Expression in the Leukemic Proerythroblast: Role of Lyn Kinase

Overexpression of the transcription factor Spi-1/PU.1 by transgenesis in mice induces a maturation arrest at the proerythroblastic stage of differentiation. We have previously isolated a panel of spi-1 transgenic erythroleukemic cell lines that proliferated in the presence of either erythropoietin (Epo) or stem cell factor (SCF). Using these cell lines, we observed that EpoR stimulation by Epo down-regulated expression of the SCF receptor Kit and induced expression of the Src kinase Lyn. Furthermore, enforced expression of Lyn in the cell lines increased cell proliferation in response to Epo, but reduced cell growth in response to SCF in accordance with Lyn ability to down-regulate Kit expression. Together, the data suggest that Epo-R/Lyn signaling pathway is essential for extinction of SCF signaling leading the proerythroblast to strict Epo dependency. These results highlight a new role for Lyn as an effector of EpoR in controlling Kit expression. They suggest that Lyn may play a central role in during erythroid differentiation at the switch between proliferation and maturation

Insight into the Distribution of High-pressure Shock Metamorphism in Rubble-pile Asteroids

Funding Information: This work was supported by the Academy of Finland, project Nos. 293975 and 335595, the European Regional Development Fund, the Mobilitas Pluss programme (grant No. MOBJD639), and the NASA Solar System Exploration Research Virtual Institute Center for Lunar and Asteroid Surface Science, and it was conducted within institutional support RVO 67985831 of the Institute of Geology of the Czech Academy of Sciences. R.L. appreciates funding from the European Union’s Horizon 2020 research and innovation program, NEO-MAPP, grant agreement No. 870377. Publisher Copyright: © 2022. The Author(s). Published by the American Astronomical Society.Shock metamorphism in ordinary chondrites allows for reconstructing impact events between asteroids in the main asteroid belt. Shock-darkening of ordinary chondrites occurs at the onset of complete shock melting of the rock (>70 GPa) or injection of sulfide and metal melt into the cracks within solid silicates (∼50 GPa). Darkening of ordinary chondrites masks diagnostic silicate features observed in the reflectance spectrum of S-complex asteroids so they appear similar to C/X-complex asteroids. In this work, we investigate the shock pressure and associated metamorphism pattern in rubble-pile asteroids at impact velocities of 4–10 km s−1. We use the iSALE shock physics code and implement two-dimensional models with simplified properties in order to quantify the influence of the following parameters on shock-darkening efficiency: impact velocity, porosity within the asteroid, impactor size, and ejection efficiency. We observe that, in rubble-pile asteroids, the velocity and size of the impactor are the constraining parameters in recording high-grade shock metamorphism. Yet, the recorded fraction of higher shock stages remains low (<0.2). Varying the porosity of the boulders from 10% to 30% does not significantly affect the distribution of pressure and fraction of shock-darkened material. The pressure distribution in rubble-pile asteroids is very similar to that of monolithic asteroids with the same porosity. Thus, producing significant volumes of high-degree shocked ordinary chondrites requires strong collision events (impact velocities above 8 km s−1 and/or large sizes of impactors). A large amount of asteroid material escapes during an impact event (up to 90%); however, only a small portion of the escaping material is shock-darkened (6%).Peer reviewe

The dystroglycan: Nestled in an adhesome during embryonic development

AbstractInvertebrate and vertebrate development relies on complex processes that require many coordinated cell functions including cell adhesion, migration, proliferation and polarization. These processes depend on tissues and are spatio-temporally regulated by specific interactions between cells and between cells and the extracellular matrices. The dystroglycan, a transmembrane receptor that binds multiple extracellular matrix proteins, is expressed from oogenesis to organogenesis. There are increasing data suggesting that the axis, consisting of extracellular component–dystroglycan–cytoplasmic proteins, controls both the adhesion of cells to matrices as well as the transduction of signals coming from or directed to matrices. In this article, we review current advances leading to consider that the dystroglycan is a key protein nestled in an adhesome involved in mechanisms of cell adhesion during embryonic development

Experimental infection of Pacific oyster Crassostrea gigas spat by ostreid herpesvirus 1: demonstration of oyster spat susceptibility

In 2008 and 2009, acute mortalities occurred in France among Pacific cupped oyster, Crassostrea gigas, spat. Different hypothesis including the implication of environmental factors, toxic algae and/or pathogens have been explored. Diagnostic tests indicated that OsHV-1 including a particular genotype, termed OsHV-1 μVar, was detected in most of samples and especially in moribund oysters with the highlighting of virus particles looking like herpes viruses by TEM examination. In this study, an experimental protocol to reproduce OsHV-1 infection in laboratory conditions was developed. This protocol was based on the intramuscular injection of filtered (0.22 μm) tissue homogenates prepared from naturally OsHV-1 infected spat collected on French coasts during mortality outbreaks in 2008. Results of the experimental trials showed that mortalities were induced after injection. Moreover, filtered tissue homogenates induced mortalities whereas the same tissue homogenates exposed to an ultraviolet (UV) treatment did not induce any mortality suggesting that oyster spat mortalities require the presence of a UV sensitive agent. Furthermore, analysis of injected oyster spat revealed the detection of high amounts of OsHV-1 DNA by real-time quantitative PCR. Finally, TEM analysis demonstrated the presence of herpes virus particles. The developed protocol allowed to maintain sources of infective virus which can be useful for the development of further studies concerning the transmission and the development of OsHV-1 infection

La qualité de vie au travail des éducatrices de la petite enfance

Cet article traite de la qualité de vie au travail des éducatrices de la petite enfance. Il présente les résultats d’une enquête réalisée au Québec auprès de 519 éducatrices travaillant en centre de la petite enfance. Au total, cinq sources de stress (Boyle, Borg, Falzon, &amp; Baglioni, 1995), cinq sources de bien-être psychologique (Dagenais- Desmarais, 2010) et une mesure d’autonomie (Gillet, Rosnet, &amp; Vallerand, 2008) au travail sont considérées. Dans l’ensemble, les résultats révèlent un niveau de stress plutôt bas et des niveaux de bien-être et d’autonomie plutôt élevés. Analysés par tranche d’expérience, les résultats montrent que les cinq premières années au travail sont généralement suivies d’une augmentation du stress et d’une diminution du bien-être psychologique. Ils montrent aussi que l’autonomie est fortement associée au bien-être psychologique. Sur le plan pratique, ces résultats invitent les gestionnaires et les formateurs d’éducatrices de la petite enfance à porter une attention particulière aux premières années de vie professionnelle ainsi qu’à la préparation et à la mise en place de conditions favorables à l’exercice de l’autonomie au travail.

Communication Plan

This document outlines the main communication objectives, messages, audiences, and tools of the EuroSea projec

Estimating the Timing of Mother-to-Child Transmission of the Human Immunodeficiency Virus Type 1 Using a Viral Molecular Evolution Model

Background: Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT. Materials and Methods Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277–1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays. Results: Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery. Conclusions: The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events

Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand

Background: Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 $log_{10}$ IU/mL and 4.47 $log_{10}$ copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions: All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC

Le Forum, Vol. 44 #2

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