Recruitment of a lineage-specific virulence regulatory pathway promotes intracellular infection by a plant pathogen experimentally evolved into a legume symbiont

Ajuts: We are grateful to Lidwine Trouilh for helping in NimbleGen microarray hybridizations and Loic Escoriza for mutant construction. J.P.C. and C.C. were supported by the Initiative d'Excellence IDEX UNITI Actions Thématiques Stratégiques program (RHIZOWHEAT 2014) and by the French National Research Agency (ANR-12-ADAP-0014-01). This work was supported by funds from the French National Institute for Agricultural Research (Plant Health and the Environment Division), the French National Research Agency (ANR-12-ADAP-0014-01) and the French Laboratory of Excellence project TULIP (ANR-10-LABX-41). The complete collections of events generated for all the clones from this study are available on the Microscope platform (https://www.genoscope.cns.fr/agc/microscope/expdata/NGSProjectEvo.php, SYMPA tag).Ecological transitions between different lifestyles, such as pathogenicity, mutualism and saprophytism, have been very frequent in the course of microbial evolution, and often driven by horizontal gene transfer. Yet, how genomes achieve the ecological transition initiated by the transfer of complex biological traits remains poorly known. Here we used experimental evolution, genomics, transcriptomics and high-resolution phenotyping to analyze the evolution of the plant pathogen Ralstonia solanacearum into legume symbionts, following the transfer of a natural plasmid encoding the essential mutualistic genes. We show that a regulatory pathway of the recipient R. solanacearum genome involved in extracellular infection of natural hosts was reused to improve intracellular symbiosis with the Mimosa pudica legume. Optimization of intracellular infection capacity was gained through mutations affecting two components of a new regulatory pathway, the transcriptional regulator efpR and a region upstream from the RSc0965-0967 genes of unknown functions. Adaptive mutations caused the downregulation of efpR and the over-expression of a downstream regulatory module, the three unknown genes RSc3146-3148, two of which encoding proteins likely associated to the membrane. This over-expression led to important metabolic and transcriptomic changes and a drastic qualitative and quantitative improvement of nodule intracellular infection. In addition, these adaptive mutations decreased the virulence of the original pathogen. The complete efpR/RSc3146-3148 pathway could only be identified in the genomes of the pathogenic R. solanacearum species complex. Our findings illustrate how the rewiring of a genetic network regulating virulence allows a radically different type of symbiotic interaction and contributes to ecological transitions and trade-offs

A 60-million-year Cenozoic history of western Amazonian ecosystems in Contamana, eastern Peru

Weprovide a synopsis of ~60million years of life history in Neotropical lowlands, based on a comprehensive survey of the Cenozoic deposits along the Quebrada Cachiyacu near Contamana in PeruvianAmazonia. The 34 fossilbearing localities identified have yielded a diversity of fossil remains, including vertebrates,mollusks, arthropods, plant fossils, and microorganisms, ranging from the early Paleocene to the lateMiocene–?Pliocene (N20 successive levels). This Cenozoic series includes the base of the Huchpayacu Formation (Fm.; early Paleocene; lacustrine/ fluvial environments; charophyte-dominated assemblage), the Pozo Fm. (middle + ?late Eocene; marine then freshwater environments; most diversified biomes), and complete sections for the Chambira Fm. (late Oligocene–late early Miocene; freshwater environments; vertebrate-dominated faunas), the Pebas Fm. (late early to early late Miocene; freshwater environments with an increasing marine influence; excellent fossil record), and Ipururo Fm. (late Miocene–?Pliocene; fully fluvial environments; virtually no fossils preserved). At least 485 fossil species are recognized in the Contamana area (~250 ‘plants’, ~212 animals, and 23 foraminifera). Based on taxonomic lists from each stratigraphic interval, high-level taxonomic diversity remained fairly constant throughout themiddle Eocene–Miocene interval (8-12 classes), ordinal diversity fluctuated to a greater degree, and family/species diversity generally declined, with a drastic drop in the early Miocene. The Paleocene–?Pliocene fossil assemblages from Contamana attest at least to four biogeographic histories inherited from (i) Mesozoic Gondwanan times, (ii) the Panamerican realm prior to (iii) the time of South America’s Cenozoic “splendid isolation”, and (iv) Neotropical ecosystems in the Americas. No direct evidence of any North American terrestrial immigrant has yet been recognized in the Miocene record at Contamana.Facultad de Ciencias Naturales y Muse

Monoclonal antibodies for prophylactic and therapeutic use against viral infections

Neutralizing antibodies play an essential part in antiviral immunity and are instrumental in preventing or modulating viral diseases. Polyclonal antibody preparations are increasingly being replaced by highly potent monoclonal antibodies (mAbs). Cocktails of mAbs and bispecific constructs can be used to simultaneously target multiple viral epitopes and to overcome issues of neutralization escape. Advances in antibody engineering have led to a large array of novel mAb formats, while deeper insight into the biology of several viruses and increasing knowledge of their neutralizing epitopes has extended the list of potential targets. In addition, progress in developing inexpensive production platforms will make antiviral mAbs more widely available and affordable

Non-heat related impacts of climate change on working populations

Environmental and social changes associated with climate change are likely to have impacts on the well-being, health, and productivity of many working populations across the globe. The ramifications of climate change for working populations are not restricted to increases in heat exposure. Other significant risks to worker health (including physical hazards from extreme weather events, infectious diseases, under-nutrition, and mental stresses) may be amplified by future climate change, and these may have substantial impacts at all scales of economic activity. Some of these risks are difficult to quantify, but pose a substantial threat to the viability and sustainability of some working populations. These impacts may occur in both developed and developing countries, although the latter category is likely to bear the heaviest burden

Transient Alteration of Cellular Redox Buffering before Irradiation Triggers Apoptosis in Head and Neck Carcinoma Stem and Non-Stem Cells

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy owing to intrinsic radioresistance and lack of induction of apoptosis. The major focus of this work was to design a transient glutathione depleting strategy during the course of irradiation of HNSCC in order to overcome their radioresistance associated with redox adaptation. Methodology/Principal Findings: Treatment of SQ20B cells with dimethylfumarate (DMF), a GSH-depleting agent, and L-Buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis 4 h before a 10 Gy irradiation led to the lowering of the endogenous GSH content to less than 10 % of that in control cells and to the triggering of radiation-induced apoptotic cell death. The sequence of biochemical events after GSH depletion and irradiation included ASK-1 followed by JNK activation which resulted in the triggering of the intrinsic apoptotic pathway through Bax translocation to mitochondria. Conclusions: This transient GSH depletion also triggered radiation-induced cell death in SQ20B stem cells, a key event to overcome locoregional recurrence of HNSCC. Finally, our in vivo data highlight the relevance for further clinical trials o

The formation of human populations in South and Central Asia

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization’s decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages

BMC Psychol

Background Preschoolers regularly display disruptive behaviors in child care settings because they have not yet developed the social skills necessary to interact prosocially with others. Disruptive behaviors interfere with daily routines and can lead to conflict with peers and educators. We investigated the impact of a social skills training program led by childcare educators on children’s social behaviors and tested whether the impact varied according to the child’s sex and family socio-economic status. Methods Nineteen public Child Care Centers (CCC, n = 361 children) located in low socio-economic neighborhoods of Montreal, Canada, were randomized into one of two conditions: 1) intervention (n = 10 CCC; 185 children) or 2) wait list control (n = 9 CCC; 176 children). Educators rated children’s behaviors (i.e., disruptive and prosocial behaviors) before and after the intervention. Hierarchical linear mixed models were used to account for the nested structure of the data. Results At pre-intervention, no differences in disruptive and prosocial behaviors were observed between the experimental conditions. At post-intervention, we found a significant sex by intervention interaction (β intervention by sex = − 1.19, p = 0.04) indicating that girls in the intervention condition exhibited lower levels of disruptive behaviors compared to girls in the control condition (f2 effect size = − 0.15). There was no effect of the intervention for boys. Conclusions Girls may benefit more than boys from social skills training offered in the child care context. Studies with larger sample sizes and greater intervention intensity are needed to confirm the results

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

L'avenir du travail policier

Cet ouvrage tente de cerner les tendances sociales, technologiques ou économiques associées à l'avènement d'Internet et à la mondialisation des échanges qui transforment le travail policier. Il s'agit d'un portrait précis et exhaustif de cette mouvance qui influence et façonne irrémédiablement les pratiques professionnelles des institutions chargées de faire appliquer la loi et de garantir la sécurité des citoyens.À la fois bilan de ce qui est à retenir ou à rejeter et photographie des meilleures avenues pour penser l'avenir, on y aborde cinq thèmes, tous en relation avec la réalité du Canada : l'extrémisme violent, la cybercriminalité, les critères de mesure de l'efficacité du travail policier, les médias sociaux et enfin l'usage des algorithmes. Ce collectif réunit cinq chercheurs de grande réputation qui analysent et documentent la nature de cette évolution sociétale sur les organisations policières dans un contexte technologique en perpétuel mouvement.Il s'adresse particulièrement aux chercheurs et aux étudiants en criminologie et en science politique, mais aussi aux politiques, aux gestionnaires policiers et aux journalistes qui couvrent les affaires criminelles ; enfin à tous ceux qui s'intéressent au fonctionnement de la police