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Abstract The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap methylation via the RNA dependent RNA polymerase, capping, and Methyltransferase domains on L. Several nucleoside and non-nucleoside inhibitors have been reported to inhibit this polymerase complex, but the structural details of the exact inhibitor-polymerase interactions have been lacking. Here, we report a non-nucleoside inhibitor JNJ-8003 with sub-nanomolar inhibition potency in both antiviral and polymerase assays. Our 2.9 Å resolution cryo-EM structure revealed that JNJ-8003 binds to an induced-fit pocket on the capping domain, with multiple interactions consistent with its tight binding and resistance mutation profile. The minigenome and gel-based de novo RNA synthesis and primer extension assays demonstrated that JNJ-8003 inhibited nucleotide polymerization at the early stages of RNA transcription and replication. Our results support that JNJ-8003 binding modulates a functional interplay between the capping and RdRp domains, and this molecular insight could accelerate the design of broad-spectrum antiviral drugs.

Review of: Frederick A. De Armas. Cervantes’ Architectures: The Dangers Outside, Toronto, Toronto University Press, 2022, 384 pp.

Très ancienne culture, la Chine a très tôt développé un intérêt fort pour l’élaboration et la consommation du thé, comme l’atteste le temple de l’Institut Royal du Thé de la Dynastie Tang à Changxing. Yu Lu (733-804) peut être considéré comme le père fondateur de la culture du thé de terroir : le meilleur thé pour l’Empereur, issu des meilleurs lieux pour le produire, avec les variétés les plus appropriées. L’une d’entre elles, unique en un terroir particulier, se manifeste par un port de feuille original et reconnaissable avec évidence. Il existe donc des « Hauts-lieux » pour la culture du thé comme il existe des « Hauts-lieux » pour la culture de la vigne. Cette culture du thé retrouve toute sa vigueur aujourd’hui, mais depuis quelques années on assiste également à un fort intérêt pour le vin, en particulier pour les grands vins de terroir dont la Bourgogne est le modèle. Nous explorons le sens de cet intérêt grandissant chez ces amateurs de vin et de thé.

Abstract Background Elderly people in nursing homes are particularly vulnerable to COVID-19 due to their age, the presence of comorbidities, and community living. On March 14, 2020, at the beginning of the first epidemic wave of COVID-19 in France, a cluster was reported in a nursing home in the Nouvelle-Aquitaine region. We monitored the outbreak as well as the infection prevention and control (IPC) measures implemented. Methods A confirmed case was defined as laboratory-confirmed COVID-19 in a resident or staff member present in the nursing home between March 7 and May 1, 2020; and a probable case as a person presenting an acute respiratory illness after contact with a confirmed case. Symptomatic inpatient residents and symptomatic staff members were systematically tested for SARS-CoV-2. In addition, two screening sessions were held on site. Results We identified 109 cases (98 confirmed, 11 probable). The attack rate was 66% among residents and 45% among staff. Half of all cases were identified during the screening sessions. One-quarter of cases had minor symptoms or were asymptomatic. The case fatality rate among residents was 29%. IPC measures were rapidly implemented such as the quarantine of residents, the reinforcement of staff personal protective equipment, and home quarantine of staff testing positive, which were supplemented in April by systematic controls at the entrance of the nursing home and the creation of additional staff break rooms. Conclusions This outbreak confirmed the considerable health impact of SARS-CoV-2 transmission in a nursing home. In addition to the implementation of IPC measures, the early detection of cases through the screening of residents and staff is essential to identify asymptomatic and pre-symptomatic cases and limit the spread of the virus.

Resource partitioning is a mechanism for niche differentiation which can facilitate coexistence of species at local scales. Insights into resource use and niche differentiation of functionally similar and/or taxonomically closely related species are scant, especially so for small organisms that dominate marine sediments in terms of abundance and species richness. In this study we characterized the microbiomes of 10 bacterivorous nematode species co-occurring in various estuarine microhabitats using 16S rRNA metabarcoding to address their resource utilization. We investigated microbiome diversity and composition of nematodes collected from six microhabitats in the field: Fucus spiralis, Fucus vesiculosus, fresh and decomposing thalli of Ulva sp., and attached and detached leaves of Spartina anglica. The 10 species belonged to three different families, and included congeneric and morphologically cryptic species. The microbiome of species sharing their microhabitats showed a substantial overlap, suggesting that resource differentiation of species within a microhabitat was rather limited at time of sampling. Microbiomes of the same nematode species found in different microhabitats were also not strongly differentiated. Temporal divergence in resource use may occur, as suggested by temporally divergent microbiome composition of nematodes associated with Ulva sp. The observed high intraspecific variability in microbiome composition of nematodes may be the principal factor explaining the lack of microbiome differentiation among species or microhabitats and may illustrate individual specialization in resource use as a consequence of substantial intraspecific competition.

Differences in resource use or in tolerances to abiotic conditions are often invoked as potential mechanisms underlying the sympatric distribution of cryptic species. Additionally, the microbiome can provide physiological adaptations of the host to environmental conditions. We determined the intra- and interspecific variability of the microbiomes of three cryptic nematode species of the Litoditis marina species complex that co-occur, but show differences in abiotic tolerances. Roche 454 pyrosequencing of the microbial 16S rRNA gene revealed distinct bacterial communities characterized by a substantial diversity (85-513 OTUs) and many rare OTUs. The core microbiome of each species contained only very few OTUs (2-6), and four OTUs were identified as potentially generating tolerance to abiotic conditions. A controlled experiment in which nematodes from two cryptic species (Pm1 and Pm3) were fed with either an E. coli suspension or a bacterial mix was performed, and the 16S rRNA gene was sequenced using the MiSeq technology. OTU richness was 10-fold higher compared to the 454 data set and ranged between 1118 and 7864. This experiment confirmed the existence of species-specific microbiomes, a core microbiome with few OTUs, and high interindividual variability. The offered food source affected the bacterial community and illustrated different feeding behaviour between the cryptic species, with Pm3 exhibiting a higher degree of selective feeding than Pm1. Morphologically similar species belonging to the same feeding guild (bacterivores) can thus have substantial differences in their associated microbiomes and feeding strategy, which in turn may have important ramifications for biodiversity-ecosystem functioning relationships.

The responsibilities of today's educational institutions far exceed basic education. Aside from academics, schools are also responsible for developing citizens who can identify and rectify social injustices. Preparing students to engage in transformative practice requires student-centered classrooms wherein students first reflect on themselves and become aware of their belief systems, and then take ownership of their own learning by means of choice and decision making. The goal is for students to develop critical thinking skills that will carry over into their evaluations of the world as a whole and the choices that they make to initiate social change.

L’œnotourisme s’est développé, en premier lieu, dans ce que l’on appelle les « nouveaux vignobles » (Lignon-Darmaillac, 2014). Cet outil a permis à ces régions de revenir dans la course du « marché des réputations » (Chauvin, 2010), en transformant leur image, créant ainsi des destinations œnotouristiques, se réappropriant le produit culturel qu’est le vin en le transformant en outil d’attractivité. Repris à la fin du XX° siècle par les pays européens, le tourisme viti-vinicole prend des formes diverses, en fonction des vignobles. Les objectifs ne sont pas les mêmes, certains vignobles l’utilisent pour renforcer leur attractivité et augmenter les ventes, d’autres pour diffuser un imaginaire et conforter leur place dans la hiérarchie des vignobles mondiaux et nationaux.En Bourgogne, malgré la réputation de certains vignobles de la région, l’œnotourisme peut être un outil intéressant, dans des dimensions et objectifs différents. Si l’image des vins de la région à travers le monde ne cesse de croître, tous les vignobles de la région ne sont pas égaux. Ainsi, les grands vins de la Côte de Nuits et de la Côte de Beaune font office de porte-parole de renom, laissant derrière eux des vignobles qui n’écoulent pas encore leur production au même rythme, ni aux mêmes prix. Ce sont ces vignobles qui vont développer un intérêt important pour l’œnotourisme, dans l’objectif de renforcer leurs ventes, leur image et de créer une destination touristique centrée autour de vignobles moins renommés mais plus faciles d’accès.Mais l’œnotourisme est également un outil essentiel pour la Côte de Nuits et la Côte de Beaune, de par son pouvoir de diffusion d’un imaginaire (Amirou, 2012), socialement construit. Grâce à cette forme touristique, sa compatibilité et sa complémentarité avec l’éco-tourisme, en plein essor, c’est l’ensemble d’un vignoble qui y trouve son compte, diffusant une image où les critères de qualité, d’authenticité, de tradition, trouvent leur légitimité auprès du consommateur et du touriste.Au sein d’une même région viticole, l’œnotourisme peut donc être un moyen de répondre à la hiérarchisation des vignobles, permettant aux acteurs les moins médiatisés de renforcer leurs ventes et leur attractivité. Dans la même logique que celle qui a amené à sa création dans les vignobles du nouveau monde, l’œnotourisme est un moyen pour les vignobles les plus « modestes », d’exister face aux « mastodontes » (à l’échelle internationale, nationale et régionale).À partir d’exemples bourguignons, il sera question d’envisager cette dialectique régionale, faisant écho aux logiques ayant contribué à l’émergence de ce phénomène touristique en plein essor. Car c’est également le reflet des tensions qui animent la Bourgogne, ses vignobles et ses différents territoires viticoles, dont l’homogénéité n’est qu’une question de nom.L’œnotourisme se développe dans un premier temps sur les territoires les plus attractifs, ceux qui jouissent d’une réputation internationale, les vignobles de Côte d’Or principalement, regroupant 32 des 33 grands crus. Cependant, ces vignobles n’ayant que peu besoin de cet outil, les initiatives sont restreintes et les touristes frustrés de n’avoir accès aux domaines les plus prestigieux.À l’inverse, d’autres vignobles bourguignons, qui ne bénéficient pas de la même réputation, voient en cette nouvelle forme touristique l’opportunité de construire un « imaginaire », par lequel ils pourront rééquilibrer leur place dans le marché des réputations. Les initiatives sont plus nombreuses et surtout, une place plus importante leur revient. Pourtant, il n’est pas évident d’attirer les touristes qui veulent découvrir les climats les plus renommés. Mais le dynamisme, l’imaginaire, la production et les prix sont autant d’arguments qui vont permettre l’émergence des activités dans ces territoires.Ces deux modèles régionaux permettront de mettre en avant les deux facettes de l’œnotourisme. Les exemples, issus du recueil de données qualitatives à travers des entretiens et observations, montrent que ce tourisme viti-vinicole est un outil marketing qui ne se limite pas aux acteurs les plus « modestes » en termes de réputation.En s’intéressant aux professionnels de l’œnotourisme, à travers son émergence en Bourgogne, et les formes spécifiques qui en découlent, on analyse donc un phénomène touristique complexe, socle d’un monde social au sein duquel se tissent des relations d’interdépendance, ce que l’on nomme des écologies liées (Abbott, 2003). Les enjeux de ce tourisme viti-vinicole sont au cœur des projets des territoires et son rôle dépasse les prénotions communément partagées. En prenant appui sur l’image du vignoble, développée notamment à travers les actions d’acteurs tels que la Confrérie des Chevaliers du Tastevin dans les années 1930 (Jacquet & Laferté, 2014), l’œnotourisme devient petit à petit l’expression d’un vignoble, celle qui se propage dans le monde et diffuse la figure de la culture viticole de la région. Il semble donc que ce soit un tournant dans l’histoire de ce phénomène, dont l’importance pourrait encore augmenter dans les années à venir, de par sa double utilité, que nous évoquerons. L’œnotourisme est donc un enjeu politique et économique aux répercussions multiples mais surtout aux avantages divers, qui concernent une palette hétérogène d’acteurs du secteur viticole et touristique. En profitant de l’image qui se diffuse en partie par le biais de l’œnotourisme, des vignobles moins attractifs pourraient bien développer une offre plus à même de répondre à la demande de ce marché en plein essor. Grâce à cet outil, ces vignobles peuvent mettre en scène leurs territoires et développer une offre touristique complète, profitant de l’image socialement construite et portée par l’œnotourisme.

Worldwide, primates, and humans increasingly share habitats and often enter in conflict when primates thrive in human-dominated environments, calling for special management measures. Reproductive control is increasingly used to manage population growth but very few monitoring data are available. Therefore, the efficiency and implications of such programs require a careful examination. In the context of a contraception program in wild female long-tailed macaques in Ubud, Bali, conducted over four successive campaigns between 2017 and 2019, including 140 females (i.e., 41.9% of the reproductive females of the population in 2019), modifications of an endoscopic tubectomy procedure, a permanent sterilization method, clinical evaluation of this method, and the post-operative monitoring results of the neutered females after release are described. This surgical approach was applicable for pregnant females: 28.6% of the treated females were pregnant at the time of the surgery. The procedure used a single lateral port to reach and cauterize both oviducts in non-pregnant as well as in early to mid-term pregnant females. Pregnant females nearer to term required a second lateral port to access both oviducts masked by the size of the gravid uterus. Moreover, bipolar thermocauterization was utilized successfully without resection to realize the tubectomy. The average duration of the laparoscopic surgery was 14 min for non-pregnant females and 22 min for pregnant females. Animals were released 3 h 22 min in average following their capture. This short holding time, recommended for free-ranging primates, was made possible by the minimal invasiveness of the sterilization approach. A laparoscopic post-operative evaluation conducted on two patients during the following campaign confirmed that the oviducts were definitely disrupted and no longer patent. Moreover, no new pregnancies in sterilized females were recorded during the 3-year observation period. The survival rate of the treated females 6 months after sterilization was high (96.3%) with no major post-operative complications clinically recorded. Among females that were pregnant during surgery, 81.1% were confirmed to experience term delivery. This study demonstrates the safety and efficiency of endoscopic tubectomy, even for pregnant females, as a mean of wild macaques' population control.

File names are one of the earliest computing abstractions, a string of characters to uniquely identify a file for the system, and to help users remember the contents when they look for it later. They are also a rich source of semantic metadata about files. However, this metadata is unstructured and opaque to the rest of the system. As a result, metadata in file names is often error-prone, and hard to search for. File names can and should be more meaningful and reliable, while simplifying application design and encouraging users and applications to provide more metadata for search. We describe a POSIX compliant prototype file system, TrueNames, which demonstrates an alternate approach to naming and metadata, called metadata aware naming. TrueNames separates the task of uniquely identifying a file from the task of helping the user remember its contents. It captures metadata in a structured format for later indexing, and uses it to generate file names which are correct, regenerable, and disambiguatable by design. TrueNames simplifies application design by providing a consistent interface for metadata aware naming, incurs a low overhead of approximately 15[%] under realistic workloads, and can simplify a wide variety of data management tasks for both applications and users.