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Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with k inact /K I  = 9,600 M −1 s −1 , achieves sub-μM EC 50 values against three SARS-CoV-2 variants in mammalian cell lines, and does not inhibit a panel of human deubiquitinases (DUBs) at >30 μM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validates our design strategy and establishes the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors. The development of direct-acting antivirals to combat COVID-19 remains an important goal. Here the authors design covalent inhibitors that target the papain-like protease from SARS-CoV-2. The most promising inhibitor blocks viral replication in mammalian cells.

Climate change causes significant alterations in precipitation and temperature regimes that are predicted to become more extreme throughout the next century. Microorganisms are important members within ecosystems, and how they respond to these changing abiotic stressors has large implications for the functioning of ecosystems, the recycling of nutrients, and the health of the aboveground plant community. Drought stress negatively impacts microbial activity, but the magnitude of this stress response may be dependent on above- and belowground interactions. This study demonstrates that beneficial associations between plants and microbes can enhance tolerance to abiotic stress. Drought stress negatively impacts microbial activity, but the magnitude of stress responses is likely dependent on a diversity of belowground interactions. Populus trichocarpa individuals and no-plant bulk soils were exposed to extended drought (∼0.03% gravimetric water content [GWC] after 12 days), rewet, and a 12-day “recovery” period to determine the effects of plant presence in mediating soil microbiome stability to water stress. Plant metabolomic analyses indicated that drought exposure increased host investment in C and N metabolic pathways (amino acids, fatty acids, phenolic glycosides) regardless of recovery. Several metabolites positively correlated with root-associated microbial alpha-diversity, but not those of soil communities. Soil bacterial community composition shifted with P. trichocarpa presence and with drought relative to irrigated controls, whereas soil fungal composition shifted only with plant presence. However, root fungal communities strongly shifted with drought, whereas root bacterial communities changed to a lesser degree. The proportion of bacterial water-stress opportunistic operational taxonomic units (OTUs) (enriched counts in drought) was high (∼11%) at the end of drying phases and maintained after rewet and recovery phases in bulk soils, but it declined over time in soils with plants present. For root fungi, opportunistic OTUs were high at the end of recovery in drought treatments (∼17% abundance), although relatively not responsive in soils, particularly planted soils (<0.5% abundance for sensitive or opportunistic). These data indicate that plants modulate soil and root-associated microbial drought responses via tight plant-microbe linkages during extreme drought scenarios, but trajectories after extreme drought vary with plant habitat and microbial functional groups. IMPORTANCE Climate change causes significant alterations in precipitation and temperature regimes that are predicted to become more extreme throughout the next century. Microorganisms are important members within ecosystems, and how they respond to these changing abiotic stressors has large implications for the functioning of ecosystems, the recycling of nutrients, and the health of the aboveground plant community. Drought stress negatively impacts microbial activity, but the magnitude of this stress response may be dependent on above- and belowground interactions. This study demonstrates that beneficial associations between plants and microbes can enhance tolerance to abiotic stress.

ABSTRACT Drought stress negatively impacts microbial activity, but the magnitude of stress responses is likely dependent on a diversity of belowground interactions. Populus trichocarpa individuals and no-plant bulk soils were exposed to extended drought (∼0.03% gravimetric water content [GWC] after 12 days), rewet, and a 12-day “recovery” period to determine the effects of plant presence in mediating soil microbiome stability to water stress. Plant metabolomic analyses indicated that drought exposure increased host investment in C and N metabolic pathways (amino acids, fatty acids, phenolic glycosides) regardless of recovery. Several metabolites positively correlated with root-associated microbial alpha-diversity, but not those of soil communities. Soil bacterial community composition shifted with P. trichocarpa presence and with drought relative to irrigated controls, whereas soil fungal composition shifted only with plant presence. However, root fungal communities strongly shifted with drought, whereas root bacterial communities changed to a lesser degree. The proportion of bacterial water-stress opportunistic operational taxonomic units (OTUs) (enriched counts in drought) was high (∼11%) at the end of drying phases and maintained after rewet and recovery phases in bulk soils, but it declined over time in soils with plants present. For root fungi, opportunistic OTUs were high at the end of recovery in drought treatments (∼17% abundance), although relatively not responsive in soils, particularly planted soils (<0.5% abundance for sensitive or opportunistic). These data indicate that plants modulate soil and root-associated microbial drought responses via tight plant-microbe linkages during extreme drought scenarios, but trajectories after extreme drought vary with plant habitat and microbial functional groups. IMPORTANCE Climate change causes significant alterations in precipitation and temperature regimes that are predicted to become more extreme throughout the next century. Microorganisms are important members within ecosystems, and how they respond to these changing abiotic stressors has large implications for the functioning of ecosystems, the recycling of nutrients, and the health of the aboveground plant community. Drought stress negatively impacts microbial activity, but the magnitude of this stress response may be dependent on above- and belowground interactions. This study demonstrates that beneficial associations between plants and microbes can enhance tolerance to abiotic stress.

Numerous agronomical applications of remote sensing have been proposed in recent years, including water stress assessment at field by thermal imagery. The miniaturization of thermal cameras allows carrying them onboard the unmanned aerial vehicles (UAVs), but these systems have no temperature control and, consequently, drifts during data acquisition have to be carefully corrected. This manuscript presents a comprehensive methodology for radiometric correction of UAV remotely-sensed thermal images to obtain (combined with visible and near-infrared data) multispectral ortho-mosaics, as a previous step for further image-based assessment of tree response to water stress. On summer 2013, UAV flights were performed over an apple tree orchard located in Southern France, and 4 dates and 5 h of the day were tested. The 6400 m 2 field plot comprised 520 apple trees, half well-irrigated and half submitted to progressive summer water stress. Temperatures of four different on-ground stable reference targets were continuously measured by thermo-radiometers for radiometric calibration purposes. By using self-developed software, frames were automatically extracted from the thermal video files, and then radiometrically calibrated using the thermal targets data. Once ortho-mosaics were obtained, root mean squared error (RMSE) was calculated. The accuracy obtained allowed multi-temporal mosaic comparison. Results showed a good relationship between calibrated images and on-ground data. Significantly higher canopy temperatures were found in water-stressed trees compared to well-irrigated ones. As high resolution field ortho-mosaics were obtained, comparison between trees opens the possibility of using multispectral data as phenotypic variables for the characterization of individual plant response to drought.

Bien que la jalousie soit reliée négativement au bien-être individuel et conjugal, peu d'instruments validés en langue française sont disponibles. Cet article présente la traduction de la Multidimensional Jealousy Scale (Pfeiffer & Wong, 1989) et la validation de l'Échelle multidimensionnelle de jalousie, un questionnaire évaluant les dimensions cognitive, affective et comportementale de la jalousie en 24 items. Les qualités psychométriques du questionnaire sont évaluées auprès de deux échantillons indépendants. Dans l'Étude 1 (N = 300), une analyse factorielle exploratoire suggère une structure tridimensionnelle du questionnaire abrégé en 15 items. La validité critériée et la fidélité (cohérence interne) sont également examinées. Dans l'Étude 2 (N = 381), des analyses factorielles confirmatoires appuient la structure tridimensionnelle de la version en 15 items. Ces résultats soutiennent l'utilisation de l'Échelle multidimensionnelle de jalousie en 15 items. While jealousy has a negative link to individual and conjugal well-being, few valid French-language instruments are available. This article presents a translation of the Multidimensional Jealousy Scale (Pfeiffer & Wrong, 1989) and the validation of its French version, Échelle multidimensionnelle de jalousie, a 24-item questionnaire evaluating the cognitive, affective and behavioural dimensions of jealousy. Psychometric qualities of the questionnaire are evaluated through two independent samples. In Study 1 (N = 300), exploratory factorial analysis suggests a three-dimensional structure of an abridged questionnaire of 15 items. Criterion related validity and fidelity (internal consistency) are also examined. In Study 2 (N = 381), confirmatory factorial analyses support the three-dimensional structure of the 15-item version. These results support the use of a 15-item multidimensional jealousy scale. Intérêt public Dans une relation de couple, la jalousie peut se manifester de trois façons : des pensées envers la perte possible du partenaire, des émotions ou sentiments jaloux, et des comportements comme la vérification. Cette étude a permis de traduire en français un questionnaire évaluant ces trois facettes de la jalousie amoureuse. Les résultats montrent qu'une version en 15 items de cet outil semble bien évaluer la jalousie amoureuse chez les adultes.

Trois études ont été menées pour élaborer et valider le nouveau Questionnaire multimodal d'engagement conjugal (QMEC). L'Étude 1 a permis de créer et d'évaluer la structure factorielle de la première version en 45 items du questionnaire à l'aide d'un échantillon de 139 adultes. Dans l'Étude 2, des analyses factorielles exploratoires ont permis de réduire le nombre d'items du questionnaire à l'aide d'un échantillon de 317 adultes de la communauté. Dans l'Étude 3, les qualités psychométriques du QMEC en 27 items ont été démontrées au sein d'un vaste échantillon de 797 adultes en utilisant l'analyse factorielle confirmatoire. Les résultats montrent que le QMEC est une mesure prometteuse de l'engagement optimal, du surengagement et du sous-engagement conjugal qui peut être utilisée avec confiance par les chercheurs. D'autres études de validation sont nécessaires pour son utilisation en contexte clinique. Three studies were conducted to develop and validate the new multimodal couple commitment questionnaire (MCCQ). Study 1 led to the creation and evaluation of the factor structure of the first version in 45 items of the questionnaire, with a sample of 139 adults. In Study 2, exploratory factor analyses among 317 adults from the community helped to reduce the number of items in the questionnaire. In Study 3, confirmatory factor analysis was used within a broad sample of 797 adults to demonstrate the psychometric qualities of the Questionnaire in 27 items. The results showed that MCCQ is a promising measure of optimal commitment, of over-commitment and of under-commitment that researchers can use with confidence. Further validation studies are needed to enable its use in a clinical context.