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  • COVID-19
  • French National Research Agency (ANR)
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Charlotte Lombardi; Maya Ayach; Lionel Beaurepaire; Mélanie Chenon; +4 Authors

    Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction. Author Summary Positive-stranded RNA viruses are ultimate parasites. In order to replicate their genome, they first need to invade a host cell and, with usually very limited viral genetic material, subvert the host's molecular machinery. Turnip yellow mosaic virus (TYMV) is an excellent model system for studying positive-stranded RNA virus replication. As for many such viruses, TYMV genome replication is dependent on the activity of a viral proteinase (PRO) to properly process the virus' replication molecules. We have recently established that PRO is a multifunctional enzyme and is also used by TYMV to subvert a key host defense against pathogens. We report here the atomic structure of PRO as well as new functional data on PRO's interaction with the host. Our data shed light on how PRO can perform such multiple activities despite its small size, providing TYMV with a Swiss army knife in its ongoing fight with a vastly more complex host.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2013
    Data sources: PubMed Central
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    PLoS Pathogens
    Article . 2013
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    PLoS Pathogens
    Article . 2013 . Peer-reviewed
    License: CC BY
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    PLoS Pathogens
    Article . 2013
    Data sources: DOAJ-Articles
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    PLoS Pathogens
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      Europe PubMed Central
      Article . 2013
      Data sources: PubMed Central
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      PLoS Pathogens
      Article . 2013
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      PLoS Pathogens
      Article . 2013 . Peer-reviewed
      License: CC BY
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      PLoS Pathogens
      Article . 2013
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      PLoS Pathogens
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    Authors: Kavousi, Javid; Goudarzi, Forough; Izadi, Mohammad; Gardner, Charlie J.;

    International audience; The conservation of biodiversity-and the vital ecosystem services it generates-is one of the greatest challenges humanity faces, yet the field faces drastic funding cuts as society realigns its priorities in the face of the COVID-19 pandemic. Here, we argue that diverting attention from conservation would, however, increase the risk of further global health crises because the emergence of novel infectious diseases is partially driven by global environmental change. As the discrepancy between conservation needs and society's willingness to pay for them grows, conservation will have to evolve to stay relevant in the age global change-induced human infectious disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Global Change Biolog...arrow_drop_down
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    Global Change Biology
    Article . 2020 . Peer-reviewed
    License: Wiley Online Library User Agreement
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    Hal-Diderot
    Article . 2020
    Data sources: Hal-Diderot
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Global Change Biolog...arrow_drop_down
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      Global Change Biology
      Article . 2020 . Peer-reviewed
      License: Wiley Online Library User Agreement
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Hal-Diderot
      Article . 2020
      Data sources: Hal-Diderot
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lindamulage de Silva, Olivier; Lasaulce, Samson; Morarescu, Irinel-Constantin;

    National audience; Dans cet article, nous introduisons un modèle de jeu qui permet d'évaluer la potentielle perte d'efficacité induite par un contrôle décentralisé d'une épidémie. Chaque joueur représente une région ou un pays qui est supposé choisir son action de contrôle pour mettre en oeuvre un compromis local entre les aspects socio-économiques et l'aspect sanitaire. Nous effectuons l'analyse de l'équilibre de Nash de ce jeu. Nous quantifions ensuite par des résultats numériques la perte induite par une prise de décision décentralisé en termes de prix de l'anarchie (PoA). Ces résultats permettent d'identifier clairement les scénarios où la décentralisation est acceptable ou non au regard des mesures d'efficacité globale retenues.

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    Other literature type . 2022
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      Other literature type . 2022
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    Authors: Stéphane Raffard; Sophie Bayard; Margot Eisenblaetter; Philippe Tattard; +3 Authors

    International audience; Recent evidence suggests that people with schizophrenia are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Capacity to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished capacity to consent to the vaccination. Diminished capacity to consent to COVID-19 vaccination was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ https://www.medrxiv....arrow_drop_down
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    https://www.medrxiv.org/conten...
    Preprint
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    European Archives of Psychiatry and Clinical Neuroscience
    Article . 2022 . Peer-reviewed
    License: Springer Nature TDM
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      European Archives of Psychiatry and Clinical Neuroscience
      Article . 2022 . Peer-reviewed
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    Authors: Baunez, Christelle; Degoulet, Mickaël; Luchini, Stéphane; Pintus, Patrick A.; +1 Authors

    Even though much has been learned about the new pathogen SARS-CoV-2 since the beginning of the COVID-19 pandemic, a lot of uncertainty remains. In this paper we argue that what is important to know under uncertainty is whether harm accelerates and whether health policies achieve deceleration of harm. For this, we need to see cases in relation to diagnostic effort and not to look at indicators based on cases only, such as a number of widely used epidemiological indicators, including the reproduction number, do. To do so overlooks a crucial dimension, namely the fact that the best we can know about cases will depend on some welldefined strategy of diagnostic effort, such as testing in the case of COVID-19. We will present a newly developed indicator to observe harm, the acceleration index, which is essentially an elasticity of cases in relation to tests. We will discuss what efficiency of testing means and propose that the corresponding health policy goal should be to find ever fewer cases with an ever-greater diagnostic effort. Easy and low-threshold testing will also be a means to give back people’s sovereignty to lead their life in an “open” as opposed to “locked-down” society.

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    Other literature type . 2021
    SSRN Electronic Journal
    Article . 2021 . Peer-reviewed
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      Other literature type . 2021
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      Article . 2021 . Peer-reviewed
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    Authors: Di Domenico, Laura; Pullano, Giulia; Sabbatini, Chiara E.; Boëlle, Pierre-Yves; +1 Authors

    As countries in Europe implement strategies to control the COVID-19 pandemic, different options are chosen regarding schools. Through a stochastic age-structured transmission model calibrated to the observed epidemic in Île-de-France in the first wave, we explored scenarios of partial, progressive, or full school reopening. Given the uncertainty on children’s role, we found that reopening schools after lockdown may increase COVID-19 cases, yet protocols exist to keep the epidemic controlled. Under a scenario with stable epidemic activity if schools were closed, reopening pre-schools and primary schools would lead to up to 76% [67, 84]% occupation of ICU beds if no other school level reopened, or if middle and high schools reopened later. Immediately reopening all school levels may overwhelm the ICU system. Priority should be given to pre- and primary schools allowing younger children to resume learning and development, whereas full attendance in middle and high schools is not recommended for stable or increasing epidemic activity. Large-scale test and trace is required to keep the epidemic under control. Ex-post assessment shows that progressive reopening of schools, limited attendance, and strong adoption of preventive measures contributed to a decreasing epidemic after lifting the first lockdown. The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system.

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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
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    Nature Communications
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    Nature Communications
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      Europe PubMed Central
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    Authors: Mathieu Bourgarel; Davies M. Pfukenyi; Vanina Boué; Loïc Talignani; +6 Authors

    Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus. Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential. Highlights • Coronavirus and Paramyxovirus circulate in Hipposideros bat species in Zimbabwe. • Importance of widening viral screening in under-investigated countries • Sentinel surveillance in sites with high zoonotic transmission potential

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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Infection, Genetics and Evolution
    Article . 2018 . Peer-reviewed
    License: Elsevier TDM
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    Horizon / Pleins textes
    Other literature type . 2018
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Article . 2018
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      Europe PubMed Central
      Article . 2018
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      Infection, Genetics and Evolution
      Article . 2018 . Peer-reviewed
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      Horizon / Pleins textes
      Other literature type . 2018
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Claude Pasquier; Alain Robichon;

    The role of the RNAi/Dicer/Ago system in degrading RNA viruses has been elusive in mammals in the past, which has prompted authors to think that interferon (IFN) synthesis is essential in this clade, relegating the RNAi defense strategy against viral infection as an accessory function. However, recent publications highlight the existence of abundant viral small interference and micro RNAs (VsiRNAs and VmiRNAs) in both cell-line and whole organism based experiments, indicating a contribution of these molecules in host responses and/or viral replication. We explore the theoretical possibility that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction, although this hypothesis seems counterintuitive. The SARS-CoV-2 genome was therefore computationally searched for exact intrapairing within the viral RNA and exact hybrid pairing with the human transcriptome over a minimum of 20 bases in length. Minimal segments of 20-base lengths of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, including mitochondrial deubiquitinase USP30, the subunit of ubiquitin protein ligase complex FBXO21 and two long noncoding RNAs, were retrieved. The hypothesis that viral-originated RNAi might mediate degradation of host transcriptome messages was corroborated by published high throughput sequencing of RNA from infected tissues and cultured cells, clinical observation and phylogenetic comparative analysis, indicating a strong specificity of these SARS-CoV-2 hybrid pairing sequences for human genomes. SARS-CoV-2; dsRNA; Dicer; RNA cleavage; Host transcriptome; Viral genome.

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    Europe PubMed Central
    Article . 2021
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    Heliyon
    Article . 2021
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    Hal-Diderot
    Article . 2021
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    Preprint . 2020
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      Europe PubMed Central
      Article . 2021
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      Article . 2021
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    Authors: Fillâtre, Pierre; Dufour, Marie-José; Behillil, Sylvie; Vatan, Remi; +24 Authors

    Objectives In early January 2021, an outbreak of nosocomial cases of COVID-19 emerged in Western France, with RT-PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS-CoV-2 lineage: B.1.616. In March, WHO classified this variant as ‘under investigation’ (VUI). We analyzed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled inpatients with either: i) positive SARS-CoV-2 RT-PCR on a respiratory sample; ii) seroconversion with anti-SARS-CoV-2 IgG/IgM; iii) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown. Results From January 1st to March 24th, 2021, 114 patients fulfilled inclusion criteria: B.1.616 (n=39), VOC (n=32), and unknown (n=43). B.1.616-related cases were older than VOC-related cases (81 years interquartile range [IQR] [73-88], vs 73 years IQR [67-82], P<0.05) and their first RT-PCR tests were rarely positive (6/39, 15% vs 31/32, 97%, P<0.05). B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0 95% CI [1.5-10.9]), and increased lethality: 28-day mortality 18/39 (46%) for B.1.616, vs. 5/32 (16%) for VOC, P=0.006. Conclusion We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, poorly detected by RT-PCR on nasopharyngeal samples, with high lethality. Graphical abstract Image 1

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    Europe PubMed Central
    Article . 2021
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    Hal-Diderot
    Article . 2021
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    Other literature type . 2022
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    Authors: Chanel, Olivier; Prati, Alberto; Raux, Morgan;

    International audience; We provide an estimate of the environmental impact of the recruitment system in the economics profession, known as the “international job market for economists”. Each year, most graduating PhDs seeking jobs in academia, government, or companies participate in this job market. The market follows a standardized process, where candidates are pre-screened in a short interview which takes place at an annual meeting in Europe or in the United States. Most interviews are arranged via a non-profit online platform, econjobmarket.org, which kindly agreed to share its anonymized data with us. Using this dataset, we estimate the individual environmental impact of 1057 candidates and one hundred recruitment committees who attended the EEA and AEA meetings in December 2019 and January 2020. We calculate that this pre-screening system generated the equivalent of about 4800 tons of avoidable CO2-eq and a comprehensive economic cost over €4.4 million. We contrast this overall assessment against three counterfactual scenarios: an alternative in-person system, a hybrid system (where videoconference is used for some candidates) and a fully online system (as it happened in 2020–21 due to the COVID-19 pandemic). Overall, the study can offer useful information to shape future recruitment standards in a more sustainable way.

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    Ecological Economics
    Article . 2022 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Ecological Economics
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    Authors: Charlotte Lombardi; Maya Ayach; Lionel Beaurepaire; Mélanie Chenon; +4 Authors

    Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction. Author Summary Positive-stranded RNA viruses are ultimate parasites. In order to replicate their genome, they first need to invade a host cell and, with usually very limited viral genetic material, subvert the host's molecular machinery. Turnip yellow mosaic virus (TYMV) is an excellent model system for studying positive-stranded RNA virus replication. As for many such viruses, TYMV genome replication is dependent on the activity of a viral proteinase (PRO) to properly process the virus' replication molecules. We have recently established that PRO is a multifunctional enzyme and is also used by TYMV to subvert a key host defense against pathogens. We report here the atomic structure of PRO as well as new functional data on PRO's interaction with the host. Our data shed light on how PRO can perform such multiple activities despite its small size, providing TYMV with a Swiss army knife in its ongoing fight with a vastly more complex host.

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    Europe PubMed Central
    Article . 2013
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    PLoS Pathogens
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    PLoS Pathogens
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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