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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: Camille Aubry; Sinéad C. Corr; Sebastian Wienerroither; Céline Goulard; +6 Authors

    PUBLISHED Synthesis of interferon-? (IFN-?) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-? synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-? production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ?pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-? gene, requiring TLR2 and bacterial internalization. Induction of IFN-? was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-? gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-? gene expression. Work in PC's laboratory received financial support from Institut Pasteur (http://www.pasteur.fr), Inserm (http://www.inserm.fr), INRA (http://www.inra.fr), ERC (Advanced Grant 233348, http://erc.europa.eu/), Fondation Pasteur-Weizmann and Fondation le Roch Les Mousquetaires (http://www.fondationleroch-lesmousquetai?res.org/). PC is an international research scholar of the Howard Hughes Medical Institute (http://www.hhmi.org/). CA is a doctoral fellow of the Ministere de l'Enseignement Superieur et de la Recherche. Work in LO's laboratory was supported by Science Foundation Ireland (http://www.sfi.ie/) and the Irish Research Council for Science, Engineering and Technology (RS/2005/190, http://www.ircset.ie/). Work in TD's laboratory was funded by the Austrian Research Foundation (grants SFB-28 and P20522-B05, http://www.fwf.ac.at). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    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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    PLoS ONE
    Article . 2012
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    ProdInra
    Article . 2012
    License: CC BY SA
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    PLoS ONE
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    Article . 2012
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      Article . 2012
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      ProdInra
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      PLoS ONE
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      Article . 2012
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    Authors: Burger, Pamela Anna; Ciani, Elena; Faye, Bernard;

    SummaryOld World camels have served humans in cross‐continental caravans, transporting people and goods, connecting different cultures and providing milk, meat, wool and draught since their domestication around 3000–6000 years ago. In a world of modern transport and fast connectivity, these beasts of burden seem to be out‐dated. However, a growing demand for sustainable milk and meat production, especially in countries affected by climate change and increasing desertification, brings dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus) back onstage and into the focus of animal breeders and scientists. In this review on the molecular genetics of these economically important species we give an overview about the evolutionary history, domestication and dispersal of Old World camels, whereas highlighting the need for conservation of wild two‐humped camels (Camelus ferus) as an evolutionarily unique and highly endangered species. We provide cutting‐edge information on the current molecular resources and on‐going sequencing projects. We cannot emphasise enough the importance of balancing the need for improving camel production traits with maintaining the genetic diversity in two domestic species with specific physiological adaptation to a desert environment.

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    Animal Genetics
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    Animal Genetics; OpenAPC Global Initiative
    Article . Conference object . 2019 . Peer-reviewed
    License: CC BY
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      Animal Genetics
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      Animal Genetics; OpenAPC Global Initiative
      Article . Conference object . 2019 . Peer-reviewed
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    Authors: Mélanie Bourgin; Lisa Derosa; Carolina Alves Costa Silva; Anne-Gaëlle Goubet; +12 Authors

    International audience; Cancer patients are particularly susceptible to the development of severe Covid-19, prompting us to investigate the serum metabolome of 204 cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive tryptophan/kynurenine metabolite anthranilic acid correlates with poor prognosis in non-cancer patients. In cancer patients, we observed an elevation of anthranilic acid at baseline (without Covid-19 diagnosis) and no further increase with mild or severe Covid-19. We found that, in cancer patients, Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory cytokines. Most importantly, we observed that the levels of acetylated polyamines (in particular N1-acetylspermidine, N1,N8-diacetylspermidine and N1,N12-diacetylspermine), alone or in aggregate, were elevated in severe Covid-19 cancer patients requiring hospitalization as compared to uninfected cancer patients or cancer patients with mild Covid-19. N1-acetylspermidine and N1,N8-diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated polyamines increase in the serum from patients with cancer, cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated polyamines are associated with severe Covid-19, both in the general population and in patients with malignant disease. Severe Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of spermine/spermidine N1-acetyl transferase-1 (SAT1), which catalyzes the first step of polyamine catabolism.

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    Aging
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    Authors: Carmona-Gutierrez, Didac; Bauer, Maria,; Zimmermann, Andreas; Kainz, Katharina; +3 Authors

    International audience; Autophagy is a catabolic pathway with multifaceted roles in cellular homeostasis. This process is also involved in the antiviral response at multiple levels, including the direct elimination of intruding viruses (virophagy), the presentation of viral antigens, the fitness of immune cells, and the inhibition of excessive inflammatory reactions. In line with its central role in immunity, viruses have evolved mechanisms to interfere with or to evade the autophagic process, and in some cases, even to harness autophagy or constituents of the autophagic machinery for their replication. Given the devastating consequences of the current COVID-19 pandemic, the question arises whether manipulating autophagy might be an expedient approach to fight the novel coronavirus SARS-CoV-2. In this piece, we provide a short overview of the evidence linking autophagy to coronaviruses and discuss whether such links may provide actionable targets for therapeutic interventions.

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    Microbial Cell
    Article . 2020 . Peer-reviewed
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    Microbial Cell
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    Microbial Cell
    Article . 2020
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      Microbial Cell
      Article . 2020 . Peer-reviewed
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      Microbial Cell
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    Authors: Jaber-Lopez, Tarek; Blanco, Esther; Baier, Alexandra; Holzmeister, Felix; +1 Authors

    Abstract Think tanks and political leaders have raised concerns about the implications that the Covid-19 response and reconstruction might have on other social objectives that were setting the international agenda before the Covid-19 pandemic. We present evidence for eight consecutive weeks during April–May 2020 for Austria, testing the extent to which Covid-19 concerns substitute other social concerns such as the climate crisis or the protection of vulnerable sectors of the society. We measure behavior in a simple donation task where participants receive €3 that they can distribute between themselves and a list of charitable organizations, which vary between treatments. We consider initially a list of eight charities, including a broad set of social concerns. Results show that introducing the WHO Covid-19 Solidarity Response Fund significantly reduces the sum of donations to the original eight charities. This derives from two effects: First, introducing the Covid-19 Solidarity Response Fund does not significantly change aggregate donations. Second, results point to a high support to the WHO Covid-19 Fund. Overall, our results indicate that donations to diverse social concerns are partially substituted by donations to the Covid-19 fund; yet, this substitution does not fully replace all other social concerns. Results are robust to a 10-fold increase in endowment, with decisions made over €30.

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    Ecological Economics
    Article . 2022 . Peer-reviewed
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    Authors: Stiasny, Karin; Kössl, Christian; Lepault, Jean; Rey, Félix A.; +1 Authors

    Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E) mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion. Author Summary The fusion of cellular lipid membranes is an essential process in all forms of life. Such membranes are also part of a specific structural class of viruses—so-called enveloped viruses—that include influenza virus, HIV, severe acute respiratory syndrome coronavirus, Ebola virus, yellow fever virus, and many others. The fusion of the viral with a cellular membrane is a key step in the life cycle of these viruses and allows the delivery of their genetic information into cells. This entry step is controlled by specific proteins at the viral surface that are primed to undergo dramatic structural changes and thus drive membrane fusion. An interference with this process can be a powerful means for inhibiting virus replication and fusion inhibitors have recently become a valuable addition to the armamentarium of anti-HIV treatments. In the present study, we identified an intermediate of the fusion pathway of flaviviruses, which comprise mosquito- and tick-transmitted viruses such as yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. This work has generated further insights into the mechanism of flavivirus membrane fusion and can thus provide new leads for the development of antiviral agents against these important human pathogens.

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    PLoS Pathogens
    Article . 2007
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    PLoS Pathogens
    Article . 2007 . Peer-reviewed
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    ProdInra
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      PLoS Pathogens
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      PLoS Pathogens
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      PLoS Pathogens
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    Authors: Huber, Anna; Hajdu, Dorottya; Bratschun-Khan, Doris; Gáspári, Zoltán; +10 Authors

    AbstractSmall, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact β-folded structure, comprising five β-strands connected by four solvent exposed and flexible loops and an “abcabc” disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.

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    Scientific Reports
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    Scientific Reports
    Article . 2018
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    Scientific Reports; OpenAPC Global Initiative
    Article . Conference object . 2018 . Peer-reviewed
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      Scientific Reports; OpenAPC Global Initiative
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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: Camille Aubry; Sinéad C. Corr; Sebastian Wienerroither; Céline Goulard; +6 Authors

    PUBLISHED Synthesis of interferon-? (IFN-?) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-? synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-? production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ?pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-? gene, requiring TLR2 and bacterial internalization. Induction of IFN-? was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-? gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-? gene expression. Work in PC's laboratory received financial support from Institut Pasteur (http://www.pasteur.fr), Inserm (http://www.inserm.fr), INRA (http://www.inra.fr), ERC (Advanced Grant 233348, http://erc.europa.eu/), Fondation Pasteur-Weizmann and Fondation le Roch Les Mousquetaires (http://www.fondationleroch-lesmousquetai?res.org/). PC is an international research scholar of the Howard Hughes Medical Institute (http://www.hhmi.org/). CA is a doctoral fellow of the Ministere de l'Enseignement Superieur et de la Recherche. Work in LO's laboratory was supported by Science Foundation Ireland (http://www.sfi.ie/) and the Irish Research Council for Science, Engineering and Technology (RS/2005/190, http://www.ircset.ie/). Work in TD's laboratory was funded by the Austrian Research Foundation (grants SFB-28 and P20522-B05, http://www.fwf.ac.at). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    PLoS ONE
    Article . 2012
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    Authors: Burger, Pamela Anna; Ciani, Elena; Faye, Bernard;

    SummaryOld World camels have served humans in cross‐continental caravans, transporting people and goods, connecting different cultures and providing milk, meat, wool and draught since their domestication around 3000–6000 years ago. In a world of modern transport and fast connectivity, these beasts of burden seem to be out‐dated. However, a growing demand for sustainable milk and meat production, especially in countries affected by climate change and increasing desertification, brings dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus) back onstage and into the focus of animal breeders and scientists. In this review on the molecular genetics of these economically important species we give an overview about the evolutionary history, domestication and dispersal of Old World camels, whereas highlighting the need for conservation of wild two‐humped camels (Camelus ferus) as an evolutionarily unique and highly endangered species. We provide cutting‐edge information on the current molecular resources and on‐going sequencing projects. We cannot emphasise enough the importance of balancing the need for improving camel production traits with maintaining the genetic diversity in two domestic species with specific physiological adaptation to a desert environment.

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    Animal Genetics
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    Animal Genetics; OpenAPC Global Initiative
    Article . Conference object . 2019 . Peer-reviewed
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      Animal Genetics
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      Animal Genetics; OpenAPC Global Initiative
      Article . Conference object . 2019 . Peer-reviewed
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    Authors: Mélanie Bourgin; Lisa Derosa; Carolina Alves Costa Silva; Anne-Gaëlle Goubet; +12 Authors

    International audience; Cancer patients are particularly susceptible to the development of severe Covid-19, prompting us to investigate the serum metabolome of 204 cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive tryptophan/kynurenine metabolite anthranilic acid correlates with poor prognosis in non-cancer patients. In cancer patients, we observed an elevation of anthranilic acid at baseline (without Covid-19 diagnosis) and no further increase with mild or severe Covid-19. We found that, in cancer patients, Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory cytokines. Most importantly, we observed that the levels of acetylated polyamines (in particular N1-acetylspermidine, N1,N8-diacetylspermidine and N1,N12-diacetylspermine), alone or in aggregate, were elevated in severe Covid-19 cancer patients requiring hospitalization as compared to uninfected cancer patients or cancer patients with mild Covid-19. N1-acetylspermidine and N1,N8-diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated polyamines increase in the serum from patients with cancer, cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated polyamines are associated with severe Covid-19, both in the general population and in patients with malignant disease. Severe Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of spermine/spermidine N1-acetyl transferase-1 (SAT1), which catalyzes the first step of polyamine catabolism.

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    Authors: Carmona-Gutierrez, Didac; Bauer, Maria,; Zimmermann, Andreas; Kainz, Katharina; +3 Authors

    International audience; Autophagy is a catabolic pathway with multifaceted roles in cellular homeostasis. This process is also involved in the antiviral response at multiple levels, including the direct elimination of intruding viruses (virophagy), the presentation of viral antigens, the fitness of immune cells, and the inhibition of excessive inflammatory reactions. In line with its central role in immunity, viruses have evolved mechanisms to interfere with or to evade the autophagic process, and in some cases, even to harness autophagy or constituents of the autophagic machinery for their replication. Given the devastating consequences of the current COVID-19 pandemic, the question arises whether manipulating autophagy might be an expedient approach to fight the novel coronavirus SARS-CoV-2. In this piece, we provide a short overview of the evidence linking autophagy to coronaviruses and discuss whether such links may provide actionable targets for therapeutic interventions.

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    Microbial Cell
    Article . 2020 . Peer-reviewed
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    Microbial Cell
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    Microbial Cell
    Article . 2020
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      Microbial Cell
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      Microbial Cell
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      Microbial Cell
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    Authors: Jaber-Lopez, Tarek; Blanco, Esther; Baier, Alexandra; Holzmeister, Felix; +1 Authors

    Abstract Think tanks and political leaders have raised concerns about the implications that the Covid-19 response and reconstruction might have on other social objectives that were setting the international agenda before the Covid-19 pandemic. We present evidence for eight consecutive weeks during April–May 2020 for Austria, testing the extent to which Covid-19 concerns substitute other social concerns such as the climate crisis or the protection of vulnerable sectors of the society. We measure behavior in a simple donation task where participants receive €3 that they can distribute between themselves and a list of charitable organizations, which vary between treatments. We consider initially a list of eight charities, including a broad set of social concerns. Results show that introducing the WHO Covid-19 Solidarity Response Fund significantly reduces the sum of donations to the original eight charities. This derives from two effects: First, introducing the Covid-19 Solidarity Response Fund does not significantly change aggregate donations. Second, results point to a high support to the WHO Covid-19 Fund. Overall, our results indicate that donations to diverse social concerns are partially substituted by donations to the Covid-19 fund; yet, this substitution does not fully replace all other social concerns. Results are robust to a 10-fold increase in endowment, with decisions made over €30.

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    Ecological Economics
    Article . 2022 . Peer-reviewed
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    Authors: Stiasny, Karin; Kössl, Christian; Lepault, Jean; Rey, Félix A.; +1 Authors

    Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E) mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion. Author Summary The fusion of cellular lipid membranes is an essential process in all forms of life. Such membranes are also part of a specific structural class of viruses—so-called enveloped viruses—that include influenza virus, HIV, severe acute respiratory syndrome coronavirus, Ebola virus, yellow fever virus, and many others. The fusion of the viral with a cellular membrane is a key step in the life cycle of these viruses and allows the delivery of their genetic information into cells. This entry step is controlled by specific proteins at the viral surface that are primed to undergo dramatic structural changes and thus drive membrane fusion. An interference with this process can be a powerful means for inhibiting virus replication and fusion inhibitors have recently become a valuable addition to the armamentarium of anti-HIV treatments. In the present study, we identified an intermediate of the fusion pathway of flaviviruses, which comprise mosquito- and tick-transmitted viruses such as yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. This work has generated further insights into the mechanism of flavivirus membrane fusion and can thus provide new leads for the development of antiviral agents against these important human pathogens.

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    PLoS Pathogens
    Article . 2007
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    PLoS Pathogens
    Article . 2007 . Peer-reviewed
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    ProdInra
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      PLoS Pathogens
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    Authors: Huber, Anna; Hajdu, Dorottya; Bratschun-Khan, Doris; Gáspári, Zoltán; +10 Authors

    AbstractSmall, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact β-folded structure, comprising five β-strands connected by four solvent exposed and flexible loops and an “abcabc” disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.

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