29 research outputs found

    Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

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    © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs-/- mice show enhanced susceptibility to A. fumigatus infection. Murine and human SAP bound conidia, activate the complement cascade and enhance phagocytosis by neutrophils. Apcs-/- mice are defective in vivo in terms of recruitment of neutrophils and phagocytosis in the lungs. Opsonic activity of SAP is dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protects hosts against A. fumigatus infection and death. In the context of a study of hematopoietic stem-cell transplantation, genetic variation in the human APCS gene is associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus.The contribution of the European Commission (ERC project PHII-669415; FP7 project 281608 TIMER; ESA/ITN, H2020-MSCA-ITN-2015-676129), Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) (project FIRB RBAP11H2R9), Associazione Italiana Ricerca sul Cancro (AIRC IG-19014 and IG-21714, AIRC 5 × 1000 −9962 and −21147), the Italian Ministry of Health, the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023), the Fundação para a Ciência e Tecnologia (FCT) (UIDB/50026/2020, UIDP/50026/2020, PTDC/SAU-SER/29635/2017, PTDC/MED-GEN/28778/2017, CEECIND/04058/2018 and CEECIND/03628/2017), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 847507 and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003 is gratefully acknowledged.info:eu-repo/semantics/publishedVersio

    Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

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    OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

    Multi-Robot Planning Under Uncertain Travel Times and Safety Constraints

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    We present a novel modelling and planning approach for multi-robot systems under uncertain travel times. The approach uses generalised stochastic Petri nets (GSPNs) to model desired team behaviour, and allows to specify safety constraints and rewards. The GSPN is interpreted as a Markov decision process (MDP) for which we can generate policies that optimise the requirements. This representation is more compact than the equivalent multi-agent MDP, allowing us to scale better. Furthermore, it naturally allows for asynchronous execution of the generated policies across the robots, yielding smoother team behaviour. We also describe how the integration of the GSPN with a lower-level team controller allows for accurate expectations on team performance. We evaluate our approach on an industrial scenario, showing that it outperforms hand-crafted policies used in current practice

    Lipid Droplets as Potential Antiviral Targets for Flaviviruses

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    Lipid droplets (LDs) are intracellular sites for neutral lipid storagecritical for lipid metabolism and energy homeostasis. Structurally, LDshave a rich lipid content but they also contain several functionally diversetypes of proteins, including already described pro and antiviral relevantfactors. New roles for LDs in immunity have been uncovered, withevidence that they act as assembly and replication platforms for specificviruses and as reservoirs for proteins that counteract intracellularpathogens. LDs might also have potential implications for mechanisms ofcell proliferation and differentiation, affecting viral replication. Cellpathological conditions have been noticed to share an altered lipogenesisphenotype. However, the mechanisms that regulate LDs formation orconsumption and how their function impacts the cellular biology remainunknown. These evidences led us to investigate the effect of the alterationof LDs abundance during the replication of mosquito-transmittedflaviviruses. Our in vitro studies show that there is a decreased LDscontent in dengue, Zika and yellow fever infected cells, demonstratingthat these structures might be essential for diverse RNA virus life cycleand could be considered a novel antiviral target.Fil: Vázquez, Cecilia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Giovannoni, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Irene Bosch. Massachusetts Institute of Technology; Estados UnidosFil: de Oliveira Mota, Mânlio Tasso. Faculty of Medicine of São José do Rio Preto; BrasilFil: Lacerda Nogueira, Mauricio. Faculty of Medicine of São José do Rio Preto; BrasilFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin
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