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Objectives Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID‐19). We isolated neutrophils from the blood of COVID‐19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. Methods Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co‐culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) allowed us to investigate viral replication in neutrophils. Results Upon ICU admission, patients displayed high plasma concentrations of granulocyte–colony‐stimulating factor (G‐CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10−, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non‐metalloproteinase‐derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP‐1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID‐19 neutrophils were hyper‐responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS‐CoV‐2 failed to replicate inside human neutrophils. Conclusion Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID‐19 patients, and supports the concept of an increased neutrophil activation state in the circulation., In this study, we found that patients suffering from severe COVID‐19 presented with immature, activated blood neutrophils and were characterized by elevated plasma levels of G‐CSF and CXCL8 that disappeared towards ICU discharge. Elevated neutrophil‐derived proteases in plasma of ICU patients were associated with increased non‐metalloproteinase‐derived gelatinolytic activity but decreased total MMP proteolytic activity. SARS‐CoV‐2 failed to replicate inside human neutrophils, suggesting that changes observed in neutrophils from patients with COVID‐19 are indirect consequences of SARS‐CoV‐2 infection in vivo.

Made available in DSpace on 2020-12-12T02:25:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19. Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death. Laboratory of Immunometabolism Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas Department of Biochemistry and Tissue Biology Institute of Biology University of Campinas Department of Genetics at Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto Department of Clinical and Toxicological analyses School of Pharmaceutical Sciences University of São Paulo Brazilian Biosciences National Laboratory (LNBio), Campinas Department of Animal Biology Institute of Biology University of Campinas, Campinas Department of Internal Medicine School of Medical Sciences University of Campinas, Campinas Department of Clinical Medicine School of Medical Sciences University of Campinas, Campinas Hematology and Hemotherapy Center University of Campinas, Campinas Obesity and Comorbidities Research Center (OCRC) University of Campinas Experimental Medicine Research Cluster (EMRC) University of Campinas Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu D'Or Institute for Research and Education (IDOR) Instituto Nacional de Biomarcadores em Neuropsiquiatria Conselho Nacional de Desenvolvimento Científico e Tecnológico Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu FAPESP: 20/04579-7 FAPESP: 2015/15626-8 FAPESP: 2016/18031-8 FAPESP: 2016/23328-0 FAPESP: 2017/01184-9 FAPESP: 2018/22505-0 FAPESP: 2019/00098-7 FAPESP: 2019/06372-3 FAPESP: 2020/04522-5 FAPESP: 2020/04558-0 FAPESP: 2020/04583-4 FAPESP: 2020/04746-0 FAPESP: 2020/04919-2 Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas: 2274/20

Este texto aborda o trabalho de mascaramento do ator e a sua relacao entre mascara, jogo do ator e a cultura urbana local, discutindo a reverberacao de suas potencialidades cenicas junto ao movimento de urbanizacao da cidade de Porto Alegre. A expressao mascaramento caracteriza-se por ser o ato ou efeito de mascarar-se, e se deriva do termo mascara , que por sua vez tem origem na palavra italiana maschera, que denota ornamento de disfarce. Ela e aqui utilizada para designar o trabalho do ator em cena como um ato de passagem de sua identidade cotidiana a uma outra, expressiva e ficcional, utilizando-se de principios tecnicos de movimentos e de acoes fisicas do ator.

COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes/macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor- 1α (HIF - 1α) and consequently promotes glycolysis. HIF- 1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1 ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

Mayaro virus (MAYV) belongs to the Alphavirus genus along with other important viruses such as Chikungunya virus (CHIKV). The chronic disease caused by MAYV is described by a highly incapacitating joint pain which may endure for several weeks or months in at least 50% of the symptomatic patients. Recently, reports of sporadic outbreaks in humans has increased, however, the dynamic of the Mayaro infection is not completely understood and there is still no treatment or vaccine available. Herein, our goal was to develop an animal immunocompromised model ideal to understand the immunologic dynamic of the disease and perform antiviral tests.

Encontrar o jogo. Jogar com o encontro. Eis o motivo principal deste trabalho, que se desenvolve a partir de uma perspectiva artística, através de uma abordagem prática baseada em estudos teatrais que envolvem o jogo do ator com a máscara na rua. Por meio das experiências artísticas e pedagógicas com a Cia Familie Flöz, Irion Nolasco, Liane Venturella e Tiche Vianna, e através das práticas do grupo Máscara EnCena, este trabalho busca relacionar elementos que direcionam a expressividade do corpo, como o foco, interesse, ação, reação, triangulação, estados de leveza, peso, retração e expansão, assim como as qualidades físico-energéticas do buoyancy, potency e radiancy propostas por Arthur Lessac, afim de encontrar uma identidade entre corpo e máscara em relação criativa e interativa com a rua. A partir de práticas do processo de mascaramento do ator, ou seja, da transposição de qualidades físicas que condicionam ao corpo outras possibilidades expressivas, a presente pesquisa debruça-se sobre o jogo do ator com a máscara inteira expressiva em contato com a rua e a cultura urbana da cidade de Porto Alegre. Desse modo, o trabalho propõe a articulação entre tais princípios e a expressividade criativa do ator em jogo na rua, servindo-se de procedimentos e experimentações com a máscara. Encounter the performance. Play with the encounter. This is the main objective of this research, which develops from an artistic perspective, through a practical approach based on theatrical studies that involve the actor's performance with the mask on the streets. This research seeks to relate elements which direct the expressiveness of the body, such as focus, interest, action , reaction, triangulation, states of lightness, weight, retraction and expansion, as well as the physical-energetic qualities of buoyancy, potency and radiancy proposed by Arthur Lessac, through artistic and pedagogical experiences with Cia Familie Flöz, Irion Nolasco, Liane Venturella and Tiche Vianna, and through practices of Mascara EnCena group, in order to find an identity between body and mask in a creative and interactive relation with the streets. Starting from practices such as the masking process of the actor, which is, the transposition of physical qualities that condition the body to other expressive possibilities, this research looks at the actor's performance with the expressive mask as a whole, having contact with the streets and the urban culture in the city of Porto Alegre. Therefore, the research proposes articulation between such principles and the creative expressiveness of the actor in performance on the street, using procedures and experimentations with the mask.