248 research outputs found

    Lipophosphoglycans from \u3cem\u3eLeishmania amazonensis\u3c/em\u3e Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection

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    The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of purified LPGs from both strains was investigated during in vitro interaction with peritoneal murine macrophages and CHO cells and in vivo infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-κB inhibitor p-IκBα, but were not able to translocate NF-κB. In vivo experiments with sand flies showed that both stains were able to sustain infection in L. migonei. A preliminary biochemical analysis indicates intraspecies variation in the LPG sugar moieties. However, they did not result in different activation profiles of the innate immune system. Also those polymorphisms did not affect infectivity to the sand fly

    role of female sex hormone receptors

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    Funding Information: Funding: This study was supported by grant IECT-FAPEMA-05796/18 and FAPEMA IECT 30/2018-IECT Saúde, by the Research Center of the Portuguese Oncology Institute of Porto (project no. PI86-CI-IPOP-66-2017); by European Investment Funds by FEDER/COMPETE/POCI—Operational Competitiveness and Internationalization Program, and national funds by FCT—Portuguese Foundation for Science and Technology under projects UID/AGR/04033/2020, UIDB/CVT/00772/2020 and by Base Funding-UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology, and Energy—LEPABE—funded by national funds through the FCT/MCTES (PID-DAC); Project 2SMART-engineered Smart materials for Smart citizens, with reference NORTE-01-0145-FEDER-000054, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Por-tugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.publishersversionpublishe

    Vulnerabilidade estrutural dos hospitais e cemitérios e crematórios da cidade de São Paulo à COVID-19

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    This is the first report by the COVID19 Observatory - Group: Contagion Networks analyzing mortality data from the city of São Paulo. In this report, we integrated mortality data for the city of São Paulo between 04/02/2020 and 04/28/2020, with information on the flow of victims between hospitals and cemeteries/crematoriums. We included in our analyzes both confirmed and suspected deaths from COVID-19. The main objectives of this report were: (1) to describe the structure of the flow of victims between locations and (2) to suggest changes in the current flow based on geographical distances in order to avoid a potential overload of the mortuary system. We suggest that the city of São Paulo should plan for a potential overload of the mortuary system (that is, the number of burials), based on the presented results. Thus, our results reinforce the need to adopt specific planning for the management of the extraordinary number of victims of this pandemic. Our predictions are based on the structural analysis of the COVID-19 victim flow network, which shows several hotspots with high vulnerability to system overload. These hotspots concentrate with either the greatest number of deaths (hospital) or of burials (cemetery or crematorium), and therefore have high potential to become overwhelmed by receiving many bodies due to the increase in victims of the pandemic. We recommend special attention to be given to localities on the east side of São Paulo, which has both the most vulnerable hospitals in the city, and also houses cemeteries and crematoriums that have a central role in the network and / or are vulnerable. Based on our optimization analysis, we suggest logistical changes in the current flow of bodies from hospitals to cemeteries/crematoriums so as not to overload the funeral system and minimize transportation costs. In this sense, our results are potentially useful for improving the operational planning of the Municipality of São Paulo, ratifying or rectifying actions underway at the municipal level.Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio analisando os dados de óbitos da cidade de São Paulo. Neste relatório, integramos os dados de óbitos da cidade de São Paulo entre os dias 02/04/2020 e 28/04/2020 com informações sobre o fluxo de vítimas entre os hospitais e os cemitérios e crematórios da cidade de São Paulo. Incluímos em nossas análises óbitos confirmados e óbitos suspeitos de COVID-19. Os principais objetivos deste relatório são: (1) descrever a estrutura do fluxo de vítimas entre localidades e (2) sugerir mudanças no fluxo com base em distâncias geográficas de maneira a evitar uma potencial sobrecarga do sistema funerário. Sugere-se à prefeitura da cidade de São Paulo que seja realizado um planejamento para uma potencial sobrecarga do sistema funerário (isto é, número de sepultamentos) da cidade de São Paulo com base nos resultados apresentados. Desta forma, nossos resultados reforçam a necessidade de ser adotado planejamento específico para a gestão dos casos extraordinários visualizados no contexto da pandemia. Esta previsão está baseada na análise estrutural da rede de fluxos de vítimas da COVID-19, que indica a concentração de vários locais com alta vulnerabilidade à sobrecarga do sistema. Tais locais concentram a maior quantidade de óbitos (hospitais) ou a maior concentração de sepultamentos (cemitérios ou crematórios) e tem portanto alto potencial de tornarem-se sobrecarregados por receberem muitos corpos devido ao aumento de vítimas da pandemia. Recomenda-se especial atenção à localidades da zona leste de São Paulo, que apresenta os hospitais mais vulneráveis da cidade e abriga cemitérios e crematórios que possuem papel central na rede e/ou encontram-se vulneráveis. Com base em nossa análise de otimização, sugerimos mudanças logísticas no atual fluxo de corpos de hospitais para cemitérios/crematórios de modo a não sobrecarregar o sistema funerário e minimizar os custos de transporte. Neste sentido, nossos resultados são potencialmente úteis ao aperfeiçoamento do planejamento operacional da Prefeitura Municipal de São Paulo, ratificando ou retificando ações em curso no âmbito municipal

    Vulnerabilidade das microrregiões da Região Sul do Brasil à pandemia do novo coronavírus (SARS-CoV-2)

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    This is the first report of the ‘Observatório COVID191 - Grupo: Redes de Contágio – Laboratório de Estudos de Defesa’ for the South region of Brazil. We have combined data of confirmed cases of the new coronavirus (SARS-CoV-2) for the South available up to 17/04/2020, with structural analyses of road networks, from within and between states, to estimate the vulnerability and potential influence of the South micro-regions to propagate the disease.Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio – Laboratório de Estudos de Defesa para a região Sul do Brasil. Combinamos dados de casos confirmados do novo coronavírus (SARS-CoV-2) para o Sul, disponíveis até o dia 17/04/2020, com análises estruturais da rede de rotas rodoviárias intra e interestaduais para estimarmos a vulnerabilidade e potencial influência das microrregiões sulinas na propagação da doença

    Estimating the global conservation status of more than 15,000 Amazonian tree species

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    Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict thatmost of the world’s >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century
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