A novel role for EXP2 in invasion by Plasmodium sporozoites

Plasmodium parasites, the causative agents of malaria, possess a translocon that exports parasite proteins into the infected erythrocyte, beyond the confines of the parasite. The parasite pore-forming protein Exported Protein 2 (EXP2) is a component of this translocon and the pore through which proteins are exported. Although EXP2, and other translocon components, are also expressed during the mosquito and liver stages of infection, their function remains unexplored. To study the function of EXP2 during the liver stage of infection, we used a genetically engineered Plasmodium berghei parasite line, generated by our collaborators. In this parasite line, the EXP2 gene is silenced during the mosquito stage, as the 3’ untranslated region of the EXP2 gene is excised, generating EXP2 knock-out sporozoites. The sporozoite is the mosquito transmissible form of the parasite, that when deposited in the mammalian host, infects the liver, giving rise to the pre-erythrocytic stage of Plasmodium infection. Using this transgenic parasite line, we observed that invasion of the hepatocyte by EXP2 conditional knock-out parasites is impaired, both in C57Bl/6J mice and in the hepatoma cell line HepG2, suggesting that invasion is dependent on EXP2. Using a combination of fluorescence and electron microscopy techniques, we show that EXP2 is present in the hepatocyte-infectious sporozoite in vesicles, in the apical end of the parasite. These vesicles are important for the invasion process, as they are discharged by the sporozoite and contain proteins important for hepatocyte adhesion and entry in the host cell. Stimulating sporozoites with conditions that mimic the host cell milieu, we observed that EXP2 relocates to the surface of the mosquito-transmitted sporozoite and that it is secreted by the sporozoite. We also observed that invasion defect of the EXP2 conditional knock-out parasites can be rescued by the exogenous administration of recombinant EXP2 or recombinant α-hemolysin, another pore-forming protein, suggesting that the function of EXP2 is through its pore-forming ability on the membrane of the hepatocyte. Invasion of cells via pores has been documented for a variety of intracellular pathogens, like Trypanossoma cruzi, Listeria monocytogenes and adenovirus. Importantly, the pore does not allow the parasite to cross the membrane, rather it induces changes in the host cell that make it endocytose the wounded region of the membrane. We observed that recombinant EXP2 can recapitulate the major hallmarks of the membrane repair pathway. On one hand, treating cells with recombinant EXP2 leads to influx of calcium to HepG2 cells. Moreover, invasion of Plasmodium berghei sporozoites is dependent of acid Sphingomyelinase and finally, the invasion defect of the EXP2 conditional knock-out sporozoites can be rescued by exogenously adding acid sphingomyelinase. This suggest that indeed EXP2 induces hepatocyte membrane repair, which plays a key role in parasite invasion. Overall, while our data show that Plasmodium parasites uses EXP2 for divergent functions in its life cycle, it also highlights the convergent evolution of different intracellular pathogens, which have developed similar strategies to take advantage of cellular responses to membrane damage, hitchhiking their way into the host cell

The nutrient games - Plasmodium metabolism during hepatic development

© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Malaria is a febrile illness caused by species of the protozoan parasite Plasmodium and is characterized by recursive infections of erythrocytes, leading to clinical symptoms and pathology. In mammals, Plasmodium parasites undergo a compulsory intrahepatic development stage before infecting erythrocytes. Liver-stage parasites have a metabolic configuration to facilitate the replication of several thousand daughter parasites. Their metabolism is of interest to identify cellular pathways essential for liver infection, to kill the parasite before onset of the disease. In this review, we summarize the current knowledge on nutrient acquisition and biosynthesis by liver-stage parasites mostly generated in murine malaria models, gaps in knowledge, and challenges to create a holistic view of the development and deficiencies in this field.This work was also financed by la Caixa Foundation (HR17/52150010) to M.M.M.info:eu-repo/semantics/publishedVersio

O desfecho clinico do paciente obeso submetido a cirurgia / The clinical outcome of the obese patient undergoing

A obesidade se trata de uma doença multifatorial e de caráter crônico, necessitando ser precocemente diagnosticada e tratada. O tratamento do excesso de peso corporal têm a finalidade de evitar exacerbações da doença e as comorbidades com ela associadas. O seguinte artigo objetivou por meio da literatura científica abordar e descrever o quadro clínico do paciente obeso e as opções cirúrgicas e seu prognóstico. O estudo em questão é uma revisão de literatura do tipo narrativa, fundamentada nas plataformas online do SciELo, Pubmed, Google Acadêmico, Brazilian Jornal of Health Review e LILACS. Desta pesquisa foram analisados 50 artigos, nos idiomas português, inglês e espanhol. Foram selecionados 20 estudos por estarem atuais, baseados em evidências e com linguagem clara e direta, descartando-se os demais sem relevância para a temática proposta. Na literatura existem muitas informações. Algumas perspectivas mais restritas classificam as causas da obesidade apenas entre o desequilíbrio entre a ingesta calórica e o gasto metabólico. Ademais, estudos mais atuais abordam a questão em sua perspectiva mais realista, ou seja, sua base multifatorial a qual incluem fatores genéticos, neurológicos, metabólicos e endócrinos, associados a um estilo de vida sedentário e a uma alimentação hipercalórica. O diagnóstico clínico se baseia em métodos simples e de fácil aplicabilidade, e a terapêutica se fundamenta em reeducação alimentar e a inclusão de atividades físicas. No advém, alguns pacientes são resistentes a esses meios e urgem ser submetidos a opção cirúrgica. Atualmente, a cirurgia bariátrica é a opção e esta conta com diversas técnicas promissoras e eficazes no combate ao excesso de peso e suas implicações adjacentes. E está possui benefícios e complicações que consoante o perfil clínico do paciente e o acompanhamento multidisciplinar pode resultar em bom prognóstico

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazonia Sustentavel, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.Keywords: Social–ecological systems, Tropical forests, Land use, Interdisciplinary research, Sustainability, Trade-off

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Chemotaxonomic significance of 5-deoxyproanthocyanidins in Stryphnodendron species

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

70º Aniversario de la declaración universal de derechos humanos. La protección internacional de los Derechos Humanos en cuestión

Segundo volúmen de la Colección Perspectivas Iberoamericanas sobre la justicia. La Declaración Universal de los Derechos Humanos de las Naciones Unidas cumple, el 10 de diciembre de 2018, setenta años. La simbólica fecha obliga a los investigadores en derechos humanos a reflexionar críticamente sobre los avances y límites de un complejo sistema de normas y, sobre todo, de valores culturales sustentados en la matriz liberal occidental. Desde entonces, ha habido indiscutibles avances institucionales y normativos, como la creación del Consejo de Derechos Humanos, varios pactos y declaraciones complementarias, órganos específicos, tribunales internacionales, jurisprudencia, constituciones estatales, una infinidad de instituciones basadas en esta “ética mínima universal” que, contradictoriamente, no logró evitar un conjunto de catástrofes humanitarias y de vulneración de derechos. La primera década del siglo XX trae un reflejo limitante al consenso de la posguerra, pues la agresividad de los Estados hegemónicos, en alianza con intereses privados transnacionales, pone en jaque la capacidad del sistema protector frente a guerras humanitarias e internacionales. tratados económicos de nueva generación aquellos que excluyen por completo a la democracia del proceso de negociación.A Declaração Universal dos Direitos Humanos das Nações Unidas completa, em 10 de diciembre de 2018, setenta años. A data simbólica exige dos pesquisadores em direitos humanos uma reflexão crítica a respeito dos avanços y dos limites de um sistema complexo de normas e, principalmente, de valores culturales apoiados na matriz liberal ocidental. De lá para cá, houve indiscutível avanço institucional e normativo, do qual é exemplo a criação do Conselho de Direitos Humanos, diversos pactos e declarações complementarios, órgão específicos, tribunais internacionais, jurisprudência, constituições dos States, uma infinidade de instituições pautadas nesse “mínimo ético universal” que, contraditoriamente, não conseguiu evitar um conjunto de catástrofes humanitárias e de violação de direitos. A primeira década do século XX traz uma reflexão limite para o consenso do pós-guerra, pois a agressividade dos States hegemônicos, em aliança com interesses private transnacionais, põe em check a capacidade do sistema protectivo diante das guerras humanitárias e dos tratados internacionais econômicos de nueva generación aqueles que excluem completamente a democracia do processo negociador

ATLANTIC MAMMAL TRAITS: a data set of morphological traits of mammals in the Atlantic Forest of South America

Univ Estadual Paulista, UNESP, Dept Ecol, Inst Biociencias, BR-13506900 Rio Claro, SP, BrazilUniv Fed Santa Catarina, Ctr Ciencias Biol, Dept Ecol & Zool, Florianopolis, SC, Brazil|Caipora Cooperat, Florianopolis, SC, BrazilUniv Estadual Santa Cruz, Programa Posgrad Ecol & Conservac Biodiversidade, Lab Ecol Aplicada Conservacao, Ilheus, BA, BrazilUniv Estadual Santa Cruz, CMARF, Ilheus, BA, BrazilUniv Brasilia, Dept Ecol, Inst Ciencias Biol, Lab Ecol Vertebrados, Brasilia, DF, BrazilUniv Fed Santa Maria, Dept Ecol & Evolut, Santa Maria, RS, BrazilUniv Sao Paulo, Inst Biociencias, Dept Zool, Sao Paulo, SP, BrazilUniv Fed Espirito Santo, Ctr Ciencias Humanas & Nat, Dept Ciencias Biol, Vitoria, ES, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Belo Horizonte, MG, BrazilUniv Fed Mato Grosso de Sul, Inst Biociencias, Campo Grande, MS, BrazilUniv Fed Parana, Dept Zool, Curitiba, Parana, BrazilUniv Fed Parana, Programa Posgrad Ecol & Conservcao, Curitiba, Parana, BrazilUniv Estado Rio de Janeiro, Dept Ecol, Rio De Janeiro, RJ, BrazilUniv Estadual Paulista, UNESP, Inst Biociencias, Dept Zool, Rio Claro, SP, BrazilUniv Extremo Sul Catarinense, Programa Posgrad Ciencias Ambientais, Criciuma, SC, BrazilUniv Sao Paulo, ESALQ, Dept Ciencias Biol, Piracicaba, SP, BrazilUniv Nacl Misiones, CONICET, Inst Biol Subtrop, Puerto Iguazu, Misiones, ArgentinaAsociac Civil Ctr Invest Bosque Atlantico, Puerto Iguazu, Misiones, ArgentinaFIOCRUZ Amazonas, Inst Leonidas & Maria Deane, Manaus, Amazonas, BrazilUniv Estadual Paulista, UNESP, Dept Zootecnia, Jaboticabal, SP, BrazilField Museum Nat Hist, Integrated Res Ctr, Chicago, IL 60605 USAUniv Fed Pernambuco, Ctr Biociencias, Dept Zool, Lab Ciencia Aplicada Conservacao Biodiversidade, Recife, PE, BrazilInst Chico Mendes Conservacao Biodiversidade, Ctr Nacl Pesquisa & Conservacao Mamiferos Carnivo, Sao Paulo, BrazilUniv Vale Rio dos Sinos, Sao Leopoldo, RS, BrazilUniv Reg Cariri, Dept Biol, Lab Ecol Mamiferos, Crato, CE, BrazilUniv Fed Rio de Janeiro, Dept Ecol, Lab Vertebrados, Rio De Janeiro, RJ, BrazilUniv Federal Mato Grosso do Sul, Programa Posgrad Ecol & Conservacao, Campo Grande, MS, BrazilIPE, Nazare Paulista, SP, BrazilUniv Fed Minas Gerais, Programa Posgrad Zool, Belo Horizonte, MG, BrazilUniv Estado Minas Gerais, Dept Ciencias Biol, Ibirite, MG, BrazilPREA, Programa Educ Ambiental, Juiz De Fora, MG, BrazilChinese Acad Sci, Inst Zool, Key Lab Zool Systemat and Evolut, Beijing, Peoples R ChinaMinist Salud Nacion, Inst Nacl Med Trop INMeT, Puerto Iguazu, Misiones, ArgentinaUniv Fed Vicosa, Dept Engn Florestal, Vicosa, MG, BrazilUniv Fed Goias, Inst Biociencias, Jatai, Go, BrazilInst Chico Mendes Conservacao Biodiversidade ICMB, Ctr Nacl Pesquisa & Conservacao Primatas Brasilei, Joao Pessoa, PB, BrazilCtr Rescate Fauna Silvestre Guira Oga, Puerto Iguazu, ArgentinaFdn Hist Nat Felix de Azara, Buenos Aires, ArgentinaProjeto Carnivoros Iguacu, Foz Do Iguacu, PR, BrazilUniv Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet Jaboticabal, Jaboticabal, SP, BrazilUniv Fed Integracao Latinoamer, Inst Latinoamer Ciencias Vida & Nat, Foz Do Iguacu, PR, BrazilUniv Fed Sao Paulo, Dept Ciencias Ambientais, Diadema, SP, BrazilUniv Fed Paraiba, Dept Sistemat & Ecol, Lab Mamiferos, Joao Pessoa, Paraiba, BrazilIUCN Peccary Specialist Grp, Campo Grande, MS, BrazilWWF Brazil, Campo Grande, MS, BrazilChicago State Univ, Dept Biol Sci, Chicago, IL USAUniv Fed Rio de Janeiro, Nucleo Ecol & Desenvolvimento Socioambiental Maca, Macae, RJ, BrazilUniv Vila Velha, Programa Posgrad Ecol Ecossistemas, Vila Velha, ES, BrazilUniv Fed Rio de Janeiro, Museu Nacl, Dept Vertebrados, Rio De Janeiro, RJ, BrazilUniv Fed Bahia, Programa Posgrad Ecol, Salvador, BA, BrazilUniv Fed Paraiba, Dept Sistemat & Ecol, Programa Posgrad Ciencias Biol Zool, Lab Mamiferos, Joao Pessoa, Paraiba, BrazilUniv Fed Sao Paulo, Dept Ciencias Ambientais, Diadema, SP, BrazilWeb of Scienc