Modelos de interacção genética de dois genes em fenótipos

Em trabalhos anteriores foram propostos diversos modelos estatísticos para a penetrância de forma a inferir a interacção de dois genes dial´elicos na construção de fenótipos binários complexos: modelos de acção independente, modelos de inibição e modelos de número mínimo de alelos. Estes modelos baseiam-se numa decomposição da penetrância através da abordagem por penetrâncias alélicas, que permitiu a inclusão dos conceitos mendelianos de dominância e recessividade alélica na sua modelação. Pretende-se aqui dar a conhecer os avanços mais recentes na parte da modelação da interacção genética, apresentando uma nova decomposição da penetrância e uma nova formulação matemática da dominância e da recessividade. Aplicam-se ainda ferramentas bayesianas para o ajustamento dos modelos de interacção genética a dados experimentais com recurso ao método de amostragem de Gibbs. Toda a metodologia é exemplificada num conjunto de dados de um estudo da susceptibilidade da malária cerebral em ratinhos

Placental Malaria: From Infection to Malfunction

Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction.Fundação para a Ciência e Tecnologia

The multigenic structure of the MHC locus contributes to positive selection efficiency: A role for MHC class II gene-genespecific

This deposit is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.200535190The study of T cell positive selection in the thymus has long been focused on the specificity of the MHC-TCR interactions, making use of genetically manipulated mice that display TCR specificities or selecting peptides of limited diversity. However, little is known on the role of the MHC molecules irrespective of the peptide specificity and the implications of MHC multigenic structure in thymic positive selection have not been addressed. Here, we investigated the effect of MHC class II genetic configuration on the positive selection efficiency of naturally generated pre-selection repertoires in the mouse thymus. Analysis of positively selected thymocyte populations in MHC-congenic and -transgenic mice revealed that expression of I-E molecule in the thymic cortex increases positive selection efficiency of CD4 cells by approximately 50%.We show that increments in positive selection attributable to either the I-A and I-E genes are not due to increased MHC class II expression in the thymic cortex and are not affected by the number of MHC alleles. Collectively, our findings imply that MHC class II generestricted TCR specificities significantly contribute to positive selection efficiency, introducing the notion that multigenic structure of the MHC locus serves to increase selection of non-overlapping TCR repertoires

Studio report : DIGITÓPIA at casa da Musica

Today's increasing availability of free music software and musical content. Digitópia, a platform for collaborative music creation recently started at Casa da Música, Porto's main concert venue, addresses how these trends can affect generalized music creation and music software design, promote social inclusion, and lead to the emergence of multicultural communities of music makers/lovers. In this paper, we report on the musical activities conducted in the first months of existence of Digitópia, and highlight some developments for the future

Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death

This deposit is composed by the main article, and it hasn't any supplementary materials associated.Plasmodium infection during gestation may lead to severe clinical manifestations including abortion, stillbirth, intrauterine growth retardation, and low birth weight. Mechanisms underlying such poor pregnancy outcomes are still unclear. In the animal model of severe placental malaria (PM), in utero fetal death frequently occurs and mothers often succumb to infection before or immediately after delivery. Plasmodium berghei-infected erythrocytes (IEs) continuously accumulate in the placenta, where they are then phagocytosed by fetal-derived placental cells, namely trophoblasts. Inside the phagosomes, disruption of IEs leads to the release of non-hemoglobin bound heme, which is subsequently catabolized by heme oxygenase-1 into carbon monoxide, biliverdin, and labile iron. Fine-tuned regulatory mechanisms operate to maintain iron homeostasis, preventing the deleterious effect of iron-induced oxidative stress. Our preliminary results demonstrate that iron overload in trophoblasts of P. berghei-infected placenta is associated with fetal death. Placentas which supported normally developing embryos showed no iron accumulation within the trophoblasts. Placentas from dead fetuses showed massive iron accumulation, which was associated with parasitic burden. Here we present preliminary data suggesting that disruption of iron homeostasis in trophoblasts during the course of PM is a consequence of heme accumulation after intense IE engulfment. We propose that iron overload in placenta is a pathogenic component of PM, contributing to fetal death. The mechanism through which it operates still needs to be elucidated.FCT: Portugal (EXPL-IMI-IMU-0428/2013), SFRH/BPD/44256/2008, SFRH/BPD/44486/2008

Improved isolation of murine hepatocytes for in vitro malaria liver stage studies

<p>Abstract</p> <p>Background</p> <p>Primary hepatocyte cultures are a valuable tool for the understanding of cellular and molecular phenomena occurring during malaria liver stage. This paper describes an improved perfusion/dissociation procedure to isolate hepatocytes from mouse liver that is suitable for malaria studies and allows reproducible preparation of primary hepatocytes with consistent cell yields and controlled purity.</p> <p>Results</p> <p>This protocol is a detailed description of a technique to isolate and culture mouse hepatocytes and represents an improvement over previous descriptions of hepatocyte isolation for malaria studies, regarding three technical aspects: (1) dissociation reagents choice; (2) cell separation gradient and (3) cell purity control. Cell dissociation was optimized for a specific collagenase digestion media. The cell dissociation step was improved by using a three-layer discontinuous gradient. A cell purity check was introduced to monitor the expression of CD95 on hepatocytes using flow cytometry methods.</p> <p>Conclusion</p> <p>The procedure described allows reproducible recovery of one to three million hepatocytes per preparation with cell purity of about 90% as determined by FACS analysis. Completion of the protocol is usually achieved in about four hours per preparation and pooling is suggested for multiple preparations of larger number of cells.</p

A responsabilidade civil estatal por omissão ou falha no dever de fiscalizar : um estudo centrado na ocorrência de tragédias no direito brasileiro

Por meio do método dialético e da análise de entendimentos doutrinários, jurisprudenciais e das legislações nacionais, este trabalho busca demonstrar como o Estado poderá ser responsabilizado no âmbito civil por sua omissão ou falha no dever de fiscalizar em relação a tragédias. Para tanto, se faz um estudo sobre o porquê o Estado tem o dever de fiscalizar com base no poder de polícia e nos princípios da eficiência, precaução e prevenção. No segundo momento, é realizado um estudo sobre a evolução histórica da responsabilidade civil do Estado, posteriormente, entramos no tema da responsabilidade extracontratual do Estado por omissão e falha no dever de fiscalizar e tratamos da polêmica entre qual forma o Estado deverá responder, objetivamente ou subjetivamente. No terceiro momento é mostrado a importância do nexo causal para ocorrer a responsabilidade civil do Estado. Por fim, foi demonstrado quais as excludentes de responsabilidade civil são utilizadas pelo Estado e os entes que fazem o papel do Estado, a fim de romper o nexo causal e não precisar indenizar as vítimas de tragédias.Through the dialectical method and the exame of the doctrinal understanding, jurisprudence and national legislation, the main objective of this academic work is to demonstrate how the state may be held liable, in the scope of civil rights law, for its omission or failure to inspect in relation to tragic events. Initially, it studies why the state has the duty of inspection, based on state police power and the principles of efficiency, precaution and prevention. In a second moment, it studies the historical evolution of the state's civil liability, the state extra-contractual liability as result of omission or failure to inspect, and the controversial between how the state should respond, objectively or subjectively. In a third moment, it exposes the importance of the causal nexus for the civil liability of the state. As conclusion, the study demonstrates which civil liability exclusionary rules are used by the state and the entities that play the state role in order to break the causal nexus and not be required to indemnify the victims of tragic events

A Role for Trem-2

Funding: This work was funded with the support of Ferring innovation grant 2019 from Ferring Research Institute, Gilead Genese 2019 from Gilead Sciences Lda, “Fundação para a Ciência e Tecnologia” (PTDC/MEC447 MET/29314/2017) and iNOVA4Health (UIDB/Multi/04462/2020).Liver disease accounts for millions of deaths worldwide annually being a major cause of global morbidity. Hepatotoxic insults elicit a multilayered response involving tissue damage, inflammation, scar formation, and tissue regeneration. Liver cell populations act coordinately to maintain tissue homeostasis and providing a barrier to external aggressors. However, upon hepatic damage, this tight regulation is disrupted, leading to liver pathology which spans from simple steatosis to cirrhosis. Inflammation is a hallmark of liver pathology, where macrophages and endothelial cells are pivotal players in promoting and sustaining disease progression. Understanding the drivers and mediators of these interactions will provide valuable information on what may contribute to liver resilience against disease. Here, we summarize the current knowledge on the role of macrophages and liver sinusoidal endothelial cells (LSEC) in homeostasis and liver pathology. Moreover, we discuss the expanding body of evidence on cell-to-cell communication between these two cell compartments and present triggering receptor expressed on myeloid cells-2 (Trem-2) as a plausible mediator of this cellular interlink. This review consolidates relevant knowledge that might be useful to guide the pursue of successful therapeutic targets and pharmacological strategies for controlling liver pathogenesis.publishersversionpublishe

A RESPONSABILIDADE CIVIL DO ESTADO POR OMISSÃO (OU FALHA) NO DEVER DE FISCALIZAÇÃO EM RELAÇÃO A GRANDES TRAGÉDIAS

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Avaliação da qualidade do procedimento curativo em pacientes internados em um hospital universitário

This observational and sectional study analyzed the quality of the wound dressing procedure performed on hospitalized patients at a medical surgical unit of a University Hospital, based on their classification according to the degree of care dependency and activity performance phases. Using a check list, 168 wound dressings were observed between October and December 2005. Procedure quality was analyzed based on the Positivity Index (IP) and values >70% were considered satisfactory.For the preparation, the IP was 68%, 63%, 73% and 75% for patients with degrees I, II, III and IV, respectively; for execution, 70%, 69%, 71% and 75% and, for unit organization, it was >70% for all degrees. However, the items: validity time frame checking, respect for aseptic principles and maintenance of logical sequence of procedures were compromised. Rigorous execution of procedures allows for risk decrease and assures benefic results for patients, conferring quality to nursing actions.Estudio observacional y seccional analizó la calidad del procedimiento curativo, realizado en pacientes internados en una unidad medico-quirúrgica de un Hospital Universitario, de acuerdo con el grado de dependencia asistencial y las fases de realización de la actividad. Con la utilización de un instrumento tipo check list fueran observados 168 curativos, entre octubre y diciembre 2005. La cualidad de los procedimientos fue analizada basada en el Índice de Positividad (IP) y fueron considerados satisfactorios aquellos que alcanzaron valores >70%. En la preparación, el IP fue de 68%, 73% y 75% para pacientes en grados I, II, III y IV, respectivamente; en la ejecución, fueran de 70%, 69%, 71% y 75% y en la de organización de la unidad, en todos los grados fue >70%. Entre tanto, los ítems: conferencia del plazo de validez de los materiales, respeto a los principios de asepsia y manutención de la secuencia lógica muestrearon se comprometidos. La ejecución rigorosa de un procedimiento posibilita reducción de riesgos, asegura resultados benéficos a los pacientes y confiere calidad a las acciones de enfermería.Estudo observacional e seccional analisou a qualidade do procedimento curativo desenvolvido em pacientes internados em unidade médico-cirúrgica de um Hospital Universitário, segundo grau de dependência assistencial e fases de realização da atividade. Entre outubro e dezembro de 2005, utilizando instrumento tipo check list, foram observados 168 curativos. A qualidade do processo desenvolvido foi analisada com base no Índice de Positividade (IP). Foram considerados satisfatórios os procedimentos que alcançaram valores >70%. No preparo, o IP foi de 68%, 63%, 73% e 75% para pacientes em grau I, II, III e IV, respectivamente; na execução, de 70%, 69%, 71% e 75% e na de organização da unidade, em todos os graus foi >70%. Entretanto, os itens: conferência do prazo de validade dos materiais, respeito aos princípios de assepsia e manutenção da seqüência lógica mostraram-se comprometidos. A execução rigorosa de um procedimento reduz riscos e confere qualidade às ações de enfermagem