MOTHER-TO-CHILD TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION

Introdução: A Infeção pelo Vírus da Imunodeficiência Humana do tipo 1 (VIH1) na criança ocorre quase exclusivamente por transmissão mãe-filho (TMF). Sem profilaxia ocorrem taxas de transmissão de 15-25%, diminuindo para <2% quando são adotadas medidas adequadas. Objetivo: Avaliar a TMF da Infeção VIH numa maternidade. Material e Métodos: Estudo retrospetivo, com consulta do processo clínico, de crianças de mães com Infeção VIH1, nascidas na Maternidade Júlio Dinis de Janeiro de 2006 a Dezembro de 2011. Definida não Infeção se 2 testes virológicos negativos (um após os 4 meses) e ausência de clínica. Analise estatística – programa Epi-InfoR v.3.5.1 (Teste Fisher, p <0,05). Resultados: Nasceram 77 crianças com risco de transmissão VIH1, 45 do sexo masculino (58.4%) e 15 (19.5%) prematuros. Diagnostico de Infeção materna ocorreu na gestação em 24 (31.6%) e no parto numa (1.3%). Sete (9.2%) Não efetuaram terapêutica anti retrovirica (TARV) na gravidez e 9 (12.3%) apresentavam carga vírica >1.000 copias no parto. Nasceram por parto eutocico 4 (5.2%) e 10 (13%) tiveram rotura membranas (RM) ≥4h. Nenhum efetuou leite materno e todos fizeram profilaxia no periodo neonatal; 17 (22.1%) efetuaram profilaxia com 3 fármacos, associado a ausência de TARV na gravidez e parto, carga vírica materna >1.000 copias, RM≥4h, RM espontânea e prematuridade. Um recém-nascido (1.3%) faleceu. Nenhuma criança foi infetada. Cerca de um terço (35.5%) apresentou alterações hematológicas e 23 (30.3%) na função hepática, ambas reversíveis. Conclusão: Na população estudada não ocorreu TMF da Infeção VIH1, apesar de apresentar fatores que aumentam o risco de transmissão numa elevada percentagem de casos.Introduction: Human Immunodeficiency Virus type 1 (HIV1) infection in children is almost related to mother-to-child transmission (MTCT). Without prophylaxis transmission rates are 15-25%. With appropriate prophylaxis <2% rates are achieved. Objective: Evaluate the MTCT of HIV infection in a maternity. Materials and Methods: Retrospective study, with review of clinical files of children whose mothers have HIV1 infection, born at Julio Dinis Maternity from January 2006 to December 2011. Not infected was defined if 2 virologic tests were negative (one after 4 months of age) with no clinical signs of infection. Statistical analysis was performed with Epi-Info R v.3.5.1 (Fisher test, p <0.05). Results: Seventy seven children were born from HIV1 infected mothers, 45 (58.4%) males and 15 (19.5%) preterm infants. Diagnosis of maternal infection during pregnancy occurred in 24 (31.6%) and one at childbirth (1.3%). Seven (9.2%) hadn’t had antiretroviral therapy (ART) during pregnancy and 9 (12.3%) had viral load> 1,000 copies at childbirth. Normal delivery occurred in 4 (5.2%) and 10 (13%) had rupture of membranes (RM) ≥ 4h. None was breastfed. All received prophylaxis in the neonatal period; 17 (22.1%) with 3 drugs, associated with absence of ART in pregnancy and at childbirth, maternal viral load> 1,000 copies, RM ≥ 4h, spontaneous RM and prematurity. One newborn (1.3%) died. No child became infected. Almost a third (35.5%) had hematological toxicity and 23 (30.3%) had hepatic toxicity, both reversible. Conclusion: In the population studied no MTCT of HIV1 infection occurred, despite the presence of factors that increase the risk of transmission in a high percentage of cases

Hybrid metabolic flux analysis: combining stoichiometric and statistical constraints to model the formation of complex recombinant products

<p>Abstract</p> <p>Background</p> <p>Stoichiometric models constitute the basic framework for fluxome quantification in the realm of metabolic engineering. A recurrent bottleneck, however, is the establishment of consistent stoichiometric models for the synthesis of recombinant proteins or viruses. Although optimization algorithms for <it>in silico </it>metabolic redesign have been developed in the context of genome-scale stoichiometric models for small molecule production, still rudimentary knowledge of how different cellular levels are regulated and phenotypically expressed prevents their full applicability for complex product optimization.</p> <p>Results</p> <p>A hybrid framework is presented combining classical metabolic flux analysis with projection to latent structures to further link estimated metabolic fluxes with measured productivities. We first explore the functional metabolic decomposition of a baculovirus-producing insect cell line from experimental data, highlighting the TCA cycle and mitochondrial respiration as pathways strongly associated with viral replication. To reduce uncertainty in metabolic target identification, a Monte Carlo sampling method was used to select meaningful associations with the target, from which 66% of the estimated fluxome had to be screened out due to weak correlations and/or high estimation errors. The proposed hybrid model was then validated using a subset of preliminary experiments to pinpoint the same determinant pathways, while predicting the productivity of independent cultures.</p> <p>Conclusions</p> <p>Overall, the results indicate our hybrid metabolic flux analysis framework is an advantageous tool for metabolic identification and quantification in incomplete or ill-defined metabolic networks. As experimental and computational solutions for constructing comprehensive global cellular models are in development, the contribution of hybrid metabolic flux analysis should constitute a valuable complement to current computational platforms in bridging the metabolic state with improved cell culture performance.</p

Cell functional enviromics: Unravelling the function of environmental factors

<p>Abstract</p> <p>Background</p> <p>While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales.</p> <p>Results</p> <p>Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait.</p> <p>Conclusion</p> <p>Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.</p

One-Loop Effective Action for Euclidean Maxwell Theory on Manifolds with Boundary

This paper studies the one-loop effective action for Euclidean Maxwell theory about flat four-space bounded by one three-sphere, or two concentric three-spheres. The analysis relies on Faddeev-Popov formalism and $\zeta$-function regularization, and the Lorentz gauge-averaging term is used with magnetic boundary conditions. The contributions of transverse, longitudinal and normal modes of the electromagnetic potential, jointly with ghost modes, are derived in detail. The most difficult part of the analysis consists in the eigenvalue condition given by the determinant of a $2 \times 2$ or $4 \times 4$ matrix for longitudinal and normal modes. It is shown that the former splits into a sum of Dirichlet and Robin contributions, plus a simpler term. This is the quantum cosmological case. In the latter case, however, when magnetic boundary conditions are imposed on two bounding three-spheres, the determinant is more involved. Nevertheless, it is evaluated explicitly as well. The whole analysis provides the building block for studying the one-loop effective action in covariant gauges, on manifolds with boundary. The final result differs from the value obtained when only transverse modes are quantized, or when noncovariant gauges are used.Comment: 25 pages, Revte

Metabolic flux understanding of Pichia pastoris grown on heterogenous culture media

[EN] Within the emergent field of Systems Biology, mathematical models obtained from physical chemical laws (the so-called first principles-based models) of microbial systems are employed to discern the principles that govern cellular behaviour and achieve a predictive understanding of cellular functions. The reliance on this biochemical knowledge has the drawback that some of the assumptions (specific kinetics of the reaction system, unknown dynamics and values of the model parameters) may not be valid for all the metabolic possible states of the network. In this uncertainty context, the combined use of fundamental knowledge and data measured in the fermentation that describe the behaviour of the microorganism in the manufacturing process is paramount to overcome this problem. In this paper, a grey modelling approach is presented combining data-driven and first principles information at different scales, developed for Pichia pastoris cultures grown on different carbon sources. This approach will allow us to relate patterns of recombinant protein production to intracellular metabolic states and correlate intra and extracellular reactions in order to understand how the internal state of the cells determines the observed behaviour in P. pastoris cultivations.Research in this study was partially supported by the Spanish Ministry of Science and Innovation and FEDER funds from the European Union through grants DPI2011-28112-C04-01 and DPI2011-28112-C04-02. The authors are also grateful to Biopolis SL for supporting this research. We also gratefully acknowledge Associate Professor Jose Camacho for providing the Exploratory Data Analysis Toolbox.González Martínez, JM.; Folch-Fortuny, A.; Llaneras Estrada, F.; Tortajada Serra, M.; Picó Marco, JA.; Ferrer, A. (2014). Metabolic flux understanding of Pichia pastoris grown on heterogenous culture media. Chemometrics and Intelligent Laboratory Systems. 134:89-99. https://doi.org/10.1016/j.chemolab.2014.02.003S899913

Dinâmicas de (investig)ação em contextos de promoção da língua portuguesa: a presença do CIDTFF na rede Camões, I.P.

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The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis

Lohr V, Haedicke O, Genzel Y, et al. The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis. BMC Biotechnology. 2014;14(1): 72.Background: In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to adapt to modern vaccine production. Therefore, we derived previously a continuous suspension cell line, AGE1.CR.pIX, from muscovy duck and established chemically-defined media for virus propagation. Results: To better understand vaccine production processes, we developed a stoichiometric model of the central metabolism of AGE1.CR.pIX cells and applied flux variability and metabolic flux analysis. Results were compared to literature dealing with mammalian and insect cell culture metabolism focusing on the question whether cultured avian cells differ in metabolism. Qualitatively, the observed flux distribution of this avian cell line was similar to distributions found for mammalian cell lines (e.g. CHO, MDCK cells). In particular, glucose was catabolized inefficiently and glycolysis and TCA cycle seem to be only weakly connected. Conclusions: A distinguishing feature of the avian cell line is that glutaminolysis plays only a minor role in energy generation and production of precursors, resulting in low extracellular ammonia concentrations. This metabolic flux study is the first for a continuous avian cell line. It provides a basis for further metabolic analyses to exploit the biotechnological potential of avian and vertebrate cell lines and to develop specific optimized cell culture processes, e.g. vaccine production processes