Previsão e análise da estrutura e dinâmica de redes biológicas

Increasing knowledge about the biological processes that govern the dynamics of living organisms has fostered a better understanding of the origin of many diseases as well as the identification of potential therapeutic targets. Biological systems can be modeled through biological networks, allowing to apply and explore methods of graph theory in their investigation and characterization. This work had as main motivation the inference of patterns and rules that underlie the organization of biological networks. Through the integration of different types of data, such as gene expression, interaction between proteins and other biomedical concepts, computational methods have been developed so that they can be used to predict and study diseases. The first contribution, was the characterization a subsystem of the human protein interactome through the topological properties of the networks that model it. As a second contribution, an unsupervised method using biological criteria and network topology was used to improve the understanding of the genetic mechanisms and risk factors of a disease through co-expression networks. As a third contribution, a methodology was developed to remove noise (denoise) in protein networks, to obtain more accurate models, using the network topology. As a fourth contribution, a supervised methodology was proposed to model the protein interactome dynamics, using exclusively the topology of protein interactions networks that are part of the dynamic model of the system. The proposed methodologies contribute to the creation of more precise, static and dynamic biological models through the identification and use of topological patterns of protein interaction networks, which can be used to predict and study diseases.O conhecimento crescente sobre os processos biológicos que regem a dinâmica dos organismos vivos tem potenciado uma melhor compreensão da origem de muitas doenças, assim como a identificação de potenciais alvos terapêuticos. Os sistemas biológicos podem ser modelados através de redes biológicas, permitindo aplicar e explorar métodos da teoria de grafos na sua investigação e caracterização. Este trabalho teve como principal motivação a inferência de padrões e de regras que estão subjacentes à organização de redes biológicas. Através da integração de diferentes tipos de dados, como a expressão de genes, interação entre proteínas e outros conceitos biomédicos, foram desenvolvidos métodos computacionais, para que possam ser usados na previsão e no estudo de doenças. Como primeira contribuição, foi proposto um método de caracterização de um subsistema do interactoma de proteínas humano através das propriedades topológicas das redes que o modelam. Como segunda contribuição, foi utilizado um método não supervisionado que utiliza critérios biológicos e topologia de redes para, através de redes de co-expressão, melhorar a compreensão dos mecanismos genéticos e dos fatores de risco de uma doença. Como terceira contribuição, foi desenvolvida uma metodologia para remover ruído (denoise) em redes de proteínas, para obter modelos mais precisos, utilizando a topologia das redes. Como quarta contribuição, propôs-se uma metodologia supervisionada para modelar a dinâmica do interactoma de proteínas, usando exclusivamente a topologia das redes de interação de proteínas que fazem parte do modelo dinâmico do sistema. As metodologias propostas contribuem para a criação de modelos biológicos, estáticos e dinâmicos, mais precisos, através da identificação e uso de padrões topológicos das redes de interação de proteínas, que podem ser usados na previsão e no estudo doenças.Programa Doutoral em Engenharia Informátic

Use efficiency of nitrogen, phosphorus and potassium by potato cultivars

Knowledge about nutrients use efficiency in production of tubers in different potato varieties provides important basis to optimize the use of fertilizers in the crop. Thus, this study aimed to determine the productivity and the coefficient of biological utilization (kg of dry matter produced per kg of accumulated nutrient) of nitrogen (N), phosphorus (P) and potassium (K) of thirteen potato cultivars, and compare the extraction and the exportation of N, P and K of Ágata, Asterix and Atlantic cultivars that present low, medium and high content of dry matter, respectively. The treatments consisted of thirteen potato cultivars: Ágata, Atlantic, FL2215, FL2027, FL1867, FL2221, Asterix, BRSIPR Bel, Cupido, Nicolet, Accumulator, Verdi and Taurus. FL2027 cultivar was more productive. The cultivars differs as the coefficient of biological utilization of N, P and K. The Atlantic cultivar extracted and exported more N, P and K than Ágata and Asterix

Juventude cultura e educação de jovens e adultos no âmbito da gestão das escolas publicas do município de Juiz de Fora

-Os objetivos da pesquisa são compreender as diferentes perspectivas que os sujeitos coletivos e individuais envolvidos com a Educação de Jovens e Adultos desenvolvem acerca das questões que afetam a juventude na sociedade brasileira; refletir sobre os processos de juvenilização da Educação de Jovens e Adultos a partir da gestão das escolas públicas; analisar as articulações que se têm estabelecido, no âmbito da gestão das escolas públicas, entre movimentos da juventude, produção de processos culturais e expansão da Educação de Jovens e Adultos; contribuir para que os gestores possam perceber as questões da juventude como uma estratégia que permite a democratização, a socialização e a apropriação da cultura, do conhecimento e dos direitos à educação na EJA. O processo metodológico envolve basicamente duas dimensões. Uma refere-se à discussão teórica cuja revisão bibliográfica buscará mostrar as relações entre juventude, cultura e Educação de Jovens e Adultos. A segunda dimensão apresenta critérios para a definição das escolas públicas de Juiz de Fora que participarão da pesquisa de campo. Neste primeiro ano de pesquisa foi necessário um denso estudo teórico e metodológico a respeito da questão da juventude e da cultura. Por este motivo a fase de observação das escolas ainda não foi realizada. Sendo assim a pesquisa se encontra em andamento

The Importance of C4d in Biopsies of Kidney Transplant Recipients

Antibody-mediated rejection (AMR) is highly detrimental to the prolonged survival of transplanted kidneys. C4d has been regarded as a footprint of AMR tissue damage, and the introduction of C4d staining in daily clinical practice aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. Despite the general acceptance of the usefulness of C4d in the identification of acute AMR, the data for C4d staining in chronic AMR is variable. The presence of C4d in the majority of the biopsies with features of chronic antibody-mediated rejection is reported, but this rejection without C4d staining is observed as well, suggesting that C4d is specific but not sensitive. Further studies on AMR with positive C4d staining in biopsy specimens are really important, as well as the study of novel routine markers that may participate in the pathogenesis of this process

Brazilian version of the Clinical COPD Questionnaire, administered by interview:reliability and validity measurement properties

OBJECTIVE: To test the reliability, validity, and interpretability of the Brazilian version of the Clinical COPD Questionnaire (CCQ) in patients with COPD. METHODS: Fifty patients with COPD completed the CCQ by interview on two occasions. At the first visit, the CCQ was administered twice, by two different raters, approximately 10 min apart; the patients also underwent spirometry and were administered the COPD Assessment Test, the modified Medical Research Council scale, and Saint George’s Respiratory Questionnaire (SGRQ). At the second visit (1-2 weeks later), the CCQ was readministered. We tested the hypothesis that the CCQ total score would correlate positively with the total and domain SGRQ scores (r ≥ 0.5). RESULTS: Of the 50 patients, 30 (60%) were male. The mean age was 66 ± 8 years, and the mean FEV(1) was 44.7 ± 17.9% of the predicted value. For all CCQ items, Cronbach’s alpha coefficient (95% CI) was 0.93 (0.91-0.96). To analyze the interrater reliability and test-retest reliability of the CCQ, we calculated the two-way mixed effects model/single measure type intraclass correlation coefficient (0.97 [95% CI: 0.95-0.98] and 0.92 [95% CI: 0.86-0.95], respectively); the agreement standard error of measurement (0.65 for both); the smallest detectable change at the individual level (1.81 and 1.80, respectively) and group level (0.26 and 0.25, respectively); and the limits of agreement (−0.58 to 0.82 and −1.14 to 1.33, respectively). The CCQ total score correlated positively with all SGRQ scores (r ≥ 0.70 for all). CONCLUSIONS: The Brazilian version of the CCQ showed an indeterminate measurement error, as well as satisfactory interrater/test-retest reliability and construct validity

Functional characterization of a xylose transporter in Aspergillus nidulans

BACKGROUND: The production of bioethanol from lignocellulosic feedstocks will only become economically feasible when the majority of cellulosic and hemicellulosic biopolymers can be efficiently converted into bioethanol. The main component of cellulose is glucose, whereas hemicelluloses mainly consist of pentose sugars such as D-xylose and L-arabinose. The genomes of filamentous fungi such as A. nidulans encode a multiplicity of sugar transporters with broad affinities for hexose and pentose sugars. Saccharomyces cerevisiae, which has a long history of use in industrial fermentation processes, is not able to efficiently transport or metabolize pentose sugars (e.g. xylose). Subsequently, the aim of this study was to identify xylose-transporters from A. nidulans, as potential candidates for introduction into S. cerevisiae in order to improve xylose utilization. RESULTS: In this study, we identified the A. nidulans xtrD (xylose transporter) gene, which encodes a Major Facilitator Superfamily (MFS) transporter, and which was specifically induced at the transcriptional level by xylose in a XlnR-dependent manner, while being partially repressed by glucose in a CreA-dependent manner. We evaluated the ability of xtrD to functionally complement the S. cerevisiae EBY.VW4000 strain which is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae, XtrD was targeted to the plasma membrane and its expression was able to restore growth on xylose, glucose, galactose, and mannose as single carbon sources, indicating that this transporter accepts multiple sugars as a substrate. XtrD has a high affinity for xylose, and may be a high affinity xylose transporter. We were able to select a S. cerevisiae mutant strain that had increased xylose transport when expressing the xtrD gene. CONCLUSIONS: This study characterized the regulation and substrate specificity of an A. nidulans transporter that represents a good candidate for further directed mutagenesis. Investigation into the area of sugar transport in fungi presents a crucial step for improving the S. cerevisiae xylose metabolism. Moreover, we have demonstrated that the introduction of adaptive mutations beyond the introduced xylose utilization genes is able to improve S. cerevisiae xylose metabolism.We would like to thank the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) for providing financial support. We also thank Dr Eckardt Boles for providing the EBY.VW4000 yeast strain, Dr Ronald Hector for providing the plasmids pRH274 and pRH195, Dr Michel Flipphi for providing the Delta creA4 strain, and the two anonymous reviewers for their comments and suggestions. We also acknowledge the Program project grant GM068087 (PI Jay Dunlap) for providing the deletion cassettes

Foliar indices for carrot crop using the compositional nutrient diagnosis method

Carrot has a high yield potential, which requires an adequate and adaptable nutritional management, according to the needs and demands of each crop. Foliar diagnosis is a tool for adjustment and constant improvement of crop fertilization programs. This study aimed to determine leaf indices and reference values using the compositional nutrient diagnosis (CND) method, at three phenological stages of carrot crops [40 and 70 days after sowing (DAS) and at harvest]. In order to calculate the CND method, a database was created with leaf contents of the nutrients N, P, K, Ca, Mg, S, B, Cu, Mn and Zn and root yields, in commercial carrot crops. The nutrient limitation order was generated according to the fertilization response potential. At 70 DAS and at harvest, Mg and Mn were the most limiting nutrients by deficiency, while Zn was the most limiting by excess at 70 DAS, and P and Ca were the most limiting by excess at harvest. The results indicate that the foliar diagnosis performed with the CND method is only effective for the correction of nutritional disturbances in subsequent crops

The influence of genetic stability on Aspergillus fumigatus virulence and azole resistance

Genetic stability is extremely important for the survival of every living organism, and a very complex set of genes has evolved to cope with DNA repair upon DNA damage. Here, we investigated the Aspergillus fumigatus AtmA (Ataxia-telangiectasia mutated, ATM) and AtrA kinases, and how they impact virulence and the evolution of azole resistance. We demonstrated that A. fumigatus atmA and atrA null mutants are haploid and have a discrete chromosomal polymorphism. The ?atmA and ?atrA strains are sensitive to several DNA-damaging agents, but surprisingly both strains were more resistant than the wild-type strain to paraquat, menadione, and hydrogen peroxide. The atmA and atrA genes showed synthetic lethality emphasizing the cooperation between both enzymes and their consequent redundancy. The lack of atmA and atrA does not cause any significant virulence reduction in A. fumigatus in a neutropenic murine model of invasive pulmonary aspergillosis and in the invertebrate alternative model Galleria mellonela. Wild-type, ?atmA, and ?atrA populations that were previously transferred 10 times in minimal medium (MM) in the absence of voriconazole have not shown any significant changes in drug resistance acquisition. In contrast, ?atmA and ?atrA populations that similarly evolved in the presence of a subinhibitory concentration of voriconazole showed an ~5-10-fold increase when compared to the original minimal inhibitory concentration (MIC) values. There are discrete alterations in the voriconazole target Cyp51A/Erg11A or cyp51/erg11 and/or Cdr1B efflux transporter overexpression that do not seem to be the main mechanisms to explain voriconazole resistance in these evolved populations. Taken together, these results suggest that genetic instability caused by ?atmA and ?atrA mutations can confer an adaptive advantage, mainly in the intensity of voriconazole resistance acquisition.We thank the Fundação de Amparo a Pesquisa do Estado de São Paulo and the Conselho Nacional de Desenvolvimento Cientí fi co e Tecnológico, Brazil, for fi nancial support. F.R. and B.H.F. were supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (NORTE-01-0145-FEDER-000013)info:eu-repo/semantics/publishedVersio

Niños y adolescentes transgénero brasileños : atributos asociados a la calidad de vida

Objetivo: descrever atributos associados à Qualidade de Vida de crianças e adolescentes transgêneros brasileiros segundo sua própria percepção. Método: estudo descritivo, realizado com 32 participantes entre oito e 18 anos, entrevistados ou que participaram de grupos focais. Os depoimentos foram transcritos, agrupados com auxílio do software Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires, versão 0.7 alpha 2 e descritos segundo a definição da Qualidade de Vida pela Organização Mundial da Saúde no que concerne às dimensões mental, física e social. Resultados: foi possível identificar o núcleo familiar como o principal meio de suporte social das crianças e adolescentes transgêneros. Entretanto, a vivência de preconceito e discriminação foram atributos negativos associados à Qualidade de Vida. Conclusão: os depoimentos indicam que a vida das crianças e adolescentes transgêneros é impactada por fatores sociais, físicos e mentais em virtude do estigma e discriminação vivenciados. Espera-se com esse estudo contribuir para a formulação de políticas públicas relacionadas às crianças e adolescentes transgêneros e ampliar a discussão sobre deveres e direitos dos cidadãos frente à transexualidade.Objective: to describe attributes associated with the Quality of Life of Brazilian transgender children and adolescents according to their own perception. Method: descriptive study conducted with 32 participants between eight and 18 years old, who were either interviewed or participated in focus groups. The statements were transcribed, grouped with the aid of the Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires software, version 0.7 alpha 2 and described according to the definition of Quality of Life by the World Health Organization concerning to the mental, physical, and social dimensions. Results: it was possible to identify the family nucleus as the main social support for transgender children and adolescents. However, the experience of prejudice and discrimination were negative attributes associated with Quality of Life. Conclusion: the statements indicate that lives of transgender children and adolescents are impacted by social, physical, and mental factors due to the stigma and discrimination experienced. It is expected to contribute to the formulation of public policies related to transgender children and adolescents and expand the discussion on the citizens’ duties and rights in relation to transsexuality.Objetivo: describir los atributos asociados a la Calidad de Vida de niños y adolescentes transgénero brasileños, de acuerdo con su percepción. Método: estudio descriptivo, realizado con 32 participantes entre 8 y 18 años, entrevistados o que participaron en grupos focales. Los testimonios se transcribieron y clasificaron con el soporte del software Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires, versão 0.7 alpha 2 y fueron descriptos de acuerdo con la definición de Calidad de Vida de la Organización Mundial de la Salud en lo concerniente a las dimensiones mental, física y social. Resultados: fue posible identificar al núcleo familiar como el principal medio de soporte social para niños y adolescentes transgénero. Sin embargo, haber vivido experiencias de prejuicio y discriminación fueron atributos negativos asociados con la Calidad de Vida. Conclusión: los testimonios indican que la vida de los niños y adolescentes transgénero se ve afectada por factores sociales, físicos y mentales debido al estigma y la discriminación que experimentan. Se espera que este estudio contribuya a la formulación de políticas públicas relacionadas con los niños y adolescentes transgénero y amplíe la discusión sobre los deberes y derechos de los ciudadanos en relación a la transexualidad

Crianças e adolescentes transgêneros brasileiros: atributos associados à qualidade de vida

Objetivo: descrever atributos associados à Qualidade de Vida de crianças e adolescentes transgêneros brasileiros segundo sua própria percepção. Método: estudo descritivo, realizado com 32 participantes entre oito e 18 anos, entrevistados ou que participaram de grupos focais. Os depoimentos foram transcritos, agrupados com auxílio do software Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires, versão 0.7 alpha 2 e descritos segundo a definição da Qualidade de Vida pela Organização Mundial da Saúde no que concerne às dimensões mental, física e social. Resultados: foi possível identificar o núcleo familiar como o principal meio de suporte social das crianças e adolescentes transgêneros. Entretanto, a vivência de preconceito e discriminação foram atributos negativos associados à Qualidade de Vida. Conclusão: os depoimentos indicam que a vida das crianças e adolescentes transgêneros é impactada por fatores sociais, físicos e mentais em virtude do estigma e discriminação vivenciados. Espera-se com esse estudo contribuir para a formulação de políticas públicas relacionadas às crianças e adolescentes transgêneros e ampliar a discussão sobre deveres e direitos dos cidadãos frente à transexualidade.Objective: to describe attributes associated with the Quality of Life of Brazilian transgender children and adolescents according to their own perception. Method: descriptive study conducted with 32 participants between eight and 18 years old, who were either interviewed or participated in focus groups. The statements were transcribed, grouped with the aid of the Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires software, version 0.7 alpha 2 and described according to the definition of Quality of Life by the World Health Organization concerning to the mental, physical, and social dimensions. Results: it was possible to identify the family nucleus as the main social support for transgender children and adolescents. However, the experience of prejudice and discrimination were negative attributes associated with Quality of Life. Conclusion: the statements indicate that lives of transgender children and adolescents are impacted by social, physical, and mental factors due to the stigma and discrimination experienced. It is expected to contribute to the formulation of public policies related to transgender children and adolescents and expand the discussion on the citizens’ duties and rights in relation to transsexuality.Objetivo: describir los atributos asociados a la Calidad de Vida de niños y adolescentes transgénero brasileños, de acuerdo con su percepción. Método: estudio descriptivo, realizado con 32 participantes entre 8 y 18 años, entrevistados o que participaron en grupos focales. Los testimonios se transcribieron y clasificaron con el soporte del software Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires, versão 0.7 alpha 2 y fueron descriptos de acuerdo con la definición de Calidad de Vida de la Organización Mundial de la Salud en lo concerniente a las dimensiones mental, física y social. Resultados: fue posible identificar al núcleo familiar como el principal medio de soporte social para niños y adolescentes transgénero. Sin embargo, haber vivido experiencias de prejuicio y discriminación fueron atributos negativos asociados con la Calidad de Vida. Conclusión: los testimonios indican que la vida de los niños y adolescentes transgénero se ve afectada por factores sociales, físicos y mentales debido al estigma y la discriminación que experimentan. Se espera que este estudio contribuya a la formulación de políticas públicas relacionadas con los niños y adolescentes transgénero y amplíe la discusión sobre los deberes y derechos de los ciudadanos en relación a la transexualidad