Molecular determinants for FMN-binding in Desulfovibrio gigas flavoredoxin

Abstract: Flavoredoxin participates in Desulfovibrio gigas thiosulfate reduction pathway. Its 3-dimensional model was generated allowing the oxidized riboflavin-5'-phosphate (FMN) site to be predicted. Residues likely to be involved in FMN-binding were identified (N29, W35, T56, K92, H131 and F164) and mutated to alanine. Fluorescence titration with apoprotein showed that FMN is strongly bound in the wild-type protein. Comparison of K-d values for mutants suggests that interactions with the phosphate group of FMN, contribute more to binding than the interactions with the isoalloxazine ring. The redox potential of bound FMN determined for wild-type and mutants revealed shifts to less negative values. These findings were correlated with the protein structure in order to contribute to a better understanding of the structure-function relationships in flavoredoxin. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Coronary artery bypass surgery and longitudinal evaluation of the autonomic cardiovascular function

INTRODUCTION: Imbalance in autonomic cardiovascular function increases the risk for sudden death in patients with coronary artery disease (CAD), but the time course of the impact of coronary artery bypass grafting (CABG) on autonomic function has been little studied. Thus, the purpose of the present study was to determine the effects of the CABG on the cardiovascular autonomic function. METHODS: Patients undergoing CABG (n = 13) and two matched control groups (patients with CAD who refused surgical treatment [n = 9], and healthy volunteers [n = 9]) underwent a prospective longitudinal study consisting of autonomic evaluation before and after (3, 6, 15, 30, 60, and 90 days) surgery, including measurement of heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and Valsalva maneuver. RESULTS: After CABG there was a decrease in, and a later recovery of, (1) the HRV in the time domain and in the frequency domain, (2) RSA, and (3) Valsalva maneuver. CONCLUSIONS: CABG caused an impairment, reversible after 60 days, of cardiovascular autonomic function, with a maximal decrease on about the sixth day after surgery

Efeitos da terapia de reposição hormonal estroprogestativa sobre o sistema de coagulação e de fibrinólise em mulheres na pós-menopausa

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida

Functional phage display of leech-derived tryptase inhibitor (LDTI): construction of a library and selection of thrombin inhibitors

The recombinant phage antibody system pCANTAB 5E has been used to display functionally active leech-derived tryptase inhibitor (LDTI) on the tip of the filamentous M13 phage, A limited combinatorial library of 5.2 x 10(4) mutants was created with a synthetic LDTI gene, using a degenerated oligonucleotide and the pCANTAB 5E phagemid. the mutations were restricted to the P1-P4' positions of the reactive site. Fusion phages and appropriate host strains containing the phagemids were selected after binding to thrombin and DNA sequencing. the variants LDTI-2T (K8R, I9V, S10, K11W, P12A), LDTI-5T (K8R, I9V, S10, K11S, P12L) and LDTI-10T (K8R, I9L, S10, K11D, P12I) were produced with a Saccharomyces cerevisiae expression system. the new inhibitors, LDTI-2T and -5T, prolong the blood clotting time, inhibit thrombin (Ki 302 nM and 28 nM) and trypsin (K-i 6.4 nM and 2.1 nM) but not factor Xa, plasma kallikrein or neutrophil elastase, the variant LDTI-10T binds to thrombin but does not inhibit it, the relevant reactive site sequences of the thrombin inhibiting variants showed a strong preference for arginine in position P1 (K8R) and for valine in P1' (I9V), the data indicate further that LDTI-5T might be a model candidate for generation of active-site directed thrombin inhibitors and that LDTI in general may be useful to generate specific inhibitors suitable for a better understanding of enzyme-inhibitor interactions. (C) 1999 Federation of European Biochemical Societies.UNIFESP, Dept Bioquim, EPM, BR-04044020 São Paulo, BrazilUniv Munich, Klinikum Innenstadt, Chirurg Klin & Poliklin, Klin Chem & Klin Biochem Abt, D-8000 Munich, GermanyUNIFESP, Dept Med, Disciplina Hematol, EPM, BR-04044020 São Paulo, BrazilUNIFESP, Dept Bioquim, EPM, BR-04044020 São Paulo, BrazilUNIFESP, Dept Med, Disciplina Hematol, EPM, BR-04044020 São Paulo, BrazilWeb of Scienc

Strain-inducing photochemical chlorination of graphene nanoribbons on SiC (0001)

As different low-dimensional materials are sought to be incorporated into microelectronic devices, graphene integration is dependent on the development of band gap opening strategies. Amidst the different methods currently investigated, application of strain and use of electronic quantum confinement have shown promising results. In the present work, epitaxial graphene nanoribbons (GNR), formed by surface graphitization of SiC (0001) on crystalline step edges, were submitted to photochemical chlorination. The incorporation of Cl into the buffer layer underlying graphene increased the compressive uniaxial strain in the ribbons. Such method is a promising tool for tuning the band gap of GNRs

Academic expectations of students in the first years of Higher Education

This study analyzed students' expectations in the transition to Higher Education. Participants were 205 students of the first and second year, enrolled in public and private Higher Education institutions. Students answered an open questionnaire composed of five questions about personal expectations, interpersonal relationships, expectations about the undergraduate program and career development, the institution where they were enrolled, and a social-demographic questionnaire. Content analysis was performed to analyze data. Students described their own expectations regarding the job market, and personal and occupational benefits from studying in Higher Education. These results support previous studies that have suggested that first-year students present high expectations about higher education. We discuss the implications of the results in future researches and intervention with students, especially the ones with difficulties in academic adaptation.Este trabalho analisa expectativas acadêmicas de universitários ao ingressar no Ensino Superior. Participaram do estudo 205 estudantes do primeiro e segundo ano do Ensino Superior. Os participantes responderam a um questionário sobre expectativas pessoais, relações interpessoais, expectativas acerca do curso, carreira, instituição de ensino e um questionário de dados sociodemográficos. Os dados foram submetidos a análises qualitativas, com recurso a análise de conteúdo. Os alunos descrevem suas expectativas em direção ao mercado de trabalho e aos ganhos pessoais e profissionais resultantes do fato de cursarem o Ensino Superior. Esses resultados reiteram estudos anteriores, indicando que alunos do primeiro ano apresentam altas expectativas em relação ao Ensino Superior. Discutem-se as implicações dos resultados para novas pesquisas e intervenções com universitários, especialmente aqueles com dificuldades de adaptação acadêmica.info:eu-repo/semantics/publishedVersio

O ensino de Ciências e Matemática na educação de jovens e adultos: um estudo de caso sobre ação docente

Apresentamos um estudo de caso que analisou como se efetiva a ação pedagógica nas aulas de ciências na EJA. Os resultados foram construidos a partir de questionários aplicados a discentes e docentes de ciências da ultíma série da EJA de uma escola estadual de Goiás. Outros instrumentos de coleta de dados foram as anotações em diário de campo das observações das aulas por meio do estágio suprevisionado. A investigação permitiu caracterizar o perfil dos sujeitos pesquisados e estabelecer comparação com a literatura específica.No que se refere aos professores, analisamos sua prática e formação para lecionar com o público de EJA.Conclui-se que o trabalho apontou questões que desvelam a ação pedagógica e contribuem com futuras ações nesta modalidade de ensino

Healthy maternal bonding as a resilience factor for depressive disorder

INTRODUCTION: Depressive disorders (DDs) are very prevalent disorders particularly in women, a high-risk gender group. Determining the risk and protective factors associated with the development of DDs is fundamental to planning preventive and therapeutic strategies. In this study, we evaluated the correlations between healthy maternal attachment and the development of DDs in adulthood. METHODS: We evaluated 52 women at 6 months to 1 year after premature childbirth at Maternidade Vila Nova Cachoeirinha. They were evaluated using the following instruments: Brazilian Criteria of Economic Classification,Parental Bonding Inventory (PBI),Center for Epidemiologic Studies Depression Scale (CES-D), and Edinburgh Postnatal Depression Scale (EPDS). Cut-off scores on the CES-D and EPDS were used to classifythe subjects as currently having a DD or having probable postpartum disorder (PPD) after childbirth. Multiple logistic regression was used to evaluate the risk factors associated with DDs. RESULTS: We found that 49.1% of the sample had a current depressive episode, and 73.6% had probable PPD. Based on logistic regression, current depression (odds ratio = 1.092 [confidence interval: 1.005; 1.186]), and a PPD (odds ratio = 1.108 [confidence interval: 1.011; 1.21]) were negatively correlated with affective maternal relationships. CONCLUSIONS: Women who reported healthy attachment with their mothers did not develop DDs when faced with stressful situations such as premature childbirth

Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes

Neuropsychiatric disorders and type 2 diabetes (T2D) are major public health concerns proposed to be intimately connected. T2D is associated with increased risk of dementia, neuropsychiatric and mood disorders. Evidences of the involvement of insulin signaling on brain mechanisms related to depression indicate that insulin resistance, a hallmark of type 2 diabetes, could develop in the brains of depressive patients. In this article, we briefly review possible molecular mechanisms associating defective brain insulin signaling with reward system, neurogenesis, synaptic plasticity and hypothalamic-pituitary-adrenal (HPA) stress axis in depression. We further discuss the involvement of tumor necrosis factor α (TNFα) promoting defective insulin signaling and depressive-like behavior in rodent models. Finally, due to the high resistant rate of anti-depressants, novel insights into the link between insulin resistance and depression may advance the development of alternative treatments for this disease

Divergence via Europeanisation: rethinking the origins of the Portuguese debt crisis

A founding myth of the euro was that profound economic convergence could be achieved across the core and periphery of Europe. Scholarship from within Comparative Political Economy (CPE) has compellingly pointed to this myth of convergence as the fundamental mistake of the euro project (Regan, “Imbalance of Capitalisms”). Economic and Monetary Union was applied across a range of incompatible varieties of capitalism with little appreciation for how difficult it would be for peripheral economies to overcome long-standing institutional stickiness. Yet, while institutional stickiness tells us much about the causes of declining competitiveness, it tells us much less about the origins of brand new patterns of debt-led growth. This article modifies this CPE account by drawing attention to the much overlooked case of Portugal. In contrast to CPE’s emphasis on institutional stickiness, this paper explores the ways in which negotiation of European integration has been generative of institutional transformation leading to debt-led growth in Portugal. By combining Europeanisation with CPE, this article shows that, far from an inability to do so, in the case of Portugal, it has been the attempt to ‘follow the rules’ of European Integration that explains its damaging patterns of debt-led growth