Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction

O ciclo glicose-ácido graxo explica a preferência do tecido muscular pelos ácidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercício de alta intensidade, há aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espécies reativas de oxigênio (EROs) durante a atividade muscular sugere que o balanço redox intracelular é importante na regulação do metabolismo de lipídios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteína desacopladora mitocondrial. O efeito oposto é esperado durante a atividade moderada. Assim, as questões levantadas nesta revisão são: Por que o músculo esquelético utiliza preferencialmente os lipídios no estado basal e de atividade moderada? Por que o ciclo glicose-ácido graxo falha em exercer seus efeitos durante o exercício intenso? Como o músculo esquelético regula o metabolismo de lipídios e carboidratos em regime envolvendo o ciclo contração-relaxamento555303313CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãoThe glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle

Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction

O ciclo glicose-ácido graxo explica a preferência do tecido muscular pelos ácidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercício de alta intensidade, há aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espécies reativas de oxigênio (EROs) durante a atividade muscular sugere que o balanço redox intracelular é importante na regulação do metabolismo de lipídios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteína desacopladora mitocondrial. O efeito oposto é esperado durante a atividade moderada. Assim, as questões levantadas nesta revisão são: Por que o músculo esquelético utiliza preferencialmente os lipídios no estado basal e de atividade moderada? Por que o ciclo glicose-ácido graxo falha em exercer seus efeitos durante o exercício intenso? Como o músculo esquelético regula o metabolismo de lipídios e carboidratos em regime envolvendo o ciclo contração-relaxamento.The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle

COVID-19 and mental health of pregnant women in Ceará, Brazil

OBJECTIVE To assess the perceptions of pregnant women about COVID-19 and the prevalence of common mental disorders during the implemented social distancing period. METHODS This was an observational, cross-sectional study using digital media, of pregnant women exposed to social distancing due to the COVID-19 pandemic, in Fortaleza, Ceará, Northeastern Brazil. Common mental disorders were estimated using the modified Self-Report Questionnaire-20 (SRQ-20) scale, and the feelings towards COVID-19 were assessed using the Fear of COVID-19 scale through telephone calls made in May 2020. COX multivariate regression models were used to verify the associations. RESULTS Of the 1,041 pregnant women, 45.7% (95%CI: 42.7–48.8) had common mental disorders (CMD). All items of the Fear of COVID-19 Scale showed a significant association with the prevalence of CMD (p < 0.001). A CMD risk gradient was observed, going from a prevalence ratio of 1.52 (95%CI: 1.13–2.04) in pregnant women with two positive items to 2.70 (95%CI: 2.08–3.51) for those with four positive items. Early gestational age and the lack of prenatal care were also associated with CMD. CONCLUSIONS The prevalence of common mental disorders in pregnant women was high during the period of social distancing and was aggravated by negative feelings towards COVID-19

Estudo da interação molecular do anticorpo 19CC6CG2 com o antígeno HSBSAG por métodos computacionais

Submitted by Repositório Arca ([email protected]) on 2020-01-23T17:03:27Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) artur_sampaio_ioc_mest_2019.pdf: 3030150 bytes, checksum: 3e643ec48809e6fcb5f9c876aa9f636f (MD5)Approved for entry into archive by Márcia Aguiar ([email protected]) on 2020-01-24T19:18:58Z (GMT) No. of bitstreams: 2 artur_sampaio_ioc_mest_2019.pdf: 3030150 bytes, checksum: 3e643ec48809e6fcb5f9c876aa9f636f (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2020-01-24T19:18:58Z (GMT). No. of bitstreams: 2 artur_sampaio_ioc_mest_2019.pdf: 3030150 bytes, checksum: 3e643ec48809e6fcb5f9c876aa9f636f (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.A hepatite B é um problema de saúde global: só no ano de 2015 foram quase 900 mil óbitos decorrentes de complicações relacionadas à infecção com o vírus HBV. No Brasil, a situação também é grave: no ano de 2000 até o ano de 2015 o número de óbitos atingiu 13 mil. O diagnóstico da doença e o tratamento dos pacientes crônicos podem ser feitos através do uso de imunoglobulinas que tem afinidade pelo antígeno de superfície do vírus, HBsAg. Portanto, estratégias que busquem diminuir os custos de produção de imunoglobulinas anti-HBsAg ou aumentar sua afinidade frente a este antígeno são desejáveis em âmbitos nacional e global. O estudo de biomoléculas através de técnicas computacionais tem produzido bons resultados, capazes de orientar estudos experimentais, economizando tempo e recursos e, frequentemente, resolvendo problemas biológicos. Dentre estas técnicas computacionais, destaca-se o cálculo de energia livre. A aplicação do cálculo de energia livre a complexos anticorpo-antígeno pode fornecer informações detalhadas sobre a afinidade do anticorpo frente ao antígeno. Neste trabalho, estudamos a interação do anticorpo 19CC6CG2, desenvolvido no Laboratório de Tecnologia de Anticorpos Monoclonais de Bio-Manguinhos, com o HBsAg através de duas técnicas de cálculo de energia livre: MM-PBSA e Adaptive Biasing Force Embora a primeira técnica tenha fornecido um valor de \0394G de ligação de -12 kcal/mol, a análise mais robusta através do segundo método mostrou um \0394G de dissociação de -7,6 kcal/mol. Adicionalmente, foram propostas mutações na estrutura do anticorpo visando ao aumento da sua afinidade pelo antígeno. O anticorpo mutante foi então modelado in silico e a sua afinidade frente ao HBsAg foi mensurada através da técnica de ABF. Resultados preliminares mostraram um valor de \0394G de ligação de -4,2 kcal/mol. As mutações na estrutura do anticorpo favoreceram a formação de ligações hidrogênio e pontes salinas intermoleculares mais estáveis nas simulações de dinâmica molecular. No entanto, simulações mais longas e/ou o aumento da dimensionalidade do espaço através de variáveis coletivas no cálculo de ABF, podem melhorar a convergência do método, tornando evidente se as mutações aqui propostas são favoráveis à afinidade do anticorpo 19CC6CG2 contra o HBsAg.Hepatitis B is a global health problem: only in 2015 there were almost 900 thousand deaths caused by complications related to HBV infection. In Brazil, the situation is also serious: from year 2000 to 2015 the number of deaths reached 13 thousand. Diagnosis of the disease and treatment of chronic patients can be done using immunoglobulins that have affinity for the virus surface antigen, HBsAg. Therefore, strategies that seek either to decrease the production costs of anti-HBsAg immunoglobulins or to increase their affinity against this antigen are desirable at national and global levels. The study of biomolecules through computational techniques has produced good results, capable of guiding experimental studies, saving time and resources, and often solving biological problems. Among these computational techniques, the free energy calculation stands out. The application of the free energy calculation to antibody-antigen complexes can provide detailed information on the affinity of the antibody against the antigen. In this work, we studied the interaction of the 19CC6CG2 antibody, which was developed in the Bio-Manguinhos Monoclonal Antibody Technology Laboratory, against HBsAg through two free energy calculation techniques: MM-PBSA and Adaptive Biasing Force. Although the first technique provided a ΔG binding value of -12 kcal/mol, the more robust analysis through the second method showed a dissociation ΔG of -7,6 kcal/mol. In addition, mutations were proposed in the structure of the antibody aiming to increase its affinity for the antigen. The mutant antibody was then modeled in silico and its affinity against HBsAg was measured through the ABF technique. Preliminary results showed a binding ΔG value of -4,2 kcal/mol. Mutations in the structure of the antibody favored the formation of hydrogen bonds and intermolecular salt bridges which were more stable in molecular dynamics simulations. However, longer simulations and/or increased dimensionality of space through collective variables in the ABF calculation can improve the convergence of the method, making it evident whether the mutations proposed herein are favorable to the affinity of the 19CC6CG2 antibody against HBsAg

Closed orbits and the harmonic Manev potential

Velten H, Sampaio RV. Closed orbits and the harmonic Manev potential. Revista Brasileira de Ensino de Fisica. 2009;31(1): 1301.We study conditions for the existence of closed orbits in three distinct potentials. Firstly, we confirm well known conditions for the Manev problem. In a second step, inspired by the result of Bertrand's theorem, we construct a harmonic Manev potential with a harmonic oscillator term instead of the Newtonian one. As in the original Manev potential we find similar conditions for closed orbits that are correlated with restrict values of angular momenta. We analyse also a harmonic corrected Newtonian potential

Machine learning-aided engineering of a cytochrome P450 for optimal bioconversion of lignin fragments

Using machine learning, molecular dynamics simulations, and density functional theory calculations we gain insight into the selectivity patterns of substrate activation by the cytochromes P450. In nature the reactions catalyzed by the P450s lead to the biodegradation of xenobiotics, but recent work has shown that fungi utilize P450s for the activation of lignin fragments, such as monomer and dimer units. These fragments often are the building blocks of valuable materials, including drug molecules and fragrances, hence a highly selective biocatalyst that can produce these compounds in good yield with high selectivity would be an important step in biotechnology. In this work a detailed computational study is reported on two reaction channels of two P450 isozymes, namely the O-deethylation of guaethol by CYP255A and the O-demethylation versus aromatic hydroxylation of p-anisic acid by CYP199A4. The studies show that the second-coordination sphere plays a major role in substrate binding and positioning, heme access, and in the selectivity patterns. Moreover, the local environment affects the kinetics of the reaction through lowering or raising barrier heights. Furthermore, we predict a site-selective mutation for highly specific reaction channels for CYP199A4

Sugar transport systems in Kluyveromyces marxianus CCT 7735

The pattern of glucose repression in most Kluyveromyces marxianus strains does not correlate with fermentative behaviour; however, glucose repression and fermentative metabolism appear to be linked to the kinetics of sugar uptake. In this work, we show that lactose transport in K. marxianus CCT 7735 by lactose-grown cells is mediated by a low-affinity H+-sugar symporter. This system is glucose repressed and able to transport galactose with low affinity. We also observed the activity of a distinct lactose transporter in response to raffinose. Regarding glucose uptake, specificities of at least three low-affinity systems rely on the carbon source available in a given growth medium. Interestingly, it was observed only one high-affinity system is able to transport both glucose and galactose. We also showed that K. marxianus CCT 7735 regulates the expression of sugar transport systems in response to glucose availability