RESUMO
La reproducción sexual es la forma de propagación más antigua y universal utilizada por los vertebrados. Los mecanismos que controlan la determinación sexual y la diferenciación en estos animales son diversos y dependen de una amplia variedad de factores genéticos, así como en algunos casos de factores ambientales. El sexo genético puede definirse por factores genéticos hereditarios que se determinan en la fertilización. Por otro lado, la diferenciación gonadal depende de la activación de factores transcripcionales que se expresan durante la ventana de diferenciación sexual. Dichos factores pueden tener su expresión alterada por condiciones ambientales como la temperatura y la osmolaridad, entre otros. Estos procesos sexuales se dividen clásicamente en determinación y diferenciación sexual, respectivamente. Con base en tales hechos, esta revisión tiene como objetivo mostrar los fundamentos básicos de los procesos de determinación y diferenciación sexual en vertebrados, enfatizando el grupo de peces teleósteos.(AU)
Sexual reproduction is the oldest and universal form of propagation used by vertebrates. The mechanisms that control sexual determination and differentiation in these animals are diverse and depend on a wide variety of genetic factors as well as in some cases environmental factors. Genetic sex can be define by hereditary genetic factors that are determined in fertilization. On the other hand, gonadal differentiation depends on the activation of transcriptional factors that are expressed during the sexual differentiation window. Such factors may have their expression altered by environmental conditions such as temperature and osmolarity, among others. These sexual processes are classically divided into sexual determination and differentiation, respectively. Based on such facts, this review aims to show the basic theoretical reasoning of the processes of sexual determination and differentiation in vertebrates, emphasizing the group of teleost fishes.(AU)
A reprodução sexual é a forma de propagação mais antiga e universal utilizada pelos vertebrados. Os mecanismos que controlam a determinação e diferenciação sexual nestes animais são diversos e dependem de uma grande variedade de fatores genéticos bem como em alguns casos de fatores ambientais. O sexo genético pode ser definido por fatores genéticos hereditários que são determinados na fecundação. Por outro lado, a diferenciação gonadal depende da ativação de fatores transcricionais que são expressos durante a janela de diferenciação sexual. Tais fatores podem ter sua expressão alterada por condições ambientais como a temperatura e a osmolaridade dentre outros. Estes processos sexuais são classicamente divididos em determinação e diferenciação sexual, respectivamente. Baseados em tai fatos, esta revisão tem como objetivo mostrar a fundamentação básica dos processos de determinação e diferenciação sexual em vertebrados com ênfase no grupo dos peixes teleósteos.(AU)
Assuntos
Animais , Masculino , Feminino , Vertebrados/anatomia & histologia , Análise para Determinação do Sexo/métodos , Análise para Determinação do Sexo/veterinária , GônadasRESUMO
La reproducción sexual es la forma de propagación más antigua y universal utilizada por los vertebrados. Los mecanismos que controlan la determinación sexual y la diferenciación en estos animales son diversos y dependen de una amplia variedad de factores genéticos, así como en algunos casos de factores ambientales. El sexo genético puede definirse por factores genéticos hereditarios que se determinan en la fertilización. Por otro lado, la diferenciación gonadal depende de la activación de factores transcripcionales que se expresan durante la ventana de diferenciación sexual. Dichos factores pueden tener su expresión alterada por condiciones ambientales como la temperatura y la osmolaridad, entre otros. Estos procesos sexuales se dividen clásicamente en determinación y diferenciación sexual, respectivamente. Con base en tales hechos, esta revisión tiene como objetivo mostrar los fundamentos básicos de los procesos de determinación y diferenciación sexual en vertebrados, enfatizando el grupo de peces teleósteos.
Sexual reproduction is the oldest and universal form of propagation used by vertebrates. The mechanisms that control sexual determination and differentiation in these animals are diverse and depend on a wide variety of genetic factors as well as in some cases environmental factors. Genetic sex can be define by hereditary genetic factors that are determined in fertilization. On the other hand, gonadal differentiation depends on the activation of transcriptional factors that are expressed during the sexual differentiation window. Such factors may have their expression altered by environmental conditions such as temperature and osmolarity, among others. These sexual processes are classically divided into sexual determination and differentiation, respectively. Based on such facts, this review aims to show the basic theoretical reasoning of the processes of sexual determination and differentiation in vertebrates, emphasizing the group of teleost fishes.
A reprodução sexual é a forma de propagação mais antiga e universal utilizada pelos vertebrados. Os mecanismos que controlam a determinação e diferenciação sexual nestes animais são diversos e dependem de uma grande variedade de fatores genéticos bem como em alguns casos de fatores ambientais. O sexo genético pode ser definido por fatores genéticos hereditários que são determinados na fecundação. Por outro lado, a diferenciação gonadal depende da ativação de fatores transcricionais que são expressos durante a janela de diferenciação sexual. Tais fatores podem ter sua expressão alterada por condições ambientais como a temperatura e a osmolaridade dentre outros. Estes processos sexuais são classicamente divididos em determinação e diferenciação sexual, respectivamente. Baseados em tai fatos, esta revisão tem como objetivo mostrar a fundamentação básica dos processos de determinação e diferenciação sexual em vertebrados com ênfase no grupo dos peixes teleósteos.
Assuntos
Masculino , Feminino , Animais , Análise para Determinação do Sexo/métodos , Análise para Determinação do Sexo/veterinária , Gônadas , Vertebrados/anatomia & histologiaRESUMO
Industrial areas on estuarine systems are commonly affected by heavy metals, affecting all local biota. Random Amplified Polymorphic DNA (RAPD) was used to evaluate genetic diversity of Ucides cordatus at mangroves in southeastern Brazil (Juréia, J; São Vicente, SV; and Cubatão, C), with distinct pollution levels by metals. The genetic diversity of this species was compared with concentrations of metals (Cd, Pb, Cu, Cr and Hg) in the environment. A pollution gradient was confirmed (SV>C>J), with low levels detected in water, except for mercury in SV. All metals in the sediment samples were below Threshold Effect Level (TEL), without an apparent biological risk to the biota. Genetic distance was very similar between J and C, with SV occurring as an out-group. RAPD was a powerful tool to investigate the effect of metal pollution on genetic diversity of this mangrove crab, and to evaluate the conservation status of the mangrove ecosystem.
Assuntos
Braquiúros/genética , Monitoramento Ambiental , Variação Genética , Metais Pesados , Poluentes Químicos da Água , Animais , Conservação dos Recursos Naturais , Ecossistema , Técnica de Amplificação ao Acaso de DNA Polimórfico , RhizophoraceaeRESUMO
l-asparaginase (l-asparagine amino hydrolase, E.C.3.5.1.1) is an enzyme clinically accepted as an antitumor agent to treat acute lymphoblastic leukemia and lymphosarcoma. It catalyzes l-asparagine (Asn) hydrolysis to l-aspartate and ammonia, and Asn effective depletion results in cytotoxicity to leukemic cells. Microbial l-asparaginase (ASNase) production has attracted considerable attention owing to its cost effectiveness and eco-friendliness. The focus of this review is to provide a thorough review on microbial ASNase production, with special emphasis to microbial producers, conditions of enzyme production, protein engineering, downstream processes, biochemical characteristics, enzyme stability, bioavailability, toxicity and allergy potential. Some issues are also highlighted that will have to be addressed to achieve better therapeutic results and less side effects of ASNase use in cancer treatment: (a) search for new sources of this enzyme to increase its availability as a drug; (b) production of new ASNases with improved pharmacodynamics, pharmacokinetics and toxicological profiles, and (c) improvement of ASNase production by recombinant microorganisms. In this regard, rational protein engineering, directed mutagenesis, metabolic flux analysis and optimization of purification protocols are expected to play a paramount role in the near future.
Assuntos
Antineoplásicos , Asparaginase , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Asparaginase/química , Asparaginase/metabolismo , Asparaginase/uso terapêutico , Bactérias/metabolismo , Composição de Medicamentos , Fungos/metabolismo , Engenharia de ProteínasRESUMO
ABSTRACT The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN α, β, and γ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.
Assuntos
Produtos Biológicos , Biotecnologia , Preparações Farmacêuticas , Técnicas Microbiológicas , Proteínas Recombinantes , Indústria Farmacêutica , Fermentação , Medicamentos BiossimilaresRESUMO
The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN , , and ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.(AU)
Assuntos
Produtos Biológicos/química , Biofarmácia , Biotecnologia , Fermentação , Corrente JusanteRESUMO
The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN α, ß, and γ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.
Assuntos
Produtos Biológicos , Biotecnologia , Técnicas Microbiológicas , Preparações Farmacêuticas , Medicamentos Biossimilares , Indústria Farmacêutica , Fermentação , Humanos , Proteínas RecombinantesRESUMO
ABSTRACT The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN , , and ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.
RESUMO
INTRODUÇÃO: Diferentes parâmetros hemodinâmicos, incluindo os indicadores estáticos de pré-carga cardíaca como o índice de volume diastólico final ventrículo direito (IVDFVD) e parâmetros dinâmicos como a variação de pressão de pulso (VPP) têm sido usados na tomada de decisão para considerar o processo da expansão volêmica em pacientes em estado grave. O objetivo deste estudo foi comparar a reanimação por fluidos guiados tanto por VPP ou IVDFVD após choque hemorrágico induzido experimentalmente. MÉTODO: vinte e seis suínos anestesiados e ventilados mecanicamente foram alocados em três grupos: controle (Grupo I), VPP (Grupo II) e IVDFVD (Grupo III). Foi induzido choque hemorrágico por retirada de sangue até atingir a pressão arterial média de 40mmhg, que foi mantida por 60 minutos. Parâmetros foram medidos no tempo basal (B), no tempo do choque (Choque 0), sessenta minutos depois do choque (Choque 60), imediatamente depois da ressuscitação com hidroxietilamido 6% (130/0. 4) (R0), uma hora (R60) e duas horas (R120) depois ressuscitação. Os pontos de avaliação da reanimação por fluidos foram determinados pelo retorno aos valores basais iniciais de VPP e IVDFVD. A análise estatística dos dados foi baseada em ANOVA para medidas repetidas seguidos pelo teste de Bonferroni (P<0.05%). RESULTADOS: O volume e tempo para ressuscitação foram maiores no grupo III do que no grupo II (Grupo III = 1305±331ml e Grupo II = 965±245ml; p<0.05 e Grupo III = 24.8± 4.7min e Grupo II = 8.8 ± 1.3 min, p<0.01, respectivamente). Todos os parâmetros estáticos e dinâmicos, bem como os biomarcadores de oxigenação tecidual foram afetados pelo choque hemorrágico e quase todos os parâmetros foram totalmente restaurados após a reanimação em ambos os grupos. CONCLUSÃO: Neste estudo em modelo de choque hemorrágico, a reanimação guiada pelo VPP utilizou menor quantidade de fluido e menor quantidade de tempo do que quando guiado por IVDFVD derivado de cateter de artéria pulmonar.
INTRODUCTION: Different hemodynamic parameters, including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally-induced hemorrhagic shock. METHODS: 26 anesthetized and mechanically ventilated pigs were allocated into control (Group-I), PPV (Group-II) and RVEDVI (Group- III). Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40mmHg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, sixty minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), one hour and two hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on ANOVA for repeated measures followed by the Bonferroni test (P<0.05). RESULTS: Volume and time to resuscitation were higher in Group-III than in Group-II (Group-III = 1305±331ml and Group-II = 965±245ml; p<0.05 and Group-IIII = 24.8±4.7min and Group-II = 8.8±1.3 min, p<0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. CONCLUSION: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.
Assuntos
Animais , Cuidados Críticos , Monitorização Fisiológica , Choque Hemorrágico , SuínosRESUMO
Cysteine plays structural roles in proteins and can also participate in electron transfer reactions, when some structural folds provide appropriatedenvironments for stabilization of its sulfhydryl group in the anionic form, called thiolate (RS−). In contrast, sulfhydryl group of free cysteine has arelatively high pKa (8,5) and as a consequence is relatively inert for redox reaction in physiological conditions. Thiolate is considerable morepowerful as nucleophilic agent than its protonated form, therefore, reactive cysteine are present mainly in its anionic form in proteins. In this review,we describe several processes in which reactive cysteine in proteins take part, showing a high degree of redox chemistry versatility.
Assuntos
Masculino , Feminino , Humanos , Antioxidantes/classificação , Cisteína/metabolismo , Peróxidos/classificaçãoRESUMO
Thioredoxin reductase 1 (Trr1) from Saccharomyces cerevisiae is a member of the family of pyridine nucleotide-disulfide oxidoreductases capable of reducing the redox-active disulfide bond of the cytosolic thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2). NADPH, Trr1 and Trx1 (or Trx2) comprise the thioredoxin system, which is involved in several biological processes, including the reduction of disulfide bonds and response to oxidative stress. Recombinant Trr1 was expressed in Escherichia coli as a His6-tagged fusion protein and purified by nickel-affinity chromatography. The protein was crystallized using the hanging-drop vapour-diffusion method in the presence of PEG 3000 as precipitant after treatment with hydrogen peroxide. X-ray diffraction data were collected to a maximum resolution of 2.4 A using a synchrotron-radiation source. The crystal belongs to the centred monoclinic space group C2, with unit-cell parameters a = 127.97, b = 135.41, c = 75.81 A, beta = 89.95 degrees. The crystal structure was solved by molecular-replacement methods and structure refinement is in progress.
Assuntos
Proteínas de Saccharomyces cerevisiae/química , Tiorredoxina Dissulfeto Redutase/química , Clonagem Molecular , Cristalização/métodos , Histidina , Polietilenoglicóis , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão , Volatilização , Difração de Raios XRESUMO
Glutaredoxins are small (9-12 kDa) heat-stable proteins that are highly conserved throughout evolution; the glutaredoxin active site (Cys-Pro-Tyr-Cys) is conserved in most species. Five glutaredoxin genes have been identified in Saccharomyces cerevisiae; however, Grx2 is responsible for the majority of oxidoreductase activity in the cell, suggesting that its primary function may be the detoxification of mixed disulfides generated by reactive oxygen species (ROS). Recombinant Grx2 was expressed in Escherichia coli as a 6xHis-tagged fusion protein and purified by nickel-affinity chromatography. Prior to crystallization trials, the enzyme was submitted to various treatments with reducing agents and peroxides. Crystals suitable for X-ray diffraction experiments were obtained from untreated protein and protein oxidized with t-butyl hydroperoxide (10 mM). Complete data sets were collected to resolutions 2.15 and 2.05 A for untreated and oxidized Grx2, respectively, using a synchrotron-radiation source. The crystals belong to space group P4(1)2(1)2, with similar unit-cell parameters.
Assuntos
Oxirredutases/química , Proteínas de Saccharomyces cerevisiae/química , Clonagem Molecular , Cristalização/métodos , Escherichia coli/genética , Glutarredoxinas , Histidina/química , Oxirredução , Difração de Raios X , terc-Butil HidroperóxidoRESUMO
Propöe sondar as representaçöes presentes nos discursos médicos-sanitaristas e da Imprensa Operária formulados no período de 1890-1930, momento de crescimento urbano e que coincide, com a ampliaçäo da presença médica na capital paulista. Resgatou-se o discurso médico e da imprensa operária construída no início do século XX até a década de 1930, tentando perceber as convergências entre os discursos, aproximaçöes e tensöes e todo o processo de incorporaçäo que ambos os discursos fizeram um do outro.(AU)