Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Determinação de teor de biodieseis de algodão e pinhão manso em misturas com diesel usando espectroscopia no infravermelho médio e quadrados mínimos parciais

Biodiesel is a renewable fuel derived from vegetable oils or animal fats, which can be a total or partial substitute for diesel. Since 2005, this fuel was introduced in the Brazilian energy matrix through Law 11.097 that determines the percentage of biodiesel added to diesel oil as well as monitoring the insertion of this fuel in market. The National Agency of Petroleum, Natural Gas and Biofuels (ANP) establish the obligation of adding 7% (v/v) of biodiesel to diesel commercialized in the country, making crucial the analytical control of this content. Therefore, in this study were developed and validated methodologies based on the use of Mid Infrared Spectroscopy (MIR) and Multivariate Calibration by Partial Least Squares (PLS) to quantify the methyl and ethyl biodiesels content of cotton and jatropha in binary blends with diesel at concentration range from 1.00 to 30.00% (v/v), since this is the range specified in standard ABNT NBR 15568. The biodiesels were produced from two routes, using ethanol or methanol, and evaluated according to the parameters: oxidative stability, water content, kinematic viscosity and density, presenting results according to ANP Resolution No. 45/2014. The built PLS models were validated on the basis of ASTM E1655-05 for Infrared Spectroscopy and Multivariate Calibration and ABNT NBR 15568, with satisfactory results due to RMSEP (Root Mean Square Error of Prediction) values below 0.08% (<0.1%), correlation coefficients (R) above 0.9997 and the absence of systematic error (bias). Therefore, the methodologies developed can be a promising alternative in the quality control of this fuel.

Valor em relacionamentos: sua influência na competitividade e desenvolvimento do Arranjo Produtivo Local de fruticultura em Itacoatiara/Amazonas

Tese apresentada ao Programa de Doutorado em Administração da Universidade Municipal de São Caetano do Sul para a obtenção do título de Doutor em Administração

Crenças normativas e comportamentais e suas influências na intenção de adoção de um sistema de informação: um estudo na área de compras da UFPA

The study aims to identify the factors that influence the behavior intention to adopt an academic Information System (SIE), in an environment of mandatory use, applied in the procurement process at the Federal University of Pará (UFPA). For this, it was used a model of innovation adoption and technology acceptance (TAM), focused in attitudes and intentions regarding the behavior intention. The research was conducted a quantitative survey, through survey in a sample of 96 administrative staff of the researched institution. For data analysis, it was used structural equation modeling (SEM), using the partial least squares method (Partial Least Square PLS-PM). As to results, the constructs attitude and subjective norms were confirmed as strong predictors of behavioral intention in a pre-adoption stage. Despite the use of SIE is required, the perceived voluntariness also predicts the behavior intention. Regarding attitude, classical variables of TAM, like as ease of use and perceived usefulness, appear as the main influence of attitude towards the system. It is hoped that the results of this study may provide subsidies for more efficient management of the process of implementing systems and information technologies, particularly in public universities

Aceitação e uso de ambiente virtual de aprendizagem no contexto de um curso de capacitação para servidores públicos

This study aimed to examine how students perceives the factors that may influence them to attend a training course offered in the distance virtual learning environment (VLE) of the National School of Public Administration (ENAP). Thus, as theoretical basis it was used the Unified Theory of Acceptance and Use of Technology (UTAUT), the result of an integration of eight previous models which aimed to explain the same phenomenon (acceptance/use of information technology). The research approach was a quantitative and qualitative. To achieve the study objectives were made five semi-structured interviews and an online questionnaire (websurvey) in a valid sample of 101 public employees scattered throughout the country. The technique used to the analysis of quantitative data was the structural equation modeling (SEM), by the method of Partial Least Square Path Modeling (PLS-PM). To qualitative data was the thematic content analysis. Among the results, it was found that, in the context of public service, the degree whose the individual believes that the use of an AVA will help its performance at work (performance expectancy) is a factor to its intended use and also influence its use. Among the results, it was found that the belief which the public employee has in the use of a VLE as a way to improve the performance of his work (performance expectation) was determinant for its intended use that, in turn, influenced their use. It was confirmed that, under the voluntary use of technology, the general opinion of the student s social circle (social influence) has no effect on their intention to use the VLE. The effort expectancy and facilitating conditions were not directly related to the intended use and use, respectively. However, emerged from the students speeches that the opinions of their coworkers, the ease of manipulate the VLE, the flexibility of time and place of the distance learning program and the presence of a tutor are important to their intentions to do a distance learning program. With the results, it is expected that the managers of the distance learning program of ENAP turn their efforts to reduce the impact of the causes of non-use by those unwilling to adopt voluntarily the e-learning, and enhance the potentialities of distance learning for those who are already users

Crenças normativas e comportamentais e suas influências na intenção de adoção de um sistema de informação: um estudo na área de compras da UFPA

The study aims to identify the factors that influence the behavior intention to adopt an academic Information System (SIE), in an environment of mandatory use, applied in the procurement process at the Federal University of Pará (UFPA). For this, it was used a model of innovation adoption and technology acceptance (TAM), focused in attitudes and intentions regarding the behavior intention. The research was conducted a quantitative survey, through survey in a sample of 96 administrative staff of the researched institution. For data analysis, it was used structural equation modeling (SEM), using the partial least squares method (Partial Least Square PLS-PM). As to results, the constructs attitude and subjective norms were confirmed as strong predictors of behavioral intention in a pre-adoption stage. Despite the use of SIE is required, the perceived voluntariness also predicts the behavior intention. Regarding attitude, classical variables of TAM, like as ease of use and perceived usefulness, appear as the main influence of attitude towards the system. It is hoped that the results of this study may provide subsidies for more efficient management of the process of implementing systems and information technologies, particularly in public universities

Aceitação e uso de ambiente virtual de aprendizagem no contexto de um curso de capacitação para servidores públicos

This study aimed to examine how students perceives the factors that may influence them to attend a training course offered in the distance virtual learning environment (VLE) of the National School of Public Administration (ENAP). Thus, as theoretical basis it was used the Unified Theory of Acceptance and Use of Technology (UTAUT), the result of an integration of eight previous models which aimed to explain the same phenomenon (acceptance/use of information technology). The research approach was a quantitative and qualitative. To achieve the study objectives were made five semi-structured interviews and an online questionnaire (websurvey) in a valid sample of 101 public employees scattered throughout the country. The technique used to the analysis of quantitative data was the structural equation modeling (SEM), by the method of Partial Least Square Path Modeling (PLS-PM). To qualitative data was the thematic content analysis. Among the results, it was found that, in the context of public service, the degree whose the individual believes that the use of an AVA will help its performance at work (performance expectancy) is a factor to its intended use and also influence its use. Among the results, it was found that the belief which the public employee has in the use of a VLE as a way to improve the performance of his work (performance expectation) was determinant for its intended use that, in turn, influenced their use. It was confirmed that, under the voluntary use of technology, the general opinion of the student s social circle (social influence) has no effect on their intention to use the VLE. The effort expectancy and facilitating conditions were not directly related to the intended use and use, respectively. However, emerged from the students speeches that the opinions of their coworkers, the ease of manipulate the VLE, the flexibility of time and place of the distance learning program and the presence of a tutor are important to their intentions to do a distance learning program. With the results, it is expected that the managers of the distance learning program of ENAP turn their efforts to reduce the impact of the causes of non-use by those unwilling to adopt voluntarily the e-learning, and enhance the potentialities of distance learning for those who are already users

Aplicação de modelos de equações estruturais no estudo da eficácia de Sistemas de Gestão de Desempenho

Para fazer face às exigências da sociedade, as organizações têm a necessidade de desenvolver esforços de modo a aumentar a sua performance, através de práticas de gestão estratégica de recursos humanos. Nesta dissertação iremos aprofundar o estudo do modelo proposto por Marr (2009) para explicar a Cultura Orientada para o Desempenho e demonstrar os efeitos que a cultura tem nos Sistemas de Gestão de Desempenho, utilizando os Modelos de Equações Estruturais, através da análise de respostas obtidas sobre 325 colaboradores de empresas portuguesas do sector público e privado. Desta análise resultou a confirmação das quatro dimensões latentes de Cultura Organizacional propostas pelo autor, através da Análise Factorial Confirmatória, revelando também a sua importância e contributos diferenciados no Sistema de Gestão de Desempenho de uma organização. De um modo geral, verificou-se que as dimensões da Cultura contribuem de forma positiva para o aumento da eficácia de um Sistema de Gestão de Desempenho, alinhado com o modelo conceptual proposto e enfatizando a importância de se estudar as dimensões de Cultura e de Sistemas de Gestão de Desempenho de forma simultânea.

Modelagem do desempenho ambiental dos projetos de exploração e produção aplicando equações estruturais

A legislação ambiental e os principais agentes que se relacionam com a empresa se constituem em fatores exógenos que não podem ser negligenciados ao formular-se e avaliar-se a política ambiental corporativa. As influências exógenas e seus efeitos sobre a gestão ambiental e o gerenciamento de projetos de exploração e produção (E&P) e, por essa via, sobre o desempenho ambiental, foram objetos de estudo desta tese. Embora o desempenho ambiental seja um assunto relevante, a pesquisa sobre esse tema ainda é escassa. Tal carência desponta ainda mais acentuada quando se aborda o desempenho ambiental de projetos na indústria de petróleo e gás. O principal objetivo deste estudo foi avaliar a relação entre a legislação ambiental vigente, as ações de órgãos reguladores, fornecedores, empresas terceirizadas e comunidades locais e o desempenho ambiental dos projetos de E&P na indústria de petróleo e gás e, também, analisar os efeitos do sistema de gestão ambiental e o gerenciamento dos projetos sobre tal desempenho. Na fase abdutiva, foi conduzido um estudo de caso com abordagem qualitativa em uma grande empresa brasileira do setor de petróleo e gás, na fase dedutiva, foi realizada uma pesquisa survey explanatória de corte transversal com abordagem quantitativa, incluindo 113 projetos de E&P de cinco unidades executoras da empresa. Foi formulado um modelo conceitual, com cinco construtos e sete hipóteses de pesquisa, representativo dos efeitos de fatores externos sobre o desempenho ambiental dos projetos de E&P. Os dados foram tratados aplicando a Análise Fatorial Exploratória e a Modelagem de Equações Estruturais com aplicação dos softwares IBM® SPSS® Statistics 20.0 e IBM® SPSS® Amos 18.0. O modelo de equações estruturais foi reespecificado e estimado utilizando o método de Máxima Verossimilhança e o procedimento bootstrap com 2000 reamostragens, até alcançar adequados valores dos índices de ajustamento. O modelo mostrou boa aderência às evidências empíricas, representando uma teoria explicativa dos fatores que influenciam o desempenho ambiental dos projetos de E&P na empresa estudada. As estatísticas descritivas apontaram adequado desempenho dos projetos de E&P com relação aos efluentes descartados, volume de água reutilizada, redução de resíduos e práticas de reciclagem. Identificou-se que projetos de maior porte alcançam melhor desempenho ambiental em relação aos de menor tamanho. Não foram achadas diferenças significativas entre os desempenhos de projetos executados por unidades operacionais distintas. Os resultados da modelagem indicaram que nem a legislação ambiental, nem os agentes externos exercem influência significativa sobre a sistemática da gestão dos projetos de E&P. Os agentes externos atuam sobre a gestão ambiental da empresa exercitando capacidades colaborativas, obstrutivas e propositivas. A legislação ambiental é percebida como entrave ao desenvolvimento dos projetos ao longo de seu ciclo de vida, principalmente, pelas deficiências dos órgãos ambientais. Identificou-se que o sistema de gestão ambiental influencia diretamente o Programa de Desenvolvimento e Execução de Projetos de E&P, que, por sua vez, provoca efeitos diretos e indiretos sobre o desempenho ambiental. Finalmente, comprovou-se que o Sistema de Gestão Ambiental da empresa é determinante para o desempenho ambiental dos projetos de E&P, tanto pelos seus efeitos diretos, como pelos indiretos, estes últimos mediados pela sistemática de gestão dos projetos de E&P

TESE = Governança e Satisfação: um estudo nos APLs Têxtil e de Confecções e Moveleiro do Grande ABC

Tese apresentada ao Programa de Pós-Graduação em Administração da Universidade Municipal de São Caetano do Sul como requisito para a obtenção do título de Doutora em Administração.

Questionário de cooperação organizacional: Estudos diferenciais

O objectivo do presente trabalho foi verificar as diferenças entre grupos, quanto à cooperação, numa amostra de 300 funcionários de 70 Câmaras Municipais, nas variáveis tempo de trabalho, função desempenhada, área de trabalho, idade, sexo e habilitações académicas. Utilizámos o Questionário de Cooperação Organizacional. Não observámos diferenças significativas nas variáveis tempo de serviço, área de trabalho, idade, sexo e habilitações académicas em nenhum dos três factores do QCO (cooperação configurada por regulamentações formais, cooperação decorrente da interdependência de indivíduos únicos articulados entre si, e cooperação através da orientação para a sociedade dos contributos singulares). Na variável função desempenhada, não houve diferenças significativas no primeiro nem no terceiro factores. No segundo factor, observámos uma diferença significativa entre administrativos (que referem que se coopera pouco) e ocupantes de cargos de direcção e chefia (que referem que se coopera moderadamente). As variáveis estudadas não são, em geral, pertinentes para a diferenciação dos processos de cooperação. /ABSTRACT: The aim of this dissertation was to test the differences between groups, concerning cooperation, on a random sample with 300 workers from 70 municipalities, focusing on the variables working time, task, working department, age, gender and qualifications. We used the Questionnaire on Organizational Cooperation. No significant differences in the variables working time, working department, age, gender, and qualifications in any of the three dimensions of the QOC (cooperation shaped by formal regulations; cooperation arising from the interdependence of unique individuals articulated with one another; cooperation towards society, arising from the individual action) were found. We found no significant differences in the variable task, neither in the first nor in the third factor. ln the second factor, we observed a significant difference between clerks (who state that cooperation is little) and workers in leading and management positions (who state that cooperation is moderate). The variables that were studied are not generally relevant to the differentiation of the cooperation processes.

Equações de predição para estimar o valor de energia metabolizável do milho para frangos de corte.

2016