Spin-Transfer-Torque Nano-Oscillators: Fabrication, Characterization and Dynamics

NASA Astrophysics Data System (ADS)

Costa, Jose Diogo Teixeira Barbosa

Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que permitiu concluir que os momentos magneticos descompensados estao aleatoriamente distribuidos em volume. Usando baixas concentracoes de agua, foi possivel crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanoparticulas de maguemite e magnetite acontece apos incorporacao de ioes de Fe2+ e Fe3+ seguidos de tratamento basico e termico. Estes sistemas apresentam propriedades magneticas tipicas de nanoparticulas superparamagneticas sem interaccoes dipolares. As propriedades magneticas dependem criticamente da existencia de grupos isocianato livres, que actuarao como pontos de nucleacao. None

Structural and Magnetic Studies on Iron Oxide Nanoparticles in Hybrid Matrices =

NASA Astrophysics Data System (ADS)

Silva, Nuno Joao de Oliveira

Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que permitiu concluir que os momentos magneticos descompensados estao aleatoriamente distribuidos em volume. Usando baixas concentracoes de agua, foi possivel crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanoparticulas de maguemite e magnetite acontece apos incorporacao de ioes de Fe2+ e Fe3+ seguidos de tratamento basico e termico. Estes sistemas apresentam propriedades magneticas tipicas de nanoparticulas superparamagneticas sem interaccoes dipolares. As propriedades magneticas dependem criticamente da existencia de grupos isocianato livres, que actuarao como pontos de nucleacao. None

PNAUM: integrated approach to Pharmaceutical Services, Science, Technology and Innovation.

PubMed

Gadelha, Carlos Augusto Grabois; Costa, Karen Sarmento; Nascimento, José Miguel do; Soeiro, Orlando Mário; Mengue, Sotero Serrate; Motta, Márcia Luz da; Carvalho, Antônio Carlos Campos de

2016-12-01

This paper describes the development process of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines) based on an integrated approach to pharmaceutical services, science, technology and innovation. It starts by contextualizing health and development in Brazil and features elements of the National Policy for Science, Technology and Innovation in Health in Brazil and the National Policy for Pharmaceutical Services. On presenting pharmaceutical policy guidelines, it stresses the lack of nationwide data. This survey, commissioned by the Brazilian Ministry of Health, has two components: household survey and evaluation of pharmaceutical services in primary care. The findings point to perspectives that represent, besides the enhancement of public policy for pharmaceutical services and public health, results of government action aimed at developing the economic and industrial health care complex to improve the health conditions of the Brazilian population. RESUMO O artigo apresenta o processo de construção da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamento a partir de uma concepção integradora da Assistência Farmacêutica, Ciência, Tecnologia e Inovação. Inicia-se contextualizando a saúde e o desenvolvimento no País e apresenta elementos da Política Nacional de Ciência Tecnologia e Inovação em Saúde no Brasil e da Política Nacional de Assistência Farmacêutica. Ao apresentar as diretrizes das Políticas Farmacêuticas, destaca-se a carência de dados de abrangência nacional. A presente pesquisa, encomendada pelo Ministério da Saúde, foi estruturada em dois componentes: inquérito domiciliar e avaliação dos serviços de assistência farmacêutica na atenção básica. As perspectivas dos resultados representam, além do incremento das políticas públicas farmacêuticas e de saúde pública, resultados de ações governamentais voltadas ao desenvolvimento do complexo econômico-industrial da saúde, visando a melhoria das condições de saúde da população brasileira.

Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry

PubMed Central

Keiflin, Ronald; Janak, Patricia H.

2015-01-01

Summary Midbrain dopamine (DA) neurons are proposed to signal reward prediction error (RPE), a fundamental parameter in associative learning models. This RPE hypothesis provides a compelling theoretical framework for understanding DA function in reward learning and addiction. New studies support a causal role for DA-mediated RPE activity in promoting learning about natural reward; however, this question has not been explicitly tested in the context of drug addiction. In this review, we integrate theoretical models with experimental findings on the activity of DA systems, and on the causal role of specific neuronal projections and cell types, to provide a circuit-based framework for probing DA-RPE function in addiction. By examining error-encoding DA neurons in the neural network in which they are embedded, hypotheses regarding circuit-level adaptations that possibly contribute to pathological error-signaling and addiction can be formulated and tested. PMID:26494275

Abundância química de simbióticas na direção do bojo galáctico

NASA Astrophysics Data System (ADS)

Luna, G. J. M.; Costa, R. D. D.

2003-08-01

O estudo da distribuição de metalicidades de gigantes K no Bojo indica um largo intervalo com valores entre 0.1 a 10 vezes o valor solar. As razões elementais Ca/Fe, Si/Fe, Mg/Fe são típicas de estrelas do halo, apontando para um processo rápido de enriquecimento, via estrelas masssivas (SN's tipo II). No entanto, este cenário não combina com os resultados derivados de nebulosas planetárias do bojo tais como os de Ratag et al. (1992, A&A,255,270), Cuisinier et al.(2000, A&A,353, 543), Escudero e Costa (2001, A&A,380, 300),que obtêm abundâncias análogas às do disco. Neste cenário, o estudo de estrelas simbióticas possibilita uma abordagem particularmente apropriada para o problema das abundâncias químicas de estrelas de massa intermediária em estágios avançados da evoluçao estelar. Apresentamos aqui os resultados da determinacão das abundâncias do grupo do CNO numa extensa amostra de simbióticas do bojo. Aliás, com a disponibilidade de espectros no visível determinamos também abundâncias de Ar, Ne, S e He, fundamentais para analisar os processos de enriquecimento químico ocorridos ao longo da evolução estelar, bem como a evolução química do meio interestelar. Com os espectros UV do satelite IUE obtivemos abundâncias de C, necessárias no estudo da evolução dos sistemas. As relaçoes C/N-O/N mostram que o material nebular é produto do vento da componente gigante e não dos eventos de nova que às vezes acontecem nestes sistemas, como foi mostrado por Nussbaumer et al (1988,A&A,198,179). As abundâncias de Ar, S, Ne e O são compativeis com resultados de fontes no disco e bojo, seguindo o gradiente proposto por muitos autores na literatura a partir de diferentes objetos como cefeidas, nebulosas planetárias e anãs G. (CAPES,FAPESP,CNPq)

Raven surgical robot training in preparation for da vinci.

PubMed

Glassman, Deanna; White, Lee; Lewis, Andrew; King, Hawkeye; Clarke, Alicia; Glassman, Thomas; Comstock, Bryan; Hannaford, Blake; Lendvay, Thomas S

2014-01-01

The rapid adoption of robotic assisted surgery challenges the pace at which adequate robotic training can occur due to access limitations to the da Vinci robot. Thirty medical students completed a randomized controlled trial evaluating whether the Raven robot could be used as an alternative training tool for the Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci robot. Two groups, one trained on the da Vinci and one trained on the Raven, were tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS block transfer proficiency training there was no statistically significant difference between path length (p=0.39) and economy of motion scores (p=0.06) between the two groups, but those trained on the da Vinci did have faster task times (p=0.01). These results provide evidence for the value of using the Raven robot for training prior to using the da Vinci surgical system for similar tasks.

Domoic acid excretion in dungeness crabs, razor clams and mussels.

PubMed

Schultz, Irvin R; Skillman, Ann; Woodruff, Dana

2008-07-01

Domoic acid (DA) is a neurotoxic amino acid produced by several marine algal species of the Pseudo-nitzschia (PN) genus. We studied the elimination of DA from hemolymph after intravascular (IV) injection in razor clams (Siliqua patula), mussels (Mytilus edulis) and Dungeness crabs (Cancer magister). Crabs were also injected with two other organic acids, dichloroacetic acid (DCAA) and kainic acid (KA). For IV dosing, hemolymph was repetitively sampled and DA concentrations measured by HPLC-UV. Toxicokinetic analysis of DA in crabs suggested most of the injected dose remained within hemolymph compartment with little extravascular distribution. This observation is in sharp contrast to results obtained from clams and mussels which exhibited similarly large apparent volumes of distribution despite large differences in overall clearance. These findings suggest fundamentally different storage and elimination processes are occurring for DA between bivalves and crabs.

Providing Meaningful Learning for Students of the Sixth Grade of Middle School: a Study on the Moon Phases. (Breton Title: Propiciando Aprendizagem Significativa Para Alunos do Sexto Ano do Ensino Fundamental: um Estudo sobre as Fases da Lua.) Propiciando el Aprendizaje Significativo Para Alumnos del Sexto Nivel de la Educación General Básica: un Estudio sobre Las Fases de la Luna

NASA Astrophysics Data System (ADS)

Darroz, Luiz Marcelo; Samudio Pérez, Carlos Ariel; da Rosa, Cleci Werner; Heineck, Renato

2012-07-01

We relate in this article a didactic experience studying the moon phases with a group of middle school students of a private school of the municipality of Passo Fundo, RS. Based on David Ausubel's Meaningful Learning Theory, we have sought to develop a proposal following a didactic model which simulates the phases of the Moon, as based on the previous conceptions of the students. The signs of learning were evidenced by means of memory registries of the activity. From the obtained results we believe that the proposal achieved its goals, since the students were able to identify, differentiate and transfer the phenomenon of the moon phases to new contexts. Thus, it is concluded that a methodology focused on a meaningful content for the students is fundamental to the construction and genuine grasping of what is being learned. Neste artigo, relata-se uma experiência didática de estudo das fases da Lua com uma turma do 6° ano do Ensino Fundamental, de uma escola privada do município de Passo Fundo, RS. Tendo como fundamentação teórica a Teoria da Aprendizagem Significativa de David Ausubel, buscou-se desenvolver a proposta a partir de um modelo didático que simula as fases da Lua e com base nas concepções prévias dos estudantes. Os indícios da aprendizagem foram constatados através de registros de memórias da atividade. Pelos resultados apresentados, acredita-se que a proposta alcançou seus objetivos, uma vez que os estudantes conseguiram identificar, diferenciar e transferir o fenômeno das fases da Lua para novos contextos. Assim, conclui-se que uma metodologia com enfoque em um conteúdo significativo ao estudante é fundamental para a construção e compreensão genuína do que está sendo aprendido. En este artículo se relata una experiencia didáctica de estudio de las fases de la Luna con una clase de 6º año de la educación general básica de una escuela privada del municipio de Passo Fundo, RS. Teniendo como fundamentación teórica la Teoría del Aprendizaje Significativo de David Ausubel, se buscó desenvolver la propuesta a partir de un modelo didáctico que simula las Fases de la Luna, usando como base las concepciones previas de los estudiantes. Los indicios del aprendizaje fueron verificados a través de registros de memorias de la actividad. Por los resultados obtenidos creemos que la propuesta alcanzó sus objetivos, una vez que los estudiantes consiguieron identificar y transferir el fenómeno de las fases de la Luna para nuevos contextos. Así, se concluye que una metodología con enfoque en un contenido significativo para el estudiante es fundamental para la construcción y comprensión genuina de lo que está siendo aprendido.

Estudo em microondas do aprisionamento e precipitação de elétrons em explosões solares

NASA Astrophysics Data System (ADS)

Rosal, A. C.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação rápida e intensa do brilho que ocorre nas chamadas regiões ativas da atmosfera, constituídas por um plasma magnetizado com intensa indução magnética. Os modelos de explosões solares atuais, discutidos na literatura, apresentam características de aprisionamento e precipitação de elétrons em ambientes magnéticos simplificados. Neste trabalho, nos propusemos a separar a emissão dos elétrons aprisionados da emissão dos elétrons em precipitação apenas a partir da emissão em microondas, melhorando portanto o controle sobre o conjunto de parâmetros inferidos. A emissão em microondas da população em precipitação é bastante fraca e portanto da nossa base de dados de 130 explosões observadas pelo Rádio Polarímetro de Nobeyama, em sete freqüências, apenas para 32 foi possível separar as duas componentes de emissão com uma boa razão sinal/ruído. A partir de estudos das escalas de tempo das emissões devidas à variação gradual da emissão no aprisionamento e da variação rápida da emissão dos elétrons em precipitação foi possível obter a separação utilizando um filtro temporal nas emissões resultantes. Em nossa análise destas explosões estudamos os espectros girossincrotrônicos da emissão gradual, a qual associamos provir do topo dos arcos magnéticos e da emissão de variação rápida associada aos elétrons em precipitação. Estes espectros foram calculados e dos quais inferimos que a indução magnética efetiva do topo e dos pés foi em média, Btopo = 236 G e Bpés = 577 G, inferidas das freqüências de pico dos espectros em ntopo = 11,8 GHz e npés = 14,6 GHz com leve anisotropia (pequeno alargamento espectral). O índice espectral da distribuição não-térmica de elétrons d, inferido do índice espectral de fótons da emissão em regime opticamente fino, foi de dtopo = 3,3 e dpés = 3,9. Estes parâmetros são típicos da maioria das análises realizadas em ambiente único de emissão e a relação dos índices espectrais, dpés > dtopo prioriza as interpretações com difusão em ângulo de passo devida a colisões Coulombianas. Nesta difusão o déficit de elétrons energéticos na precipitação seria uma conseqüência natural da dependência em e-3/2 das colisões elétron-próton (onde e é a energia dos elétrons).

Exploring the Neither in João Pedro Rodrigues and João Rui Guerra Da Mata's "A ultima vez que vi Macau"

ERIC Educational Resources Information Center

ten Haaf, Rachel

2017-01-01

Torn between two colonial powers, Macau has long existed as a peripheral region in Lusophone studies. This current study explores João Pedro Rodrigues and João Rui Guerra da Mata's 2012 film "A ultima vez que vi Macau". With a focus on a contemporary Macau that seeks to resolve its fundamental duality through investigation of gender,…

Effective Universal Coverage of Diabetes Mellitus Type 2 in Chile.

PubMed

Guerrero-Núñez, Sara; Valenzuela-Suazo, Sandra; Cid-Henríquez, Patricia

2017-04-06

determine the prevalence of Effective Universal Coverage of Diabetes Mellitus Type 2 in Chile and its relation with the variables: Health Care Coverage of Diabetes Mellitus Type 2; Average of diabetics with metabolic control in 2011-2013; Mortality Rate for Diabetes Mellitus; and Percentage of nurses participating in the Cardiovascular Health Program. cross-sectional descriptive study with ecological components that uses documentary sources of the Ministry of Health. It was established that there is correlation between the Universal Effective Coverage of Diabetes Mellitus Type 2 and the independent variables; it was applied the Pearson Coefficient, being significant at the 0.05 level. in Chile Universal Health Care Coverage of Diabetes Mellitus Type 2 (HbA1c<7% estimated population) is less than 20%; this is related with Mortality Rate for Diabetes Mellitus and Percentage of nurses participating in the Cardiovascular Health Program, being significant at the 0.01 level. effective prevalence of Universal Health Coverage of Diabetes Mellitus Type 2 is low, even though some regions stand out in this research and in the metabolic control of patients who participate in health control program; its relation with percentage of nurses participating in the Cardiovascular Health Program represents a challenge and an opportunity for the health system. determinar a prevalência de Cobertura Universal Efetiva da Diabetes Mellitus tipo 2 em Chile e sua relação com as variáveis; Cobertura da Diabetes Mellitus tipo 2, Média de diabéticos com controle metabólico em 2011-2013, Taxa de Mortalidade por Diabetes Mellitus e Percentagem de participação de enfermeiras no Programa de Saúde Cardiovascular. estudo descritivo transversal com componentes ecológicos, utilizando fontes documentais do Ministério da Saúde. Foi estabelecida correlação entre Cobertura Universal Efetiva da Diabetes Mellitus tipo 2 e as variáveis independentes, aplicando o Coeficiente de Pearson, sendo significante ao 0,05. no Chile a Cobertura Universal Efetiva da Diabetes Mellitus tipo 2 (HbA1c<7% em população estimada) é menor que 20%. Esta se relaciona com uma Taxa de Mortalidade por Diabetes Mellitus e Percentagem de participação de enfermeiras no Programa de Saúde Cardiovascular, que ademais é significativa ao 0,01. a prevalência de Cobertura Universal Efetiva da Diabetes Mellitus tipo 2 é baixa, mesmo quando algumas regiões se destacam nas pesquisas e no controle metabólico de pacientes assistentes ao controle. Sua relação com a Percentagem de participação de enfermeiras no Programa de Saúde Cardiovascular se constitui em um desafio e oportunidade em saúde. determinar la prevalencia de la Cobertura Universal Efectiva de la diabetes mellitus tipo 2 en Chile y su relación con las variables: Cobertura de Diabetes Mellitus tipo 2, Promedio de diabéticos con control metabólico en 2011-2013, Tasa de Mortalidad por Diabetes Mellitus y Porcentaje de participación de enfermeros en el Programa de Salud Cardiovascular. estudio descriptivo transversal con componentes ecológicos, utilizando fuentes documentales del Ministerio de Salud. Se estableció que existe correlación entre la Cobertura Universal Efectiva de la Diabetes Mellitus tipo 2 y las variables independientes, aplicando el Coeficiente de Pearson, siendo significativa al nivel 0,05. en Chile la Cobertura Universal Efectiva de Diabetes Mellitus tipo 2 (HbA1c<7% en población estimada) es menor que 20%; esta se relaciona con la Tasa de Mortalidad por Diabetes Mellitus y con el Porcentaje de participación de enfermeras en el Programa de Salud Cardiovascular, que es significativa al nivel 0,01. la prevalencia de Cobertura Universal Efectiva de la Diabetes Mellitus tipo 2 es baja; sin embargo algunas regiones se destacan en la cobertura y en el control metabólico de pacientes que participan del control de salud. La relación de la cobertura con el porcentaje de participación de enfermeras en el Programa de Salud Cardiovascular es un desafío y una oportunidad en salud.

Improving Ecological Forecasting: Data Assimilation Enhances the Ecological Forecast Horizon of a Complex Food Web

NASA Astrophysics Data System (ADS)

Massoud, E. C.; Huisman, J.; Benincà, E.; Bouten, W.; Vrugt, J. A.

2017-12-01

Species abundances in ecological communities can display chaotic non-equilibrium dynamics. A characteristic feature of chaotic systems is that long-term prediction of the system's trajectory is fundamentally impossible. How then should we make predictions for complex multi-species communities? We explore data assimilation (DA) with the Ensemble Kalman Filter (EnKF) to fuse a two-predator-two-prey model with abundance data from a long term experiment of a plankton community which displays chaotic dynamics. The results show that DA improves substantially the predictability and ecological forecast horizon of complex community dynamics. In addition, we show that DA helps provide guidance on measurement design, for instance on defining the frequency of observations. The study presented here is highly innovative, because DA methods at the current stage are almost unknown in ecology.

A distribuição de velocidades na linha de visada em galáxias barradas vistas de face

NASA Astrophysics Data System (ADS)

Gadotti, D. A.; de Souza, R. E.

2003-08-01

Com o objetivo de realizar um estudo cinemático da componente vertical de barras em galáxias, obtivemos espectros de fenda longa de alta razão S/N ao longo dos eixos maior e menor de 14 galáxias barradas vistas de face, nos telescópios de 1.52m do ESO em La Silla, Chile, e de 2.3m do Steward Observatory em Kitt Peak, Arizona. Estes dados nos permitiram determinar a distribuição de velocidades das estrelas ao longo do eixo vertical das barras e discos destes sistemas, tanto no centro como em pontos que distam cerca de 5 e 20 segundos de arco do núcleo, correspondendo a distâncias de cerca de 0.7 e 2.8 kpc, respectivamente. Desta forma, a variação radial da distribuição de velocidades também pôde ser avaliada. Este tipo de análise tem raros exemplos na literatura por ser caro em termos de tempo de telescópio. Entretanto, é de fácil justificativa, considerando que traz novas informações que podem ser utilizadas para aperfeiçoar modelos teóricos acerca da formação e evolução de galáxias. Um algoritmo por nós desenvolvido foi utilizado para obter as distribuições de velocidades como Gaussianas generalizadas (polinômios de Gauss-Hermite), o que traz um ingrediente a mais neste tipo de estudo que, tradicionalmente, se utiliza de Gaussianas puras, uma hipótese nem sempre razoável. Apresentaremos os resultados deste trabalho, que incluem um diagnóstico para a identificação de barras recém formadas, e testes para o modelo isotérmico de discos. Mostraremos que: (i) a escolha das estrelas padrão em velocidade, e dos parâmetros da Gaussiana, deve ser muito bem justificada já que tem influência significativa nos resultados; (ii) muitas galáxias apresentam uma depressão na dispersão de velocidades na região central, que pode estar associada a um disco interno; e (iii) a dispersão de velocidades é constante ao longo da barra, nos eixos maior e menor, mas cai substancialmente quando se passa da barra para o disco.

A Utilização da Astronomia como Tema Interdisciplinar e Aplicações de Objetos de Aprendizagem

NASA Astrophysics Data System (ADS)

da Silva, L. A.; Voelzke, M. R.

2008-09-01

Este trabalho visa analisar a possibilidade de relacionar conteúdos aplicados no ensino fundamental e médio de forma interdisciplinar por intermédio da astronomia, com a intervenção de objetos de aprendizagem que possam integrar as disciplinas e a utilização de recursos tecnológicos. Em uma pesquisa prévia com 20 professores de uma escola estadual situada na cidade de Guarulhos foi observado que apenas 25% dos professores utilizam algum recurso tecnológico para o desenvolvimento de conteúdos pertinentes à sua disciplina, tais como sites e softwares educativos, sendo que a maioria absoluta continua ensinando apenas com livros didáticos. A maior parte dos professores apresenta dificuldades em trabalhar sua disciplina de forma interdisciplinar, ou seja, 75% dos professores preferem aplicar os conteúdos seguindo uma hierarquia linear de tópicos, evitando a discussão de temas que de alguma forma estão relacionados. A astronomia pode vir à fascinar o ser humano e despertar sua curiosidade promovendo um maior interesse no aprendizado, podendo favorecer análises interdisciplinares de forma lógica e objetiva, desta forma colocar a astronomia como tema motivador interdisciplinar, pode ser relevante no que se refere ao distanciamento da fragmentação dos conteúdos. No Estado de São Paulo, a implantação da proposta curricular no ensino fundamental e médio mostra claramente a inserção da astronomia na maior parte das séries, principalmente na 6ª série em que todo o bimestre se fala de astronomia.

Connecting nitrogen deposition and ecosystem services

EPA Science Inventory

There are tremendous human health and well-being consequences of nitrogen release to the atmosphere, land and water. The effects on human health are related to the fundamental ecosystem services providing clean air and water for human consumption. Among the highest available da...

Projeto educação em ciências com observatórios virtuais: a participação da Escola Moppe no período 2000-2003

NASA Astrophysics Data System (ADS)

Wuensche, C. A.; Gavioli, E.; Oliveira, A. L. P. R. S.; da Silva, C.; Cardoso, H. P.; Estácio, S.

2003-08-01

O projeto Educação em Ciências com Observatórios Virtuais foi concebido pelo Instituto Astronômico e Geofísico da USP, agregando diversas instituições de ensino e pesquisa no país para desenvolver competências diversas na educação fundamental, média e superior utilizando a astronomia como ferramenta multidisciplinar. Este trabalho descreve a participação da MOPPE, escola-piloto do INPE no projeto, no período de 2000-2003. Serão apresentadas 1) a criação de um clube de ciências (1999 a 2001) cujo tema foi a colonização de Marte e 2) a ementa de astronomia trabalhada com as 7a. e 8a. séries do ensino fundamental. A proposta do projeto Colonizando Marte foi estudar diversos aspectos de uma missão interplanetária e construir experiementos que permitissem quantificar esses aspectos. Os resultados obtidos incluiram apresentações nas SBPC Jovem em 2000 e 2001. Discutiremos também as ementas de astronomia trabalhadas desde 2001 e o envolvimento dos alunos com atividades ligadas a astronomia, fora da aula de ciências. A inclusão de astronomia no currículo das últimas séries motivou a participação de mais alunos culminando com a conquista de duas medalhas para alunos da 7a. série na Olimpiada Brasileira de Astronomia em 2002. Houve também um aumento no número de participantes na OBA 2003 e nos projetos de astronomia mais elaborados nas Feira de Ciências de 2001 e 2002. Destacamos em 2003 a inclusão da MOPPE no projeto TIE - Telescopes in Education - da NASA, que utiliza o telescópio do Observatório de Mount Wilson (EUA) para observações remotas em projetos pedagógicos para o ensino de astronomia.

Visual degradation in Leonardo da Vinci's iconic self-portrait: A nanoscale study

NASA Astrophysics Data System (ADS)

Conte, A. Mosca; Pulci, O.; Misiti, M. C.; Lojewska, J.; Teodonio, L.; Violante, C.; Missori, M.

2014-06-01

The discoloration of ancient paper, due to the development of oxidized groups acting as chromophores in its chief component, cellulose, is responsible for severe visual degradation in ancient artifacts. By adopting a non-destructive approach based on the combination of optical reflectance measurements and time-dependent density functional theory ab-initio calculations, we describe and quantify the chromophores affecting Leonardo da Vinci's iconic self-portrait. Their relative concentrations are very similar to those measured in modern and ancient samples aged in humid environments. This analysis quantifies the present level of optical degradation of the Leonardo da Vinci's self-portrait which, compared with future measurements, will assess its degradation rate. This is a fundamental information in order to plan appropriate conservation strategies.

Current Perspectives on Pathobiology of the Ductus Arteriosus

PubMed Central

Stoller, Jason Z.; DeMauro, Sara B.; Dagle, John M.; Reese, Jeff

2012-01-01

The ductus arteriosus (DA) shunts blood away from the lungs during fetal life, but at birth this shunt is no longer needed and the vessel rapidly constricts. Postnatal persistence of the DA, patent ductus arteriosus (PDA), is predominantly a detrimental condition for preterm infants but is simultaneously a condition required to maintain systemic blood flow for infants born with certain severe congenital heart defects. Although PDA in preterm infants is associated with significant morbidities, there is controversy regarding whether PDA is truly causative. Despite advances in our understanding of the pathobiology of PDA, the optimal treatment strategy for PDA in preterm infants is unclear. Here we review recent studies that have continued to elucidate the fundamental mechanisms of DA development and pathogenesis. PMID:23519783

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

PubMed Central

Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

2016-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2009-06-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.

Factors associated with poor sleep quality in women with cancer.

PubMed

Mansano-Schlosser, Thalyta Cristina; Ceolim, Maria Filomena

2017-03-02

to analyze the factors associated with poor sleep quality, its characteristics and components in women with breast cancer prior to surgery for removing the tumor and throughout the follow-up. longitudinal study in a teaching hospital, with a sample of 102 women. The following were used: a questionnaire for sociodemographic and clinical characterization, the Pittsburgh Sleep Quality Index; the Beck Depression Inventory; and the Herth Hope Scale. Data collection covered from prior to the surgery for removal of the tumor (T0) to T1, on average 3.2 months; T2, on average 6.1 months; and T3, on average 12.4 months. Descriptive statistics and the Generalized Estimating Equations model were used. depression and pain contributed to the increase in the score of the Pittsburgh Sleep Quality Index, and hope, to the reduction of the score - independently - throughout follow-up. Sleep disturbances were the component with the highest score throughout follow-up. the presence of depression and pain, prior to the surgery, contributed to the increase in the global score of the Pittsburgh Sleep Quality Index, which indicates worse quality of sleep throughout follow-up; greater hope, in its turn, influenced the reduction of the score of the Pittsburgh Sleep Quality Index. analizar los factores asociados a la mala calidad del sueño, sus características y componentes en mujeres con cáncer de mama, antes de la cirugía de retirada del tumor y a lo largo del seguimiento. estudio longitudinal, en hospital universitario con muestra de 102 mujeres. Fueron utilizados: un cuestionario de caracterización sociodemográfica y clínica; el Índice de Calidad del Sueño de Pittsburgh; el Inventario de Depresión de Beck; y la Escala de Esperanza de Herth. La recolección comprendió los momentos: antes de la cirugía de retirada del tumor (T0), en (T1) en promedio 3,2 meses, en (T2) en promedio 6,1 meses y en (T3) en promedio 12,4 meses. Se utilizó estadística descriptiva y el modelo de Ecuaciones de Estimación Generalizada. la depresión y el dolor contribuyeron para el aumento del puntaje del Índice de Calidad del Sueño de Pittsburgh y la esperanza para la reducción del puntaje, de manera independiente, a lo largo del seguimiento. Los trastornos del sueño fueron el componente con puntuación más elevada, a lo largo del seguimiento. la presencia de la depresión y del dolor, previos a la cirugía, contribuyeron para el aumento del puntaje global del Índice de Calidad del Sueño de Pittsburgh, lo que indica peor calidad del sueño, a lo largo del seguimiento y, la mayor esperanza, a su vez, influenció en la reducción del puntaje del Índice de Calidad del Sueño de Pittsburgh. analisar os fatores associados à má qualidade do sono, suas características e componentes em mulheres com câncer de mama antes da cirurgia de retirada do tumor e ao longo do seguimento. estudo longitudinal, em hospital universitário com amostra de 102 mulheres. Foram utilizados: questionário de caracterização sociodemográfica e clínica, Índice de Qualidade do Sono de Pittsburgh; Inventário de Depressão de Beck; Escala de Esperança de Herth. Coleta compreendeu antes da cirurgia de retirada do tumor (T0) em T1, em média 3,2 meses; T2, em média 6,1 meses; T3, em média 12,4 meses. Utilizou-se estatística descritiva e o modelo de Equações de Estimação Generalizada. a depressão e a dor contribuíram para o aumento do escore do Índice de Qualidade de Sono de Pittsburgh, e a esperança, para a redução do escore, de maneira independente, ao longo do seguimento. Os transtornos do sono foram o componente com pontuação mais elevada, ao longo do seguimento. a presença de depressão e de dor, previamente à cirurgia, contribuiu para o aumento do escore global do Índice de Qualidade do Sono de Pittsburgh, o que indica pior qualidade do sono, ao longo do seguimento e, a maior esperança, por sua vez, influenciou na redução do escore do Índice de Qualidade do Sono de Pittsburgh.

Biaxial seismic behaviour of reinforced concrete columns =

NASA Astrophysics Data System (ADS)

Rodrigues, Hugo Filipe Pinheiro

A analise dos efeitos dos sismos mostra que a investigacao em engenharia sismica deve dar especial atencao a avaliacao da vulnerabilidade das construcoes existentes, frequentemente desprovidas de adequada resistencia sismica tal como acontece em edificios de betao armado (BA) de muitas cidades em paises do sul da Europa, entre os quais Portugal. Sendo os pilares elementos estruturais fundamentais na resistencia sismica dos edificios, deve ser dada especial atencao a sua resposta sob acoes ciclicas. Acresce que o sismo e um tipo de acao cujos efeitos nos edificios exige a consideracao de duas componentes horizontais, o que tem exigencias mais severas nos pilares comparativamente a acao unidirecional. Assim, esta tese centra-se na avaliacao da resposta estrutural de pilares de betao armado sujeitos a acoes ciclicas horizontais biaxiais, em tres linhas principais. Em primeiro lugar desenvolveu-se uma campanha de ensaios para o estudo do comportamento ciclico uniaxial e biaxial de pilares de betao armado com esforco axial constante. Para tal foram construidas quatro series de pilares retangulares de betao armado (24 no total) com diferentes caracteristicas geometricas e quantidades de armadura longitudinal, tendo os pilares sido ensaiados para diferentes historias de carga. Os resultados experimentais obtidos sao analisados e discutidos dando particular atencao a evolucao do dano, a degradacao de rigidez e resistencia com o aumento das exigencias de deformacao, a energia dissipada, ao amortecimento viscoso equivalente; por fim e proposto um indice de dano para pilares solicitados biaxialmente. De seguida foram aplicadas diferentes estrategias de modelacao nao-linear para a representacao do comportamento biaxial dos pilares ensaiados, considerando nao-linearidade distribuida ao longo dos elementos ou concentrada nas extremidades dos mesmos. Os resultados obtidos com as varias estrategias de modelacao demonstraram representar adequadamente a resposta em termos das curvas envolventes forca-deslocamento, mas foram encontradas algumas dificuldades na representacao da degradacao de resistencia e na evolucao da energia dissipada. Por fim, e proposto um modelo global para a representacao do comportamento nao-linear em flexao de elementos de betao armado sujeitos a acoes biaxiais ciclicas. Este modelo tem por base um modelo uniaxial conhecido, combinado com uma funcao de interacao desenvolvida com base no modelo de Bouc- Wen. Esta funcao de interacao foi calibrada com recurso a tecnicas de otimizacao e usando resultados de uma serie de analises numericas com um modelo refinado. E ainda demonstrada a capacidade do modelo simplificado em reproduzir os resultados experimentais de ensaios biaxiais de pilares.

Astronomia Motivadora no Ensino Fundamental

NASA Astrophysics Data System (ADS)

Melo, J.; Voelzke, M. R.

2008-09-01

O objetivo principal deste trabalho é procurar desenvolver o interesse dos alunos pelas ciências através da Astronomia. Uma pesquisa com perguntas sobre Astronomia foi realizada junto a 161 alunos do Ensino Fundamental, com o intuito de descobrir conhecimentos prévios dos alunos sobre o assunto. Constatou-se, por exemplo, que 29,3% da 6ª série responderam corretamente o que é eclipse, 30,0% da 8ª série acertaram o que a Astronomia estuda, enquanto 42,3% dos alunos da 5ª série souberam definir o Sol. Pretende-se ampliar as turmas participantes e trabalhar, principalmente de forma prática com: dimensões e escalas no Sistema Solar, construção de luneta, questões como dia e noite, estações do ano e eclipses. Busca-se abordar, também, outros conteúdos de Física tais como a óptica na construção da luneta, e a mecânica no trabalho com escalas e medidas, e ao utilizar uma luminária para representar o Sol na questão do eclipse, e de outras disciplinas como a Matemática na transformação de unidades, regras de três; Artes na modelagem ou desenho dos planetas; a própria História com relação à busca pela origem do universo, e a Informática que possibilita a busca mais rápida por informações, além de permitir simulações e visualizações de imagens importantes. Acredita-se que a Astronomia é importante no processo ensino aprendizagem, pois permite a discussão de temas curiosos como, por exemplo, a origem do universo, viagens espaciais a existência ou não de vida em outros planetas, além de temas atuais como as novas tecnologias.

Development of a Novel Biosensor Using Cationic Antimicrobial Peptide and Nickel Phthalocyanine Ultrathin Films for Electrochemical Detection of Dopamine

PubMed Central

Zampa, Maysa F.; Araújo, Inês Maria de S.; dos Santos Júnior, José Ribeiro; Zucolotto, Valtencir; Leite, José Roberto de S. A.; Eiras, Carla

2012-01-01

The antimicrobial peptide dermaseptin 01 (DS 01), from the skin secretion of Phyllomedusa hypochondrialis frogs, was immobilized in nanostructured layered films in conjunction with nickel tetrasulfonated phthalocyanines (NiTsPc), widely used in electronic devices, using layer-by-layer technique. The films were used as a biosensor to detect the presence of dopamine (DA), a neurotransmitter associated with diseases such as Alzheimer's and Parkinson's, with detection limits in the order of 10−6 mol L−1. The use of DS 01 in LbL film generated selectivity in the detection of DA despite the presence of ascorbic acid found in biological fluids. This work is the first to report that the antimicrobial peptide and NiTsPc LbL film exhibits electroanalytical activity to DA oxidation. The selectivity in the detection of DA is a fundamental aspect for the development of electrochemical sensors with potential applications in the biomedical and pharmaceutical industries. PMID:22287966

Estudo de soluções locais e cosmológicas em teorias do tipo tensor-escalar

NASA Astrophysics Data System (ADS)

Silva E Costa, S.

2003-08-01

Teorias do tipo tensor-escalar são a mais simples extensão possí vel da Relatividade Geral. Nessas teorias, cujo modelo padrão é a teoria de Brans-Dicke, a curvatura do espaço-tempo, descrita por componentes tensoriais, aparece acoplada a um campo escalar que, de certo modo, representa uma variação na constante de acoplamento da gravitação. Tais teorias apresentam soluções locais e cosmológicas que, em determinados limites, recaem nas apresentadas pela Relatividade Geral, mas que em outros limites trazem novidades, tais como conseqüências observacionais da evolução de flutuações primordiais distintas daquelas previstas pela Relatividade Geral (ver, por ex., Nagata et al., PRD 66, p. 103510 (2002)). Graças a esta possibilidade de trazer à luz novidades em relação à gravitação, teorias do tipo tensor-escalar podem ser vistas como um interessante campo alternativo de pesquisas para soluções dos problemas de massa faltante (ou escura) e/ou energia escura. Seguindo tal linha, este trabalho, ainda em sua fase inicial, apresenta soluções gerais de teorias do tipo tensor-escalar para diversas situações, verificando-se em que consiste a divergência dessas soluções dos casos tradicionais possí veis na Relatividade Geral. Como exemplos das soluções aqui apresentadas pode-se destacar uma expressão geral para diferentes soluções cosmológicas englobando diferentes tipos de matéria (representados por diferentes equações de estado), e a expressão para uma solução local representando um buraco negro com rotação, similar à solução de Kerr da Relatividade Geral. Por fim, é importante ressaltar que, embora aqui apresentem-se poucos resultados novos, na literatura sobre o assunto a maior parte das soluções apresentadas limita-se a uns poucos casos especí ficos, tal como soluções cosmológicas apenas com curvatura nula, e que mesmo as soluções disponí veis são, em geral, pouco divulgadas e, portanto, pouco conhecidas, e é tal situação que este trabalho busca, em parte, reverter.

Dopamine suppresses neuronal activity of Helisoma B5 neurons via a D2-like receptor, activating PLC and K channels.

PubMed

Zhong, L R; Artinian, L; Rehder, V

2013-01-03

Dopamine (DA) plays fundamental roles as a neurotransmitter and neuromodulator in the central nervous system. How DA modulates the electrical excitability of individual neurons to elicit various behaviors is of great interest in many systems. The buccal ganglion of the freshwater pond snail Helisoma trivolvis contains the neuronal circuitry for feeding and DA is known to modulate the feeding motor program in Helisoma. The buccal neuron B5 participates in the control of gut contractile activity and is surrounded by dopaminergic processes, which are expected to release DA. In order to study whether DA modulates the electrical activity of individual B5 neurons, we performed experiments on physically isolated B5 neurons in culture and on B5 neurons within the buccal ganglion in situ. We report that DA application elicited a strong hyperpolarization in both conditions and turned the electrical activity from a spontaneously firing state to an electrically silent state. Using the cell culture system, we demonstrated that the strong hyperpolarization was inhibited by the D2 receptor antagonist sulpiride and the phospholipase C (PLC) inhibitor U73122, indicating that DA affected the membrane potential of B5 neurons through the activation of a D2-like receptor and PLC. Further studies revealed that the DA-induced hyperpolarization was inhibited by the K channel blockers 4-aminopyridine and tetraethylammonium, suggesting that K channels might serve as the ultimate target of DA signaling. Through its modulatory effect on the electrical activity of B5 neurons, the release of DA in vivo may contribute to a neuronal output that results in a variable feeding motor program. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Structure of an extracellular giant hemoglobin of the gutless beard worm Oligobrachia mashikoi

PubMed Central

Numoto, Nobutaka; Nakagawa, Taro; Kita, Akiko; Sasayama, Yuichi; Fukumori, Yoshihiro; Miki, Kunio

2005-01-01

Mouthless and gutless marine animals, pogonophorans and vestimentiferans, obtain their nutrition solely from their symbiotic chemoautotrophic sulfur-oxidizing bacteria. These animals have sulfide-binding 400-kDa and/or 3,500-kDa Hb, which transports oxygen and sulfide simultaneously. The symbiotic bacteria are supplied with sulfide by Hb of the host animal and use it to provide carbon compounds. Here, we report the crystal structure of a 400-kDa Hb from pogonophoran Oligobrachia mashikoi at 2.85-Å resolution. The structure is hollow-spherical, composed of a total of 24 globins as a dimer of dodecamer. This dodecameric assemblage would be a fundamental structural unit of both 400-kDa and 3,500-kDa Hbs. The structure of the mercury derivative used for phasing provides insights into the sulfide-binding mechanism. The mercury compounds bound to all free Cys residues that have been expected as sulfide-binding sites. Some of the free Cys residues are surrounded by Phe aromatic rings, and mercury atoms come into contact with these residues in the derivative structure. It is strongly suggested that sulfur atoms bound to these sites could be stabilized by aromatic-electrostatic interactions by the surrounding Phe residues. PMID:16204001

Molecular Determinants Fundamental to Axon Regeneration after SCI

DTIC Science & Technology

2012-06-01

gray arrow) and a 130kDa N-terminal processed neurocan fragment (black arrow) in chABC treated samples (Asher et. al., 2000). Zebrafish brain tissue...PTPRSREV: GTG TGT GTG CTG ATG AAG GTC GC (EXON 9). 275 bp product expected. We have also designed a forward primer in exon 6 with negative results

Quadrupole Ion Mass Spectrometer for Masses of 2 to 50 Da

NASA Technical Reports Server (NTRS)

Helms, William; Griffin, Timothy P.; Ottens, Andrew; Harrison, Willard

2005-01-01

A customized quadrupole ion-trap mass spectrometer (QITMS) has been built to satisfy a need for a compact, rugged instrument for measuring small concentrations of hydrogen, helium, oxygen, and argon in a nitrogen atmosphere. This QITMS can also be used to perform quantitative analyses of other gases within its molecular-mass range, which is 2 to 50 daltons (Da). (More precisely, it can be used to perform quantitative analysis of gases that, when ionized, are characterized by m/Z ratios between 2 and 50, where m is the mass of an ion in daltons and Z is the number of fundamental electric charges on the ion.

The Isolation and Characterization of Glycosylated Phosphoproteins from Herring Fish Bones*

PubMed Central

Zhou, Hai-Yan; Salih, Erdjan; Glimcher, Melvin J.

2010-01-01

Past studies of bone extracellular matrix phosphoproteins such as osteopontin and bone sialoprotein have yielded important biological information regarding their role in calcification and the regulation of cellular activity. Most of these studies have been limited to proteins extracted from mammalian and avian vertebrates and nonvertebrates. The present work describes the isolation and purification of two major highly glycosylated and phosphorylated extracellular matrix proteins of 70 and 22 kDa from herring fish bones. The 70-kDa phosphoprotein has some characteristics of osteopontin with respect to amino acid composition and susceptibility to thrombin cleavage. Unlike osteopontin, however, it was found to contain high levels of sialic acid similar to bone sialoprotein. The 22-kDa protein has very different properties such as very high content of phosphoserine (∼270 Ser(P) residues/1000 amino acid residues), Ala, and Asx residues. The N-terminal amino acid sequence analysis of both the 70-kDa (NPIMA(M)ETTS(M)DSKVNPLL) and the 22-kDa (NQDMAMEASSDPEAA) fish phosphoproteins indicate that these unique amino acid sequences are unlike any published in protein databases. An enzyme-linked immunosorbent assay revealed that the 70-kDa phosphoprotein was present principally in bone and in calcified scales, whereas the 22-kDa phosphoprotein was detected only in bone. Immunohistological analysis revealed diffusely positive immunostaining for both the 70- and 22-kDa phosphoproteins throughout the matrix of the bone. Overall, this work adds additional support to the concept that the mechanism of biological calcification has common evolutionary and fundamental bases throughout vertebrate species. PMID:20833721

Nucleus accumbens dopamine and the regulation of effort in food-seeking behavior: implications for studies of natural motivation, psychiatry, and drug abuse.

PubMed

Salamone, J D; Correa, M; Mingote, S; Weber, S M

2003-04-01

For several decades, it has been suggested that dopamine (DA), especially in nucleus accumbens, mediates the primary reinforcing characteristics of natural stimuli such as food, as well as drugs of abuse. Yet, several fundamental aspects of primary food reinforcement, motivation, and appetite are left intact after interference with accumbens DA transmission. Recent studies have shown that accumbens DA is involved in responsiveness to conditioned stimuli and activational aspects of motivation. In concurrent choice tasks, accumbens DA depletions cause animals to reallocate their choice behavior in the direction of instrumental behaviors that involve less effort. Also, an emerging body of evidence has demonstrated that the effects of accumbens DA depletions on instrumental food-seeking behavior can vary greatly depending upon the task. For example, some schedules of reinforcement are insensitive to the effects of DA depletions, whereas others are highly sensitive (e.g., large fixed ratios). Accumbens DA depletions slow the rate of operant responding, blunt the rate-facilitating effects of moderate-sized ratios, and enhance the rate-suppressing effects of very large ratios (i.e., produce ratio strain). Accumbens DA may be important for enabling rats to overcome behavioral constraints, such as work-related response costs, and may be critical for the behavioral organization and conditioning processes that enable animals to engage in vigorous responses, such as barrier climbing, or to emit large numbers of responses in ratio schedules in the absence of primary reinforcement. The involvement of accumbens DA in activational aspects of motivation has implications for energy-related disorders in psychiatry, as well as aspects of drug-seeking behavior.

Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

PubMed

Laviolette, Steven R

2007-07-01

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

Protein profiling of water and alkali soluble cottonseed protein isolates.

PubMed

He, Zhongqi; Zhang, Dunhua; Cao, Heping

2018-06-18

Currently, there is only limited knowledge on the protein types and structures of the cottonseed proteins. In this work, water-soluble cottonseed proteins (CSPw) and alkali-soluble cottonseed proteins (CSPa) were sequentially extracted from defatted cottonseed meal. Proteins of the two fractions were separated by 4-20% gradient polyacrylamide gel electrophoresis (SDS-PAGE); There were 7 and 12 polypeptide bands on SDS-PAGE of CSPa and CSPw, respectively. These individual bands were then excised from the gel and subjected to mass spectrometric analysis. There were total 70 polypeptides identified from the proteins of the two cottonseed preparations, with molecular weights ranging from 10 to 381 kDa. While many proteins or their fragments were found in multiple bands, 18 proteins appeared only in one SDS-PAGE band (6 in CSPa, 12 in CSPw). Putative functions of these proteins include storage, transcription/translation, synthesis, energy metabolism, antimicrobial activity, and embryogenesis. Among the most abundant are legumin A (58 kDa), legumin B (59 kDa), vicilin C72 (70 kDa), vicilin GC72-A (71 kDa), and vicilin-like antimicrobial peptides (62 kDa). This work enriched the fundamental knowledge on cottonseed protein composition, and would help in better understanding of the functional and physicochemical properties of cottonseed protein and for enhancing its biotechnological utilization.

A Introdução de Astronomia Básica para Estudantes de 5 e 6 Séries do Ensino Fundamental

NASA Astrophysics Data System (ADS)

Gonzaga, E. P.; Voelzke, M. R.

2008-09-01

Com intuito de despertar o interesse pelo estudo da astronomia, desenvolveu-se entre 2003 e 2006 no Centro Educacional do Serviço Social da Indústria situado no município de Mauá, São Paulo, um trabalho com duração de 12 meses para turmas de 11 e 12 anos, sendo três turmas por período (2003 / 2004, 2004 / 2005 e 2005 / 2006). O trabalho realizado, objetivando a introdução da astronomia básica com observações de constelações e das fases da Lua, permitindo estender-se a outros corpos celestes, iniciou-se com visita ao planetário Mundo Estelar, localizado no Ipiranga, São Paulo levantou-se a questão da importância do estudo da astronomia e foi lançado aos estudantes um trabalho de observação, com a proposta de localizar as constelações e compreender as fases da Lua, para o registro de tais observações, foram distribuídos mapas celestes, pastas, planilhas de anotações com lacunas para, constelações, fases da Lua e relatos, onde os estudantes acrescentaram pesquisas e relatórios. Os resultados dos 346 estudantes foram que 86,7% (300) concluíram a etapa de observação, destes 300 estudantes 43,3% (130) pesquisaram sobre as constelações e 19,0% (57) localizaram até quatro constelações. Dos 346 estudantes, 44,2% (153) registraram as fases da Lua equivocadamente e 10,4% (36) anexaram reportagens sobre astronomia. Conclui-se que os estudantes se dividiram em pesquisadores, sendo os estudantes que registraram e anexaram informações e, os observadores que preencheram as planilhas de observações, além de desenvolverem habilidades e competências relacionadas ao estudo da astronomia.

Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets.

PubMed

Fuxe, Kjell; Agnati, Luigi F; Marcoli, Manuela; Borroto-Escuela, Dasiel O

2015-12-01

Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor-receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural-glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron-glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin-angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.

Examining Testlet Effects in the TestDaF Listening Section: A Testlet Response Theory Modeling Approach

ERIC Educational Resources Information Center

Eckes, Thomas

2014-01-01

Testlets are subsets of test items that are based on the same stimulus and are administered together. Tests that contain testlets are in widespread use in language testing, but they also share a fundamental problem: Items within a testlet are locally dependent with possibly adverse consequences for test score interpretation and use. Building on…

Validation of an instrument for evaluating health care services to ostomized people.

PubMed

Moraes, Juliano Teixeira; Amaral, Carlos Faria Santos; Borges, Eline Lima; Ribeiro, Mauro Souza; Guimarães, Eliete Albano Azevedo

2016-12-08

to develop and validate an array of analysis and judgment for the evaluation of Health Care Services of people with stomas. cross-sectional study in 28 health facilities in the state of Minas Gerais. A descriptive analysis of the instrument and a study of its psychometric properties were performed. We used the Delphi technique for the validation of content and appearance. A psychometric analysis was carried out through the study of the reliability and validity of the measures obtained with the instrument. it was possible to construct an array analysis and judgment with 16 components (with scores from zero to five) grouped according to size and structure and process considered essential to evaluate the service. The results achieved in the reliability for structure and process, through the Cronbach alpha coefficient (α = 0.771 and α = 0.809, respectively), and the validity of content and construct demonstrated good internal consistency and satisfactory validity. An exploratory factor analysis indicated the item "main activity performed in the unit" as a limitation of the scale. the study provides a new tool for the evaluation of structure and process of Health Care Services of a Person with a stoma. desenvolver e validar uma matriz de análise e julgamento para a avaliação de Serviços de Atenção à Saúde da Pessoa Estomizada. estudo seccional em 28 unidades de saúde do estado de Minas Gerais. Foi realizada uma análise descritiva do instrumento e um estudo das suas propriedades psicométricas. Para a validação de conteúdo e de aparência foi utilizada a técnica Delphi. A análise psicométrica foi realizada por meio do estudo da confiabilidade e validade das medidas obtidas com o instrumento. foi possível construir uma matriz de análise e julgamento com 16 componentes (pontuados com escores de zero a cinco) agrupados de acordo com as dimensões estrutura e processo considerados fundamentais para a avaliação do serviço. Os resultados alcançados para a confiabilidade para estrutura e processo, por meio do Coeficiente alfa de Cronbach (α = 0,771 e α = 0,809 respectivamente), e validades de conteúdo e de construto, demonstraram boa consistência interna e satisfatória validade. A análise fatorial exploratória apontou o item "principal atividade realizada na unidade" como limitação da escala. o estudo disponibiliza nova ferramenta para a avaliação de estrutura e processo do Serviço de Atenção à Saúde da Pessoa Ostomizada. desarrollar y validar una matriz de análisis y juzgamiento para la evaluación de Servicios de Atención a la Salud de la Persona Ostomizada. estudio seccional en 28 unidades de salud del estado de Minas Gerais. Fue realizado un análisis descriptivo del instrumento y un estudio de sus propiedades psicométricas. Para la validación de contenido y de apariencia fue utilizada la técnica Delphi. El análisis psicométrico fue realizada por medio del estudio de la confiabilidad y validez de las medidas obtenidas con el instrumento. fue posible construir una matriz de análisis y juzgamiento con 16 componentes (evaluados con puntajes de cero a cinco) agrupados de acuerdo con las dimensiones estructura y proceso considerados fundamentales para la evaluación del servicio. Los resultados alcanzados para la confiabilidad para estructura y proceso, por medio del Coeficiente Alfa de Cronbach (α = 0,771 y α = 0,809 respectivamente), y validez de contenido y de constructo, demostraron buena consistencia interna y satisfactoria validez. El análisis factorial exploratória apuntó el ítem "principal actividad realizada en la unidad" como limitación de la escala. el estudio suministra una nueva herramienta para la evaluación de estructura y proceso del Servicio de Atención a la Salud de la Persona Ostomizada.

SCFSAP controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana

PubMed Central

Wang, Zhibiao; Li, Na; Jiang, Shan; Gonzalez, Nathalie; Huang, Xiahe; Wang, Yingchun; Inzé, Dirk; Li, Yunhai

2016-01-01

Control of organ size by cell proliferation and growth is a fundamental process, but the mechanisms that determine the final size of organs are largely elusive in plants. We have previously revealed that the ubiquitin receptor DA1 regulates organ size by repressing cell proliferation in Arabidopsis. Here we report that a mutant allele of STERILE APETALA (SAP) suppresses the da1-1 mutant phenotype. We show that SAP is an F-box protein that forms part of a SKP1/Cullin/F-box E3 ubiquitin ligase complex and controls organ size by promoting the proliferation of meristemoid cells. Genetic analyses suggest that SAP may act in the same pathway with PEAPOD1 and PEAPOD2, which are negative regulators of meristemoid proliferation, to control organ size, but does so independently of DA1. Further results reveal that SAP physically associates with PEAPOD1 and PEAPOD2, and targets them for degradation. These findings define a molecular mechanism by which SAP and PEAPOD control organ size. PMID:27048938

SCF(SAP) controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana.

PubMed

Wang, Zhibiao; Li, Na; Jiang, Shan; Gonzalez, Nathalie; Huang, Xiahe; Wang, Yingchun; Inzé, Dirk; Li, Yunhai

2016-04-06

Control of organ size by cell proliferation and growth is a fundamental process, but the mechanisms that determine the final size of organs are largely elusive in plants. We have previously revealed that the ubiquitin receptor DA1 regulates organ size by repressing cell proliferation in Arabidopsis. Here we report that a mutant allele of STERILE APETALA (SAP) suppresses the da1-1 mutant phenotype. We show that SAP is an F-box protein that forms part of a SKP1/Cullin/F-box E3 ubiquitin ligase complex and controls organ size by promoting the proliferation of meristemoid cells. Genetic analyses suggest that SAP may act in the same pathway with PEAPOD1 and PEAPOD2, which are negative regulators of meristemoid proliferation, to control organ size, but does so independently of DA1. Further results reveal that SAP physically associates with PEAPOD1 and PEAPOD2, and targets them for degradation. These findings define a molecular mechanism by which SAP and PEAPOD control organ size.

To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity.

PubMed

Beeler, Jeff A; Mourra, Devry

2018-01-01

Five years ago, we introduced the thrift hypothesis of dopamine (DA), suggesting that the primary role of DA in adaptive behavior is regulating behavioral energy expenditure to match the prevailing economic conditions of the environment. Here we elaborate that hypothesis with several new ideas. First, we introduce the concept of affordability, suggesting that costs must necessarily be evaluated with respect to the availability of resources to the organism, which computes a value not only for the potential reward opportunity, but also the value of resources expended. Placing both costs and benefits within the context of the larger economy in which the animal is functioning requires consideration of the different timescales against which to compute resource availability, or average reward rate. Appropriate windows of computation for tracking resources requires corresponding neural substrates that operate on these different timescales. In discussing temporal patterns of DA signaling, we focus on a neglected form of DA plasticity and adaptation, changes in the physical substrate of the DA system itself, such as up- and down-regulation of receptors or release probability. We argue that changes in the DA substrate itself fundamentally alter its computational function, which we propose mediates adaptations to longer temporal horizons and economic conditions. In developing our hypothesis, we focus on DA D2 receptors (D2R), arguing that D2R implements a form of "cost control" in response to the environmental economy, serving as the "brain's comptroller". We propose that the balance between the direct and indirect pathway, regulated by relative expression of D1 and D2 DA receptors, implements affordability. Finally, as we review data, we discuss limitations in current approaches that impede fully investigating the proposed hypothesis and highlight alternative, more semi-naturalistic strategies more conducive to neuroeconomic investigations on the role of DA in adaptive behavior.

To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity

PubMed Central

Beeler, Jeff A.; Mourra, Devry

2018-01-01

Five years ago, we introduced the thrift hypothesis of dopamine (DA), suggesting that the primary role of DA in adaptive behavior is regulating behavioral energy expenditure to match the prevailing economic conditions of the environment. Here we elaborate that hypothesis with several new ideas. First, we introduce the concept of affordability, suggesting that costs must necessarily be evaluated with respect to the availability of resources to the organism, which computes a value not only for the potential reward opportunity, but also the value of resources expended. Placing both costs and benefits within the context of the larger economy in which the animal is functioning requires consideration of the different timescales against which to compute resource availability, or average reward rate. Appropriate windows of computation for tracking resources requires corresponding neural substrates that operate on these different timescales. In discussing temporal patterns of DA signaling, we focus on a neglected form of DA plasticity and adaptation, changes in the physical substrate of the DA system itself, such as up- and down-regulation of receptors or release probability. We argue that changes in the DA substrate itself fundamentally alter its computational function, which we propose mediates adaptations to longer temporal horizons and economic conditions. In developing our hypothesis, we focus on DA D2 receptors (D2R), arguing that D2R implements a form of “cost control” in response to the environmental economy, serving as the “brain’s comptroller”. We propose that the balance between the direct and indirect pathway, regulated by relative expression of D1 and D2 DA receptors, implements affordability. Finally, as we review data, we discuss limitations in current approaches that impede fully investigating the proposed hypothesis and highlight alternative, more semi-naturalistic strategies more conducive to neuroeconomic investigations on the role of DA in adaptive behavior. PMID:29487508

Next Generation Workload Management System For Big Data on Heterogeneous Distributed Computing

NASA Astrophysics Data System (ADS)

Klimentov, A.; Buncic, P.; De, K.; Jha, S.; Maeno, T.; Mount, R.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Porter, R. J.; Read, K. F.; Vaniachine, A.; Wells, J. C.; Wenaus, T.

2015-05-01

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS and ALICE are the largest collaborations ever assembled in the sciences and are at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, both experiments rely on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System (WMS) for managing the workflow for all data processing on hundreds of data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. The scale is demonstrated by the following numbers: PanDA manages O(102) sites, O(105) cores, O(108) jobs per year, O(103) users, and ATLAS data volume is O(1017) bytes. In 2013 we started an ambitious program to expand PanDA to all available computing resources, including opportunistic use of commercial and academic clouds and Leadership Computing Facilities (LCF). The project titled ‘Next Generation Workload Management and Analysis System for Big Data’ (BigPanDA) is funded by DOE ASCR and HEP. Extending PanDA to clouds and LCF presents new challenges in managing heterogeneity and supporting workflow. The BigPanDA project is underway to setup and tailor PanDA at the Oak Ridge Leadership Computing Facility (OLCF) and at the National Research Center "Kurchatov Institute" together with ALICE distributed computing and ORNL computing professionals. Our approach to integration of HPC platforms at the OLCF and elsewhere is to reuse, as much as possible, existing components of the PanDA system. We will present our current accomplishments with running the PanDA WMS at OLCF and other supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications.

Distinct Acoustic Features and Glottal Changes Define Two Modes of Singing in Peking Opera.

PubMed

Li, Gelin; Li, Haiqing; Hou, Qian; Jiang, Zhen

2018-04-06

We aimed to delineate the acoustic characteristics of the Laodan and Qingyi role in Peking Opera and define glottis closure states and mucosal wave changes during singing in the two roles. The range of singing in A4 (440 Hz) pitch in seven female Peking Opera singers was determined using two classic pieces of Peking Opera. Glottal changes during singing were examined by stroboscopic laryngoscope. The fundamental frequency of /i/ in the first 15 seconds of the two pieces and the /i/ pitch range were determined. The relative length of the glottis fissure and the relative maximum mucosal amplitude were calculated. Qingyi had significantly higher mean fundamental frequency than Laodan. The long-term average spectrum showed an obvious formant cluster near 3000 Hz in Laodan versus Qingyi. No formant cluster was observed in singing in the regular mode. Strobe laryngoscopy showed complete glottal closure in Laodan and incomplete glottal closure in Qingyi in the maximal glottis closure phase. The relative length of the glottis fissure of Laodan was significantly lower than that of Qingyi in the singing mode. The relative maximum mucosal amplitude of Qingyi was significantly lower than that of Laodan. The Laodan role and the Qingyi role in Peking Opera sing in a fundamental frequency range compatible with the respective use of da sang (big voice) and xiao sang (small voice). The morphological patterns of glottal changes also indicate that the Laodan role and the Qingyi role sing with da sang and xiao sang, respectively. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Comparison of two simulation systems to support robotic-assisted surgical training: a pilot study (Swine model).

PubMed

Whitehurst, Sabrina V; Lockrow, Ernest G; Lendvay, Thomas S; Propst, Anthony M; Dunlow, Susan G; Rosemeyer, Christopher J; Gobern, Joseph M; White, Lee W; Skinner, Anna; Buller, Jerome L

2015-01-01

To compare the efficacy of simulation-based training between the Mimic dV- Trainer and traditional dry lab da Vinci robot training. A prospective randomized study analyzing the performance of 20 robotics-naive participants. Participants were enrolled in an online da Vinci Intuitive Surgical didactic training module, followed by training in use of the da Vinci standard surgical robot. Spatial ability tests were performed as well. Participants were randomly assigned to 1 of 2 training conditions: performance of 3 Fundamentals of Laparoscopic Surgery dry lab tasks using the da Vinci or performance of 4 dV-Trainer tasks. Participants in both groups performed all tasks to empirically establish proficiency criterion. Participants then performed the transfer task, a cystotomy closure using the daVinci robot on a live animal (swine) model. The performance of robotic tasks was blindly assessed by a panel of experienced surgeons using objective tracking data and using the validated Global Evaluative Assessment of Robotic Surgery (GEARS), a structured assessment tool. No statistically significant difference in surgeon performance was found between the 2 training conditions, dV-Trainer and da Vinci robot. Analysis of a 95% confidence interval for the difference in means (-0.803 to 0.543) indicated that the 2 methods are unlikely to differ to an extent that would be clinically meaningful. Based on the results of this study, a curriculum on the dV- Trainer was shown to be comparable to traditional da Vinci robot training. Therefore, we have identified that training on a virtual reality system may be an alternative to live animal training for future robotic surgeons. Published by Elsevier Inc.

Health and innovation: economic dynamics and Welfare State in Brazil.

PubMed

Gadelha, Carlos Augusto Grabois; Braga, Patrícia Seixas da Costa

2016-11-03

The effective enforcement of the access to healthcare as fundamental right requires an important theoretical and political effort at linking the often contradictory economic and social dimensions of development. This study suggests the need for a systemic view of policies related to the industrial base and innovation in health and the construction of the Brazilian Unified National Health System (SUS). The authors investigate the relations between health, innovation, and development, seeking to show and update the political, economic, and social determinants of the recent Brazilian experience with the Health Economic-Industrial Complex (HEIC). They discuss how the agenda for innovation and domestic industrial production in health gained a central place in the project for construction of the SUS. The article thus seeks to link inherent issues from the agenda for development, production, and innovation to social policy in healthcare, as observed in recent years, and based on this analysis, points to political and conceptual challenges for implementing the SUS, especially as regards strengthening its technological and industrial base. As a byproduct, the article develops an analytical and factual focus on the consolidation of the HEIC in Brazil, both as a dynamic vector of industrial development, generating investment, income, employment, and innovations, and as a decisive element for reducing vulnerability and structural dependence in health. The authors aim to show that strengthening the SUS and orienting it to social needs is an essential part of building a social Welfare State in Brazil. Resumo: A efetivação da saúde como um direito fundamental exige importante esforço, teórico e político, de articulação das dimensões econômicas e sociais, por vezes contraditórias, do desenvolvimento. Este trabalho indica a necessidade de um olhar sistêmico das políticas relacionadas à base produtiva e de inovação em saúde e à construção do Sistema Único de Saúde (SUS). Investiga as relações entre saúde, inovação e desenvolvimento, buscando mostrar e atualizar os determinantes políticos, econômicos e sociais da experiência brasileira recente relacionada ao Complexo Econômico-Industrial da Saúde (CEIS). Mostra como a agenda da inovação e da produção nacional em saúde ganhou centralidade no projeto de construção do SUS. O artigo procura, assim, articular questões inerentes à agenda do desenvolvimento, da produção e da inovação com a política social em saúde, tal como observado nos últimos anos e, valendo-se de sua análise, aponta desafios políticos e conceituais para a efetivação do SUS, em especial no que se refere ao fortalecimento de sua base tecnológica e produtiva. Como desdobramento, desenvolve um enfoque analítico e factual que relaciona a consolidação do CEIS no Brasil tanto como um vetor dinâmico do desenvolvimento industrial, gerando investimento, renda, emprego e inovações, quanto como elemento decisivo para a redução da vulnerabilidade e da dependência estrutural em saúde. Procura mostrar que seu fortalecimento e direcionamento para as necessidades sociais é parte essencial da construção de um Estado de Bem-Estar Social no Brasi.

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

PubMed Central

Savitz, Jonathan; Hodgkinson, Colin A.; Martin-Soelch, Chantal; Shen, Pei-Hong; Szczepanik, Joanna; Nugent, Allison; Herscovitch, Peter; Grace, Anthony A.; Goldman, David; Drevets, Wayne C.

2013-01-01

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis. PMID:23365649

A High Fundamental Frequency (HFF)-based QCM Immunosensor for Tuberculosis Detection.

PubMed

Montoya, Angel; March, Carmen; Montagut, Yeison J; Moreno, Maria J; Manclus, Juan J; Arnau, Antonio; Jimenez, Yolanda; Jaramillo, Marisol; Marin, Paula A; Torres, Robinson A

2017-01-01

Tuberculosis, one of the oldest diseases affecting human beings, is still considered as a world public health problem by the World Health Organization. Therefore, there is a need for new and more powerful analytical methods for early illness diagnosis. With this idea in mind, the development of a High Fundamental Frequency (HFF) piezoelectric immunosensor for the sensitive detection of tuberculosis was undertaken. A 38 kDa protein secreted by Mycobacterium tuberculosis was first selected as the target biomarker. Then, specific monoclonal antibodies (MAbs) were obtained. Myc-31 MAb, which showed the highest affinity to the analyte, was employed to set up a reference enzyme-linked immunosorbent assay (ELISA) with a limit of detection of 14 ng mL-1 of 38 kDa antigen. For the development of the HFF piezoelectric immunosensor, 100 MHz quartz crystals were used as transducer elements. The gold electrode surface was functionalized by covalent immobilization of the target biomarker through mixed self-assembled monolayers (mSAM) of carboxylic alkane thiols. A competitive immunoassay based on Myc-31 MAb was integrated with the transducer as sensing bio-recognition event. Reliable assay signals were obtained using low concentrations of antigen for functionalization and MAb for the competitive immunoassay. Under optimized conditions, the HFF immunosensor calibration curve for 38 kDa determination showed a limit of detection as low as 11 ng mL-1 of the biomarker. The high detectability attained by this immunosensor, in the picomolar range, makes it a promising tool for the easy, direct and sensitive detection of the tuberculosis biomarker in biological fluids such as sputum. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessing the dependency of the fine structure constant on gravity using hot DA white dwarfs

NASA Astrophysics Data System (ADS)

Barstow, Martin

2016-10-01

Variation of fundamental constants is a common theme of many theories of quantum gravity and Grand Unification. Using spectra obtained with the Hubble Space Telescope, it has been shown by Berengut et al. (2013), and Bagdonaite et al. (2014), that it is possible to place strong constraints on gravitational variations of the fine structure constant (alpha), and the proton to electron mass ratio (mu) in white dwarf stars.As part of the UV initiative, we propose to observe four hot DA white dwarf stars using STIS with the E140H grating, totalling 12 orbits. These four stars have been chosen so as to have a wide range of masses, allowing a full exploration of the compactness parameter space (M/R). We will measure several absorption features of Fe V and Ni V, and extract any potential variation in alpha in a manner similar to Berengut et al. (2013).This proposal will be a significant advance in the effort to detect gravitational variations in alpha. A confirmed detection of alpha variation would have extensive consequences for fundamental physics, cosmology, and would also signal the breakdown of Einstein's Equivalence principle, and hence, general relativity. Furthermore, a null detection would also allow strong limits to be placed on any potential alpha variation in a strong gravitational field.

Local probe studies on lattice distortions and electronic correlations in manganites

NASA Astrophysics Data System (ADS)

Lopes, Armandina Maria Lima

Nesta tese apresenta-se um estudo experimental das distorcoes locais e correlacoes electronicas em oxidos magneticos com magnetoresistencia colossal. A tecnica de sonda local - Correlacao Angular Perturbada - e utilizada em amostras caracterizadas quanto as suas propriedades macroscopicas nomeadamente propriedades estruturais, magneticas e electricas, tendo em vista a obtencao de informacao microscopica relevante via gradiente de campo electrico e campo magnetico hiperfino, focando em particular os seguintes aspectos: -Distorcoes de rede e agregados de polaroes no sistema LaMnO3+Delta. E apresentado um estudo dos gradientes de campo electrica e campo magnetico hiperfino em amostras representativas do sistema LaMnO3+Delta, correlacionando estas propriedades locais com a caracterizacao das propriedades macroscopicas, efectuada nas mesmas amostras. Desta forma, foi possivel estudar a natureza microscopica das distorcoes polaronicas. Foi dada especial atencao ao composto com composicao LaMnO3.12 uma vez que este e um sistema padrao de uma manganite ferromagnetica-isoladora que apresenta uma transicao estrutural romboedrica (R)-ortorrombica (O) perto da temperatura ambiente. O estudo revelou que agregados de distorcoes locais sobrevivem ate 776 K, na fase de estrutura media mais simetrica (romboedrica), onde, por simetria, os octaedros MnO6 deveriam ser regulares. Estas distorcoes sao semelhantes as observadas no sistema LaMnO3 onde os octaedros MnO6 apresentam uma distorcao Jahn-Teller colectiva. Com a diminuicao da temperatura observa-se um aumento continuo destes agregados. Abaixo de uma temperatura critica estas distorcoes relaxam acomodando-se numa estrutura com reduzidas distorcoes Jahn-teller. Verificou-se tambem que a transicao estrutural (macroscopica) pode ser entendida como uma transicao de percolacao dos ambientes microscopicos. -Coexistencia das ordens electrica e magnetica no sistema Pr1-xCaxMnO3. E apresentado o primeiro estudo de gradiente de campo electrico no sistema Pr1-xCaxMnO3. Este estudo foi efectuado numa larga gama de temperaturas permitindo estudar localmente as diversas transicoes que este sistema apresenta. Em particular, na regiao do diagrama de fases onde existe ordenamento de carga e orbital (0.32

Uma grade de perfis teóricos para estrelas massivas em transição

NASA Astrophysics Data System (ADS)

Nascimento, C. M. P.; Machado, M. A.

2003-08-01

Na XXVIII Reunião Anual da Sociedade Astronômica Brasileira (2002) apresentamos uma grade de perfis calculados de acordo com os pontos da trajetória evolutiva de metalicidade solar, Z = 0.02 e taxa de perda de massa () padrão, para estrelas com massa inicial de 25, 40, 60, 85 e 120 massas solares. Estes perfis foram calculados com o auxílio de um código numérico adequado para descrever os ventos de objetos massivos, supondo simetria esférica, estacionaridade e homogeneidade. No presente trabalho, apresentamos a complementação da grade com os perfis teóricos relativos às trajetórias de Z = 0.02 com taxa de perda de massa dobrada em relação a padrão (2´), e de metalicidade Z = 0.008. Para cada ponto das três trajetórias obtemos os perfis teóricos de Ha, Hb, Hg e Hd, e como esperado eles se apresentam em pura emissão, pura absorção ou em P-Cygni. Para valores de taxa de perda de massa muito baixos (~10-7) não há formação de linhas, o que é visto nos primeiros pontos em todas as trajetórias. Em geral, para um mesmo ponto a componente de emissão diminui e a absorção aumenta de Ha para Hd. É verificado que as trajetórias com Z = 0.02 e padrão possuem menos circuitos (loops) do que as com metalicidade Z = 0.02 e 2´ padrão, e seus perfis são, em geral, menos intensos. Em relação a trajetória de Z = 0.008, verifica-se menos circuitos e maior variação em luminosidade, e seus perfis mostram-se em, algumas trajetórias, mais intensos. Verificamos também que, pontos distintos em uma mesma trajetória, apresentam perfis diferentes para valores similares de luminosidade e temperatura efetiva. Sendo assim, uma grade de perfis teóricos parece ser útil para fornecer uma informação preliminar sobre o estágio evolutivo de uma estrela massiva.

["Anything goes"?: the implicit dialogue between Paul Feyerabend and two Brazilian researchers, Maurício da Rocha e Silva and Newton Freire-Maia].

PubMed

Bastos, Francisco Inácio

2010-03-01

The philosopher Paul Feyerabend and Brazilian scientists Maurício da Rocha e Silva and Newton Freire-Maia were contemporaries and lived surrounded by the fundamental dilemnas of science. The anarchist proposal of Feyerabend, then embryonic, was formulated in parallel by Rocha e Silva in his criticism of the scientific method. Two decades later, Feyerabend's ideas seemed implicitly to stimulate Newton Freire-Maia in his reflections on science. The web of interrelationships in the ideas of these three men - who never interacted - touches on central issues for Brazilian science from 1960 to 1980, a period in which the latter is consolidated in a dialogue with the nascent reflection on science and the scientific method in Brazil.

Maximal privacy without coherence.

PubMed

Leung, Debbie; Li, Ke; Smith, Graeme; Smolin, John A

2014-07-18

Privacy is a fundamental feature of quantum mechanics. A coherently transmitted quantum state is inherently private. Remarkably, coherent quantum communication is not a prerequisite for privacy: there are quantum channels that are too noisy to transmit any quantum information reliably that can nevertheless send private classical information. Here, we ask how much private classical information a channel can transmit if it has little quantum capacity. We present a class of channels N(d) with input dimension d(2), quantum capacity Q(N(d)) ≤ 1, and private capacity P(N(d)) = log d. These channels asymptotically saturate an interesting inequality P(N) ≤ (1/2)[log d(A) + Q(N)] for any channel N with input dimension d(A) and capture the essence of privacy stripped of the confounding influence of coherence.

Innovation, development, and financing of institutions of Higher Education in health.

PubMed

Poz, Mario Roberto Dal; Couto, Maria Helena Costa; Franco, Thais de Andrade Vidaurre

2016-11-03

The article analyzes the configuration and trends in institutions of Higher Education and their relationship as components of the Health Economic-Industrial Complex (HEIC). The expansion of higher education is part of the transition from elite to mass systems, with tensions between quantitative and qualitative aspects. Such changes reflect different cultures and are related to international phenomena such as globalization, economic transformations, the development of new information and communication technologies, and the emergence of an international knowledge network. The scale and content of these changes vary according to the expansion and institutional reconfiguration of educational systems, as well as the link between state and society. Market expansion for private higher education stirs competition, shapes business clusters, modifies training processes, and raises new public policy challenges. Resumo: Este artigo analisa a configuração e as tendências das instituições de Ensino Superior de saúde no seu relacionamento enquanto componentes do Complexo Econômico Industrial da Saúde (CEIS). A expansão do Ensino Superior é parte da transição de sistemas de elite para sistemas de massa, com tensionamentos entre aspectos quantitativos e qualitativos. Essas mudanças refletem diferentes culturas e se relacionam com fenômenos de escopo mundial como globalização, transformações econômicas, desenvolvimento de novas tecnologias de comunicação e informação, e emergência de uma rede internacional de conhecimento. A escala e o conteúdo dessas mudanças variam com a ampliação dos sistemas de ensino e na reconfiguração institucional, bem como na articulação entre Estado e sociedade. A ampliação do mercado privado no ensino acirra a competitividade, conformando conglomerados empresariais, alterando processos de formação e forjando novos desafios para as políticas públicas.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Role of Nurr1 in the Generation and Differentiation of Dopaminergic Neurons from Stem Cells.

PubMed

Rodríguez-Traver, Eva; Solís, Oscar; Díaz-Guerra, Eva; Ortiz, Óscar; Vergaño-Vera, Eva; Méndez-Gómez, Héctor R; García-Sanz, Patricia; Moratalla, Rosario; Vicario-Abejón, Carlos

2016-07-01

NURR1 is an essential transcription factor for the differentiation, maturation, and maintenance of midbrain dopaminergic neurons (DA neurons) as it has been demonstrated using knock-out mice. DA neurons of the substantia nigra pars compacta degenerate in Parkinson's disease (PD) and mutations in the Nurr1 gene have been associated with this human disease. Thus, the study of NURR1 actions in vivo is fundamental to understand the mechanisms of neuron generation and degeneration in the dopaminergic system. Here, we present and discuss findings indicating that NURR1 is a valuable molecular tool for the in vitro generation of DA neurons which could be used for modeling and studying PD in cell culture and in transplantation approaches. Transduction of Nurr1 alone or in combination with other transcription factors such as Foxa2, Ngn2, Ascl1, and Pitx3, induces the generation of DA neurons, which upon transplantation have the capacity to survive and restore motor behavior in animal models of PD. We show that the survival of transplanted neurons is increased when the Nurr1-transduced olfactory bulb stem cells are treated with GDNF. The use of these and other factors with the induced pluripotent stem cell (iPSC)-based technology or the direct reprogramming of astrocytes or fibroblasts into human DA neurons has produced encouraging results for the study of the cellular and molecular mechanisms of neurodegeneration in PD and for the search of new treatments for this disease.

A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee Brain

PubMed Central

Tedjakumala, Stevanus R.; Rouquette, Jacques; Boizeau, Marie-Laure; Mesce, Karen A.; Hotier, Lucie; Massou, Isabelle; Giurfa, Martin

2017-01-01

Dopamine (DA) plays a fundamental role in insect behavior as it acts both as a general modulator of behavior and as a value system in associative learning where it mediates the reinforcing properties of unconditioned stimuli (US). Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. We used tyrosine hydroxylase (TH) immunoreactivity (ir) to ensure that the neurons detected synthesize DA endogenously. We found three main dopaminergic clusters, C1–C3, which had been previously described; the C1 cluster is located in a small region adjacent to the esophagus (ES) and the antennal lobe (AL); the C2 cluster is situated above the C1 cluster, between the AL and the vertical lobe (VL) of the mushroom body (MB); the C3 cluster is located below the calyces (CA) of the MB. In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. Additional smaller processes and clusters were found and are described. The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning. PMID:28740466

Next Generation Workload Management System For Big Data on Heterogeneous Distributed Computing

DOE PAGES

Klimentov, A.; Buncic, P.; De, K.; ...

2015-05-22

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS and ALICE are the largest collaborations ever assembled in the sciences and are at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, both experiments rely on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Managementmore » System (WMS) for managing the workflow for all data processing on hundreds of data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. The scale is demonstrated by the following numbers: PanDA manages O(10 2) sites, O(10 5) cores, O(10 8) jobs per year, O(10 3) users, and ATLAS data volume is O(10 17) bytes. In 2013 we started an ambitious program to expand PanDA to all available computing resources, including opportunistic use of commercial and academic clouds and Leadership Computing Facilities (LCF). The project titled 'Next Generation Workload Management and Analysis System for Big Data' (BigPanDA) is funded by DOE ASCR and HEP. Extending PanDA to clouds and LCF presents new challenges in managing heterogeneity and supporting workflow. The BigPanDA project is underway to setup and tailor PanDA at the Oak Ridge Leadership Computing Facility (OLCF) and at the National Research Center "Kurchatov Institute" together with ALICE distributed computing and ORNL computing professionals. Our approach to integration of HPC platforms at the OLCF and elsewhere is to reuse, as much as possible, existing components of the PanDA system. Finally, we will present our current accomplishments with running the PanDA WMS at OLCF and other supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications.« less

Next Generation Workload Management System For Big Data on Heterogeneous Distributed Computing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klimentov, A.; Buncic, P.; De, K.

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS and ALICE are the largest collaborations ever assembled in the sciences and are at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, both experiments rely on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Managementmore » System (WMS) for managing the workflow for all data processing on hundreds of data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. The scale is demonstrated by the following numbers: PanDA manages O(10 2) sites, O(10 5) cores, O(10 8) jobs per year, O(10 3) users, and ATLAS data volume is O(10 17) bytes. In 2013 we started an ambitious program to expand PanDA to all available computing resources, including opportunistic use of commercial and academic clouds and Leadership Computing Facilities (LCF). The project titled 'Next Generation Workload Management and Analysis System for Big Data' (BigPanDA) is funded by DOE ASCR and HEP. Extending PanDA to clouds and LCF presents new challenges in managing heterogeneity and supporting workflow. The BigPanDA project is underway to setup and tailor PanDA at the Oak Ridge Leadership Computing Facility (OLCF) and at the National Research Center "Kurchatov Institute" together with ALICE distributed computing and ORNL computing professionals. Our approach to integration of HPC platforms at the OLCF and elsewhere is to reuse, as much as possible, existing components of the PanDA system. Finally, we will present our current accomplishments with running the PanDA WMS at OLCF and other supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications.« less

Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

PubMed Central

Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

2016-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

Nucleus accumbens invulnerability to methamphetamine neurotoxicity.

PubMed

Kuhn, Donald M; Angoa-Pérez, Mariana; Thomas, David M

2011-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure.

Innovation and communicative action: health management networks and technologies.

PubMed

Rivera, Francisco Javier Uribe; Artmann, Elizabeth

2016-11-03

This article discusses elements of a theory of innovation from the perspective of innovation networks and social construction of technology, based on Habermas' Theory of Communicative Action and authors from the Sociology of Innovation. Based on the theoretical framework of the communicative production of scientific facts, we focus on innovation management as a basic dimension that must meet some organizational and methodological requirements in order to power its results. We present and discuss instruments such as Situational Planning, Prospective Analysis, Strategic Portfolio Management, and Networks Management that can help deal with the challenge of innovation and exploration of the future. We conclude that network organizational formats centered on reflexivity of interdisciplinary groups and planning approaches that encourage innovation criteria in assessing the attractiveness of activities and that help anticipate forms of innovation through systematic prospective analysis can potentiate the process of generating innovation as a product of networks. Resumo: No artigo são discutidos elementos de uma teoria da inovação numa perspectiva de redes de inovação e de construção social da tecnologia, a partir da Teoria do Agir Comunicativo de Habermas e de autores da Sociologia da Inovação. Com base no marco teórico da produção comunicativa de fatos científicos, focamos a gestão da inovação como uma dimensão fundamental que deve contemplar alguns requisitos, tanto de natureza organizacional quanto metodológica, para potencializar seus resultados. Apresentamos e discutimos instrumentos como o Planejamento Situacional, a Análise Prospectiva, a Gestão Estratégica de Portfólios e a Gestão de Redes que podem contribuir para o desafio da inovação e exploração do futuro. Conclui-se que formas organizativas em rede, centradas na reflexividade de grupos interdisciplinares, e enfoques de planejamento que estimulem o uso de critérios de inovação na avaliação da atratividade das atividades e que ajudem a antecipar formas de inovação por meio de uma análise prospectiva sistemática podem potencializar o processo de geração da inovação como produto de redes.

Distributed Low Temperature Combustion: Fundamental Understanding of Combustion Regime Transitions

DTIC Science & Technology

2016-09-07

behaviour as compared to ethanol. The latter fuel has also been considered along with methane. Work has also been performed on the further assessment of... behaviour as compared to ethanol. The latter fuel has also been considered along with methane. Work has also been performed on the further assess- ment of...identification of various combustion gas states. A range of Damköhler numbers (Da) from the conventional propagating flamelet regime well into the distributed

Abordaje a la Cisterna Ambiens

PubMed Central

Ajler, Pablo; Bravo, Michael Cruz; Garategui, Lucas; Goldschmidt, Ezequiel; Isolan, Gustavo; Campero, Álvaro

2016-01-01

Resumen Objetivo: Describir paso a paso el abordaje a la cisterna ambiens por la vía suboccipital retrosigmoidea supracerebelosa infratentorial (SRSI). Descripción: El abordaje SRSI se realiza de la misma manera que el abordaje suboccipital retrosigmoideo (SR), utilizado habitualmente para acceder a la patología del ángulo pontocerebeloso, con las siguientes modificaciones: (1) utilizamos siempre la posición semisentado, (2) la craneotomia-craniectomia debe exponer el seno transverso y extenderse 5 cm medialmente hacia el inion, (3) al realizar la apertura dural es necesario rebatir la duramadre junto con el seno transverso hacia cefálico con puntos de tracción, (4) bajo magnificación con microscopio quirúrgico se debe realizar la apertura de la cisterna cerebelobulbar para drenar líquido cefalorraquídeo, (5) en el plano supracerebeloso es fundamental cortar las bridas aracnoidales y de ser necesario debemos coagular y cortar las venas puente, todas estas maniobras sumadas al efecto de la gravedad brindan mayor apertura del corredor supracerebeloso. Conclusión: El abordaje a la cisterna ambiens por la vía SRSI es una opción segura para el acceso de patologías tumorales que se alojan en esta zona con un componente predominantemente infratentorial. PMID:27999709

Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.

PubMed

Muñoz, David; Serrano, Maria K; Hernandez, Maria E; Haller, Ross; Swanson, Tamara; Slaton, Joel W; Sinha, Akhouri A; Wilson, Michael J

2017-12-01

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60kDa, but did not affect activities of MMP-2, MMP-9, or the 75kDa caseinolytic activity. The 22, 42, and 60kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer. Copyright © 2017. Published by Elsevier Inc.

Um Breve Balanço dos Estudos em Astronomia e Educação no Brasil no Período de 2010 a 2013

NASA Astrophysics Data System (ADS)

Goncalves, Erica de Oliveira; Kern, C.

2014-10-01

No Brasil, as pesquisas em ensino de astronomia para a Educação Básica vem ganhando destaque. Posto como importante área do conhecimento para estudantes e professores, os estudos em astronomia conquistam espaços nos documentos oficiais da educação e nos currículos escolares. Diante desse cenário, fez-se, neste trabalho, um mapeamento no banco de dados da Biblioteca Digital Brasileira de Teses e Dissertações , com base nas palavras-chave "astronomia" e "educação" no período de 2010 a 2013. Para compor o que aqui denominamos de balanço da área de estudo, foram selecionados trabalhos e analisados os títulos, os resumos, as considerações finais e as referências, bem como identificamos as fontes epistemológicas correntes nas pesquisas de pós-graduação no período supracitado. Identificou-se, na maior parte dos trabalhos pesquisados, referenciais teóricos relacionados & agrave; área de física, ciências e astronomia que envolvem discussões sobre currículo e práticas pedagógicas vinculados ao ensino de astronomia no ensino fundamental e médio da Educação Bãsica e nos cursos de formação de professores.

Estudio de la formación de galaxias espirales en un modelo de agregación jerárquica

NASA Astrophysics Data System (ADS)

Tissera, P.; Saiz, A.; Dominguez-Tenreiro, R.

El estudio de formación de galaxias espirales ha llevado al desarrollo de numerosos modelos teóricos (e.g. White & Rees 1978). En la actualidad, el modelo más aceptado predice la formación de una galaxia espiral a partir del colapso disipativo del gas en el pozo de potencial de un halo oscuro, conservando su momento angular específco (Fall & Efstathiou 1980). En los últimos años, ha sido posible realizar simulaciones numéricas hidrodinámicas, las cuales describen la evolución conjunta de la materia oscura y los bariones. Estos experimentos han señalado la dificultad de formar estructuras discoidales con propiedades consistentes con las observaciones, en modelos de agregación jerárquica. El problema principal se origina en la pérdida catastrófica de momento angular de la componente disipativa, durante el proceso de ensamblaje de los objetos, a través de la fusión de subestructura (Navarro & Steinmetz 1997). Estos experimentos no incluían procesos de formación estelar. En este trabajo, se expondrán resultados de simulaciones hidrodinámicas cosmológicas, incluyendo formación estelar (Tissera et al 1997), donde ha sido posible reproducir objetos discoidales con contrapartida observacional. El elemento fundamental ha sido la formación de bulbos estelares, los cuales han evitado la pérdida catastrófica de momento angular de los bariones. Se encontró que los discos exponenciales puramente gaseosos son altamente inestables y suceptibles de generar barras, responsables de la pérdida de momento angular y la caída violenta del gas hacia la región central. Estas inestabilidades son fácilmente inducidas durante interacciones y fusiones con objetos vecinos (Barnes & Hernquist 1996). Un bulbo estelar (o un objeto masivo y compacto) estabiliza el disco ante perturbaciones externas, asegurándole un potencial simétrico (Sellwood & Moore 1998, Van der Bosch 1998). En este caso, el gas en el disco no pierde completamente su momento angular intrínseco durante las fusiones, sino que, las sobrevive aportando una contribución distinta de cero, a partir de la cual el disco se regenera acretando en una segunda etapa, gas del halo de acuerdo al modelo tradicional de Fall & Efstathiou.

Integration Of PanDA Workload Management System With Supercomputers for ATLAS and Data Intensive Science

NASA Astrophysics Data System (ADS)

Klimentov, A.; De, K.; Jha, S.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Wells, J.; Wenaus, T.

2016-10-01

The.LHC, operating at CERN, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than grid can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility. Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This implementation was tested with a variety of Monte-Carlo workloads on several supercomputing platforms for ALICE and ATLAS experiments and it is in full pro duction for the ATLAS since September 2015. We will present our current accomplishments with running PanDA at supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications, such as bioinformatics and astro-particle physics.

Prevendo a atividade solar através de redes neurais nebulosas

NASA Astrophysics Data System (ADS)

Martin, V. A. F.; Poppe, P. C. R.

2003-08-01

Atualmente, a integração de redes neurais com técnicas da Matemática Nebulosa (Fuzzy Sets), tem sido usada robustamente para fazer previsões em vários sistemas físicos. Este trabalho representa uma continuidade da contribuição apresentada anteriormente durante a XXVIIa Reunião Anual da SAB, onde exploramos a aplicação de redes neurais para previsões futuras de séries temporais. Para este, enfatizamos o uso da técnica ANFIS (Adaptative Neuro-Fuzzy Inference System), que consiste em uma rede do tipo back-propagation, onde os dados são processados em uma camada intermediária, tendo numa camada de saída, os dados numéricos. Para que a previsão seja feita com sucesso utilizando-se técnicas matemáticas adequadas, é fundamental a existência de uma série razoavelmente longa de modo que a dinâmica contida nesta possa ser melhor extraída pela rede neural. Nesse sentido, foram utilizados novamente os dados históricos das manchas do Sol (1818-2002) afim de verificar o comportamento futuro da atividade solar (Ciclos de Schawbe) a partir da técnica descrita acima. Previsões realizadas para o ciclo anterior (n.22, máximo de 158,5 em julho de 1989), bem como para o atual (n.23, máximo de 153 em setembro de 2000), apontam valores bastante coerentes com os publicados na literatura, levando em consideração, respectivamente, as barras de erros associadas: 166+/-18 e 160+/-14. Para o próximo ciclo de Schawbe (2006-2017), nossa previsão aponta o valor de 172+/-23 como máximo para o primeiro semestre de 2011 (Abril +/- 3 meses). A ANFIS acompanha de maneira satisfatória o movimento das séries estudadas durante o treinamento e durante a verificação (menor dispersão das funções de pertinência), com erro absoluto inferior a 20 por cento.

A bone tissue engineering strategy based on starch scaffolds and bone marrow cells cultured in a flow perfusion bioreactor

NASA Astrophysics Data System (ADS)

Gomes, Maria Manuela Estima

A Engenharia de Tecidos e uma area cientifica em continua expansao. Os desenvolvimentos conseguidos por esta area tem contribuido significativamente para diversos avancos no campo da Medicina Regenerativa. Esta ciencia interdisciplinar combina os conhecimentos de diversas outras areas, tao distintas como a Engenharia de Materiais e a Biologia, com o objectivo de desenvolver substitutos sinteticos para tecidos humanos. Para se atingir este objectivo utilizam-se, de uma forma generica, combinacoes especificas de celulas e de um material de suporte tridimensional com propriedades adequadas, gerando um material hibrido cujas caracteristicas podem ainda ser moduladas atraves do sistema de cultura usado. A presente tese e centrada no desenvolvimento de estrategias de engenharia de tecido osseo baseadas na cultura in vitro de celulas previamente "semeadas" num suporte tridimensional ("scaffold"). Esta estrategia permite que as celulas adiram ao suporte, proliferem e segreguem matriz extracelular especifica do tecido osseo, ate se obter um substituto artificial funcional com caracteristicas do tecido original, que pode finalmente ser transplantado para tratar o defeito em causa. Para que uma estrategia deste tipo seja bem sucedida, pelo menos tres componentes fundamentais devem ser cuidadosamente estudados: o material de suporte (scaffold), as celulas a usar e o sistema de cultura in vitro. Dai que os principais objectivos desta tese estejam relacionados com estes tres aspectos, nomeadamente: • Desenvolvimento de scaffolds biodegradaveis a partir de polimeros a base de amido de milho que induzam a adesao e proliferacao celular e que apresentem propriedades adequadas, tais como a porosidade e interconectividade entre poros, de forma a proporcionar um ambiente que favoreca o desenvolvimento in vitro de um material hibrido com caracteristicas similares ao osso humano. • Estudo da utilizacao de celulas da medula ossea como uma potencial fonte de celulas para engenharia do tecido osseo, uma vez que estas celulas podem ser facilmente recolhidas do proprio paciente a tratar por metodos nao-invasivos (bioppsia) e em quantidades suficientes. Alem disso, tratando-se de uma fonte de celulas autologas (obtidas do proprio paciente) permitem evitar os riscos de transmissao de doencas contagiosas e/ou de rejeicao pelo sistema imunologico. • Estudo da influencia das condicoes de cultura in vitro geradas por um bioreactor de perfusao (em comparacao com os metodos tradicionais de cultura em condicoes estaticas) no desenvolvimento dos materiais hibridos, compostos pelas celulas e scaffolds, assim como as interaccoes do ambiente proporcionado por este sistema de cultura com as diferentes estruturas/arquitecturas e porosidades dos scaffolds utilizados. Estes objectivos convergem para o objectivo geral desta tese que consistiu no desenvolvimento de uma terapia de engenharia do tecido osseo alternativa as existentes e com potencial para vir a ser posteriormente utilizada na pratica clinica. Este objectivo foi avaliado atraves do estudo da funcionalidade dos materiais hibridos obtidos em diferentes condicoes de cultura in vitro (e utilizando diferentes scaffolds), partindo do principio que o sistema de perfusao poderia eventualmente superar as limitacoes de difusao tipicas dos sistema de cultura estatica e simultaneamente proporcionar estimulos mecânicos as celulas, semelhantes aos encontrados em condicoes fisiologicas. (Abstract shortened by ProQuest.).

Effect of the exercise of walkers performed in public squares with spontaneous or prescribed intensity on post-exercise hypotension.

PubMed

Silva, Taís Feitosa da; Souza, Alesandra Araújo de; Lima, Fabiano Ferreira de; Suassuna, Jennifer Ariely Sales; Couto, Henrique Eduardo Paiva Lira do; Tenório, Gustavo Roque; Silva, Maria Irene de Andrade Gomes; Dias, Guilherme Leandebal Bonifácio; Silva, Alexandre Sérgio

2017-07-20

To quantify the intensity adopted by walkers in public squares and check the occurrence and magnitude of post-exercise hypotension in the spontaneously adopted intensity and in a prescribed intensity. In 98 volunteers (38 of them being hypertensive), walkers in public squares of the city of João Pessoa, State of Paraíba, Brazil, we have identified the intensity of a usual training monitored by heart rate and we have investigated the occurrence and magnitude of post-exercise hypotension. Subsequently, participants were instructed to walk with moderate intensity. Blood pressure was measured after rest and during post-exercise recovery. Of the total participants, 41% of the hypertensive and 36% of the normotensive individuals walked with light intensity. With the prescription, intensity increased to 55% and 52%, for the hypertensive and normotensive individuals, respectively. In the usual and prescribed intensity, the hypertensive individuals had post-exercise hypotension of -3.7±11.6 mmHg and -4.72±12.8 mmHg, respectively. There was no correlation between post-exercise hypotension and the initial systolic component of the hypertensive individuals (r2 = 0.2; p < 0.002). Walkers in public squares choose light intensity for walking. When they exercise with the prescribed intensity, they increase the intensity, but the magnitude of the PEH is not increase with this guidance. Quantificar a intensidade adotada por caminhantes em praças públicas e verificar a ocorrência e a magnitude da hipotensão pós-exercício na intensidade espontaneamente adotada e em uma intensidade prescrita. Em 98 voluntários (38 hipertensos), caminhantes em praças públicas da cidade de João Pessoa, PB, identificamos a intensidade de um treino habitual monitorada por meio da frequência cardíaca e averiguamos a ocorrência e magnitude de hipotensão pós-exercício. Posteriormente, os participantes foram instruídos a caminhar com intensidade moderada. A pressão arterial foi aferida após o repouso e durante a recuperação pós-exercício. Do total de participantes, 41% dos hipertensos e 36% dos normotensos caminhavam com intensidade leve. Com a prescrição, a intensidade aumentou para 55% e 52%, para hipertensos e normotensos. Na intensidade habitual e prescrita, os hipertensos obtiveram hipotensão pós-exercício de -3,7±11,6 mmHg e -4,72±12,8 mmHg. Houve correlação entre hipotensão pós-exercício e o componente sistólico inicial dos hipertensos (r2 = 0,2; p < 0,002). Caminhantes em praças públicas selecionam intensidade leve para realização de caminhada. Quando realizam exercício com intensidade prescrita, aumentam discretamente a intensidade, mas não obtêm aumento da magnitude da HPE com esta orientação.

[Nursing in palliative care to children and adolescents with cancer: integrative literature review].

PubMed

da Costa, Thailly Faria; Ceolim, Maria Filomena

2010-12-01

Pediatric palliative care is a challenge for nursing because it requires emotional balance and knowledge about its specific features. This study is an integrative literature review that aims to identify nursing actions in palliative care for children and adolescents with cancer, considering peculiarities of the disease and dying process. The review was performed by searching for articles indexed in Biblioteca Virtual da Adolescência (Adolec), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and PubMed databases from January 2004 till May 2009. From 29 references found, six met inclusion criteria. Results show teamwork, home care, pain management, dialogue, family support and particularities of childhood cancer fundamental tools for nursing in palliative care. The complexity of care in this situation requires solidarity, compassion, support and relieving suffering.

Spatiotemporal Distribution and Population Structure of Monokalliapseudes schubarti (Tanaidacea: Kalliapseudidae) in an Estuary in Southern Brazil

PubMed Central

Freitas-Júnior, Felipe; Christoffersen, Martin Lindsey; de Araújo, Joafrâncio Pereira; Branco, Joaquim Olinto

2013-01-01

Monokalliapseudes schubarti is an endemic tanaidacean microcrustacean from southeastern Brazil to Uruguay inhabiting low energy estuaries. Saco da Fazenda is located in the estuary of the Itajaí-Açú River, state of Santa Catarina, Brazil. It is exposed to strong anthropic impact and receives intensive flows of domestic wastewater, solid residues, and drainage activities. Specimens of M. schubarti were collected monthly, in the intertidal and subtidal regions of Saco da Fazenda, in four stations defined as a function of the physiography of the environment during the period of July 2003 to June 2004. Fecundity values were high, with continuous reproductive activity during the whole period of study. The greatest population densities were observed in the intertidal region, where they are nevertheless intensely consumed by birds, swimming crabs, and fish. This species represents a fundamental link in the food chain of Saco da Fazenda, transferring energy from the detritus level to higher trophic levels. Habitat disturbance and high organic matter may represent factors controlling the distribution of populations of M. schubarti. For this reason, the species may be used to monitor anthropic effects in estuarine areas. PMID:24298211

Music and the nucleus accumbens.

PubMed

Mavridis, Ioannis N

2015-03-01

Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

Construção de um catálogo de aglomerados abertos para estudo da dinâmica da estrutura espiral da Galáxia

NASA Astrophysics Data System (ADS)

Carlos, I. M.; Lépine, J. R. D.

2003-08-01

Os aglomerados abertos são objetos de grande valor para o estudo da dinâmica da Galáxia devido esses objetos terem uma faixa de idade relativamente ampla. O trabalho visa estudar a dinâmica da estrutura espiral da Galáxia principalmente através do uso desses aglomerados, uma vez que o estudo da cinemática desses objetos é fundamental para esse objetivo. Nosso grupo trabalha no sentido de construir uma base de dados de aglomerados abertos contendo coordenadas, distância, idade, movimentos próprios e velocidades radiais e já disponibiliza uma nova versão do catálogo de aglomerados abertos o qual é uma compilação de edições anteriores, principalmente Lynga (1987), Mermilliod (1995) e ESO-B (Lauberts 1982). Nossa amostra possui cerca de 1630 aglomerados, mas nem todos os parâmetros acima citados foram determinados em sua totalidade. Para determinarmos esses parâmetros, derivamos as cores intrínsecas das estrelas membro de cada aglomerado a partir de seus tipos espectrais (busca feita no SIMBAD) obtendo assim o excesso de cor individual. A distribuição dos excessos de cor foi então utilizada para derivarmos o avermelhamento médio para cada aglomerado. De maneira similar, os tipos espectrais foram usados para estimar as magnitudes absolutas, e com as magnitudes absolutas e aparentes determinamos a respectiva distribuição do módulo de distância e finalmente a distância. Para determinar as idades foram confeccionados os diagramas cor-magnitude das estrelas de cada aglomerado onde foram superpostas a Seqüência Principal de Idade Zero (ZAMS). Superpomos a ZAMS de Schmidt-Kaler e isócronas de composição solar. Essas isócronas foram usadas para determinação das idades dos aglomerados. Uma vez que não temos ainda resultados finais, apresentamos então alguns diagramas cor-magnitude os quais foram usados para determinação, principalmente, da distância e idade dos aglomerados.

Distributed data analysis in ATLAS

NASA Astrophysics Data System (ADS)

Nilsson, Paul; Atlas Collaboration

2012-12-01

Data analysis using grid resources is one of the fundamental challenges to be addressed before the start of LHC data taking. The ATLAS detector will produce petabytes of data per year, and roughly one thousand users will need to run physics analyses on this data. Appropriate user interfaces and helper applications have been made available to ensure that the grid resources can be used without requiring expertise in grid technology. These tools enlarge the number of grid users from a few production administrators to potentially all participating physicists. ATLAS makes use of three grid infrastructures for the distributed analysis: the EGEE sites, the Open Science Grid, and Nordu Grid. These grids are managed by the gLite workload management system, the PanDA workload management system, and ARC middleware; many sites can be accessed via both the gLite WMS and PanDA. Users can choose between two front-end tools to access the distributed resources. Ganga is a tool co-developed with LHCb to provide a common interface to the multitude of execution backends (local, batch, and grid). The PanDA workload management system provides a set of utilities called PanDA Client; with these tools users can easily submit Athena analysis jobs to the PanDA-managed resources. Distributed data is managed by Don Quixote 2, a system developed by ATLAS; DQ2 is used to replicate datasets according to the data distribution policies and maintains a central catalog of file locations. The operation of the grid resources is continually monitored by the Ganga Robot functional testing system, and infrequent site stress tests are performed using the Hammer Cloud system. In addition, the DAST shift team is a group of power users who take shifts to provide distributed analysis user support; this team has effectively relieved the burden of support from the developers.

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs.

PubMed

Smolich, Joseph J

2014-02-15

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% (P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

The Label Matters: μPET Imaging of the Biodistribution of Low Molar Mass 89Zr and 18F-Labeled Poly(2-ethyl-2-oxazoline).

PubMed

Glassner, Mathias; Palmieri, Luca; Monnery, Bryn D; Verbrugghen, Thomas; Deleye, Steven; Stroobants, Sigrid; Staelens, Steven; Wyffels, Leonie; Hoogenboom, Richard

2017-01-09

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

Serological reactivity of patients with Echinococcus infections (E. granulosus, E. vogeli, and E. multilocularis) against three antigen B subunits.

PubMed

de la Rue, Mário L; Yamano, Kimiaki; Almeida, Cybele E; Iesbich, Margarete P; Fernandes, Cloé D; Goto, Akiko; Kouguchi, Hirokazu; Takahashi, Kenichi

2010-02-01

In serodiagnosis of cystic echinococcosis (CE) by Echinococcus granulosus infection, antigen B (AgB) has been utilized worldwide. However, it is known that about 40% of sera with alveolar echinococcosis (AE) by Echinococcus multilocularis infection recognize AgB. Furthermore, cross-reaction against AgB was also reported in sera from polycystic echinococcosis (PE) patients with Echinococcus vogeli infection. These findings indicate that AgB is widely common to the genus Echinococcus. On the other hand, AgB has several subunits, which are composed of the smallest 8-kDa subunit. In this study, reactivities of patient sera with three kinds of Echinococcus infections (CE, PE, and AE) were compared simultaneously under the same condition against three subunits of AgB (8, 16, and 24 kDa). Many articles have referred the fundamental 8- kDa subunit as a diagnostic antigen for CE. However, the reactivity for the 8-kDa subunit of the CE patient was not so high (47.7%) in this study. Furthermore, there are many cases in which serum of patients with PE or AE also recognizes this subunit (66.7% in PE; 45.9% in AE). AgB is effective for the detection of the genus Echinococcus infections, but it does not have high species specificity. Therefore, we need to pay attention to cross-reaction in serodiagnosis of CE in areas where plural species coexist.

Teaching Software Componentization: A Bar Chart Java Bean

ERIC Educational Resources Information Center

Mitri, Michel

2010-01-01

In the current object-oriented paradigm, software construction increasingly involves creating and utilizing "software components". These components can serve a variety of functions, from common algorithmic processes to database connectivity to graphical interfaces. The advantage of component architectures is that programmers can use pre-existing…

Analisis del contenido curricular de los Documentos Normativos del Programa de Ciencias en el area de biologia para la escuela superior del sistema de educacion publica de Puerto Rico: 1993-2012

NASA Astrophysics Data System (ADS)

Davila Montanez, Melissa

Esta investigacion de naturaleza cualitativa se ocupo de realizar un analisis de contenido documental de los Documentos Normativos del Programa de Ciencias en el area de biologia de la escuela superior del sistema de educacion publica de Puerto Rico del periodo 1993-2012. Los documentos analizados fueron: Guia Curricular, 1995; Marco Curricular, 2003; Estandares de Excelencia, 1996, 2000 y Estandares de Contenido y Expectativas de Grado, 2007. Se indago si hubo cambios en significados en los Componentes Estructurales: Naturaleza de la ciencia, Paradigmas para la ensenanza de la ciencia, Funcion del curriculo formal, Mision de la ensenanza de la ciencia; Contenidos, destrezas y competencias, Estrategias de ensenanza y Evaluacion/Assessment del aprendizaje. El analisis sugiere que no hubo cambios sustanciales en los significados de los Componentes Estructurales. Los documentos estudiados muestran mayormente caracteristicas similares, aunque los documentos mas recientes eran mas descriptivos, explicativos y especificos.

Teaching astronomy mediated by information and communication technologies: a preliminary approach

NASA Astrophysics Data System (ADS)

Rosa, R. H. L.; Voelzke, M. R.

2014-08-01

O presente trabalho é parte preliminar de um estudo mais amplo em nível de doutorado sobre o ensino de astronomia mediado pelas tecnologias da informação e comunicação, utilizando dispositivos compactos, móveis e pessoais. Este estudo também faz parte do projeto institucional do CEFETMG sobre ambientes diversificados de aprendizagem sob fomento da agência estadual FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais). Esta apresentação aborda o resultado das concepções prévias de estudantes em relação a conhecimentos básicos de astronomia, ligados à percepção e observação direta do céu. Três turmas de estudantes de 1ª série e uma turma de 3ª série do ensino integrado médio técnico da Educação Básica, Técnica e Tecnológica (EBTT) do CEFETMG Campus II - Belo Horizonte/MG foram submetidas a uma avaliação prévia através de questionário estruturado. Este questionário foi elaborado de forma a abordar a percepção dos estudantes em relação aos recursos gráficos (figuras e desenhos) representativos de conhecimentos básicos de astronomia, comuns em livros didáticos. Após a análise dos resultados desta avaliação, organizou-se uma estratégia de intervenção didática em sala de aula sobre o conteúdo de astronomia, utilizando-se de recursos de mediação baseados nas tecnologias da informação e comunicação. Os temas selecionados para esta estratégia didática foram relacionados aos assuntos básicos de astronomia em que ocorreu maior nível de desconhecimento dos estudantes. Os estudantes foram submetidos a avaliação posterior elaborada com os mesmos pressupostos da avaliação prévia. A análise dos resultados foi realizada a partir dos pressupostos da aprendizagem significativa (Ausubel; Novak e Hanesian, 1983). O ensino de astronomia por mediação das tecnologias da informação e comunicação indica uma alternativa preliminar aos trabalhos de campo usuais orientados na prática escolar, tais como, visita a planetários e a observatórios. Os estudantes ficaram muito sensibilizados pela possibilidade de percepção do céu em tempo real e à luz do dia dentro da sala de aula no contexto escolar. Os resultados deste levantamento preliminar indicam que os níveis de ensino fundamental e médio não foram capazes de internalizar conhecimentos básicos de astronomia, a despeito das orientações específicas contidas nos documentos oficiais da educação básica brasileira (Brasil, 1997 e 2000). Os estudantes pesquisados apresentaram conhecimentos e concepções rudimentares sobre o tema astronomia básica, indicando a ausência de abordagem do tema astronomia, tampouco de observação direta do céu em trabalhos de campo escolares na educação básica. Finalmente, esta abordagem didática suscitou nos estudantes grande interesse para futuros trabalhos de observação de campo. D.P. Ausubel; J.D. Novak; H. Hanesian. Psicología Educativa: un punto de vista cognoscitivo. México: Trillas, 1983. BRASIL. Secretaria de Educação Básica. Parâmetros Curriculares Nacionais: Ensino Fundamental (PCN), 1997, e Ensino Médio (PCNEM), 2000. Brasília. MEC/SEB.

Integration of Panda Workload Management System with supercomputers

NASA Astrophysics Data System (ADS)

De, K.; Jha, S.; Klimentov, A.; Maeno, T.; Mashinistov, R.; Nilsson, P.; Novikov, A.; Oleynik, D.; Panitkin, S.; Poyda, A.; Read, K. F.; Ryabinkin, E.; Teslyuk, A.; Velikhov, V.; Wells, J. C.; Wenaus, T.

2016-09-01

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System for managing the workflow for all data processing on over 140 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250000 cores with a peak performance of 0.3+ petaFLOPS, next LHC data taking runs will require more resources than Grid computing can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, Europe and Russia (in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF), Supercomputer at the National Research Center "Kurchatov Institute", IT4 in Ostrava, and others). The current approach utilizes a modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run singlethreaded workloads in parallel on Titan's multi-core worker nodes. This implementation was tested with a variety of Monte-Carlo workloads on several supercomputing platforms. We will present our current accomplishments in running PanDA WMS at supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facility's infrastructure for High Energy and Nuclear Physics, as well as other data-intensive science applications, such as bioinformatics and astro-particle physics.

Analysis of electrocautery generated smoke by chromatographic-mass spectrometry.

PubMed

Kalil, Jefferson; Pessine, Francisco B T; Fidelis, Carlos H V; Menezes, Fabio H; Palma, Paulo Cesar Rodrigues

2016-01-01

to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles. analisar quimicamente os componentes da fumaça do eletrocautério, provenientes da coagulação de tecidos, muscular e hepático de suino. coleta de fumaça produzida por eletrocauterização de tecido porcino em frascos previamente evacuados com análise qualitativa e quantitativa dos compostos presentes, através de técnica hifenada, cromatografia a gás/espectrometria de massas. houve presença majoritária do aldeído decanal nas fumaças provenientes dos tecidos subcutâneo, muscular e hepático. Fumaças dos tecidos subcutâneo e muscular mostraram também a presença de hexanal e fenol. Nas fumaças dos tecidos subcutâneo e hepático foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumaças dos tecidos muscular e hepático. há número crescente de evidências mostrando que fumaça proveniente de eletrocauterização de tecidos subcutâneo, muscular e hepático é nociva à saúde de seres humanos. Portanto, há necessidade de reduzir a exposição a ela ou usar máscara com filtro capaz de reter essas partículas.

Experiences and coping with the altered body image in digestive stoma patients.

PubMed

Hueso-Montoro, César; Bonill-de-Las-Nieves, Candela; Celdrán-Mañas, Miriam; Hernández-Zambrano, Sandra Milena; Amezcua-Martínez, Manuel; Morales-Asencio, José Miguel

2016-12-08

to describe the coping of stoma patients with the news about the ostomy, as well as to analyze the meaning and the experience of their new bodily reality. qualitative phenomenological study undertaken through semistructured interviews with 21 stoma patients. The analysis was based on the constant comparison of the data, the progressive incorporation of subjects and triangulation among researchers and stomal therapy nurses. The software Atlas.ti was used. two main categories emerge: "Coping with the news about receiving a stoma" and "Meaning and experience of the new bodily reality". The informants' answer varies, showing situations that range from the natural acceptance of the process to resignation and rejection. The previous experiences of other family members, the possible reconstruction of the stoma or the type of illness act as conditioning factors. the coping with the news about the stoma is conditioned by the type of illness, although the normalization of the process is the trend observed in most informants. Nursing plays a fundamental role in the implementation of cognitive-behavioral interventions and other resources to promote the patients' autonomy in everything related to care for the stoma. descrever o enfrentamento de pessoas ostomizadas diante da notícia da realização do estoma, assim como analisar o significado e a vivência diante de sua nova realizada corporal. estudo qualitativo fenomenológico mediante entrevistas semiestruturadas com 21 personas ostomizadas. Foi desenvolvido através da comparação constante de dados, incorporação progressiva de sujeitos e triangulação entre investigadores e enfermeiras especialistas em estomaterapia. Foi utilizado o software Atlas.ti. emergiram duas categorias centrais: "Enfrentamento diante da notícia de que serão ostomizados" e "Significado e vivência da nova realidade corporal". A resposta dos informantes é variável, revelando situações que vão desde a aceitação natural do seu processo até a resignação e a rejeição. As experiências prévias de outros familiares, a possibilidade de reconstrução do estoma ou o tipo de doença são fatores condicionantes. o enfrentamento diante da notícia do estoma está condicionado pelo tipo de doença. Apesar disso, observa-se que a maioria dos informantes tende a normalizar o processo. A enfermagem tem papel fundamental na implementação de intervenções cognitivas-comportamentais e outros recursos destinados à promoção da autonomia dos pacientes em tudo relacionado ao cuidado do estoma. describir el afrontamiento de personas ostomizadas ante la noticia de la realización de la ostomía, así como analizar el significado y la vivencia ante su nueva realidad corporal. estudio cualitativo fenomenológico mediante entrevistas semiestructuradas a 21 personas ostomizadas. Se realizó análisis mediante comparación constante de datos, incorporación progresiva de sujetos y triangulación entre investigadores y enfermeras expertas en estomaterapia. Se empleó el programa Atlas.ti. emergen dos categorías centrales: "Afrontamiento ante la noticia de que van a ser ostomizados" y "Significado y vivencia de la nueva realidad corporal". La respuesta de los informantes es variable, percibiéndose situaciones que van desde la aceptación natural de su proceso hasta la resignación y el rechazo. Las experiencias previas de otros familiares, la posibilidad de reconstrucción del estoma o el tipo de enfermedad, son factores condicionantes. el afrontamiento ante la noticia del estoma está condicionado por el tipo de enfermedad, aunque la normalización del proceso es la tendencia observada en la mayoría de los informantes. Enfermería tiene un papel fundamental en la puesta en marcha de intervenciones cognitivos-conductuales y otros recursos destinados a la promoción de la autonomía de los pacientes en todo lo relacionado con el cuidado del estoma.

Changes in frailty conditions and phenotype components in elderly after hospitalization.

PubMed

Marchiori, Gianna Fiori; Tavares, Darlene Mara Dos Santos

2017-07-10

describing the changes in frailty conditions over the period of a year after hospital discharge, verifying predictive variables for changes in frailty conditions and frailty phenotype components according to worsening, improving and stable groups. a longitudinal survey carried out with 129 elderly. A structured form for socioeconomic and health data, scales (Geriatric Depression Scale - short form, Katz scale, Lawton and Brody scale) and frailty phenotype according to Fried were used. Descriptive analysis and multinomial logistic regression model (p<0.05) were performed. we found that 56.7% of older adults changed their condition from non-frail to pre-frail, with no changes from non-frail to frail. Deaths were found between frail and pre-frail elderly. In the worsening group, the increase in the number of morbidities was a predictor for exhaustion and/or fatigue, while in the improving group, increased dependence on instrumental activities of daily living was a predictor for weight loss, and reduced scores indicative of depression due to low level of physical activity. a greater percentage of changes from non-frail condition to pre-frail older adults were observed, and health variables were only predictive for frailty phenotype components. descrever as mudanças nas condições de fragilidade ao longo de um ano após a alta hospitalar, e verificar as variáveis preditoras da mudança das condições de fragilidade e dos componentes do fenótipo de fragilidade, segundo grupos de piora, melhora e estabilidade. inquérito longitudinal, realizado com 129 idosos. Utilizou-se formulário estruturado para dados socioeconômicos e saúde, escalas (Depressão Geriátrica Abreviada, Katz, Lawton e Brody) e fenótipo de fragilidade, segundo Fried. Procederam-se às análises descritiva e modelo de regressão logística multinomial (p<0,05). constatou-se que 56,7% dos idosos mudaram sua condição de não frágeis para pré-frágeis, não ocorrendo mudança dos não frágeis para frágeis. Observou-se o óbito entre idosos frágeis e pré-frágeis. No grupo de piora, o aumento do número de morbidades foi preditor para exaustão e/ou fadiga, enquanto que, no grupo de melhora, o aumento na dependência das atividades instrumentais de vida diária foi preditor para a perda de peso, e a diminuição dos escores do indicativo de depressão para o baixo nível de atividade física. houve maior percentual de mudança na condição de idosos não frágeis para pré-frágeis e as variáveis de saúde foram preditoras apenas para os componentes do fenótipo de fragilidade. describir los cambios en las condiciones de fragilidad a lo largo de un año después del alta hospitalaria, y verificar las variables predictoras del cambio de las condiciones de fragilidad y de los componentes del fenotipo de fragilidad, según grupos de empeoramiento, mejoría y estabilidad. encuesta longitudinal, realizada con 129 ancianos. Se utilizó formulario estructurado para recoger datos socioeconómicos y salud; se utilizaron las escalas Depresión Geriátrica Abreviada (GDS-15), Actividades Básicas de Vida Diaria de Katz, Actividades Instrumentales de Vida Diaria de Lawton y Brody, y Fenotipo de Fragilidad, según Fried. Se procedió al análisis descriptivo y modelo de regresión logística multinomial (p<0,05). se constató que 56,7% de los ancianos cambiaron su condición de no-frágiles para prefrágiles, no habiendo ocurriendo cambio de los no-frágiles para frágiles. Se observó muerte entre ancianos frágiles y prefrágiles. En el grupo de empeoramiento, el aumento del número de morbilidades fue predictor para agotamiento y/o fatiga, en cuanto en el grupo de mejoría, el aumento en la dependencia de las actividades instrumentales de vida diaria fue predictor para la pérdida de peso y la disminución de los puntajes del indicativo de depresión para el bajo nivel de actividad física. hubo mayor porcentaje de cambio en la condición de ancianos no-frágiles para prefrágiles y las variables de salud fueron predictoras apenas para los componentes del fenotipo de fragilidad.

Integration Of PanDA Workload Management System With Supercomputers for ATLAS and Data Intensive Science

DOE Office of Scientific and Technical Information (OSTI.GOV)

De, K; Jha, S; Klimentov, A

2016-01-01

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Managementmore » System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than Grid computing can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, Europe and Russia (in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF), MIRA supercomputer at Argonne Leadership Computing Facilities (ALCF), Supercomputer at the National Research Center Kurchatov Institute , IT4 in Ostrava and others). Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This implementation was tested with a variety of Monte-Carlo workloads on several supercomputing platforms for ALICE and ATLAS experiments and it is in full production for the ATLAS experiment since September 2015. We will present our current accomplishments with running PanDA WMS at supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications, such as bioinformatics and astro-particle physics.« less

Tendências de teses e dissertações sobre ensino de astronomia no Brasil

NASA Astrophysics Data System (ADS)

Bretones, P. S.; Megid Neto, J.

2003-08-01

Neste trabalho são apresentados os resultados de uma pesquisa do tipo estado da arte sobre teses e dissertações defendidas no Brasil e relativas ao ensino de Astronomia. Teve por objetivo identificar essa produção e conhecer as principais tendências da pesquisa nesse campo. O procedimento inicial consistiu de um levantamento bibliográfico junto ao Centro de Documentação em Ensino de Ciências (CEDOC) da Faculdade de Educação da UNICAMP e ao Banco de Teses da CAPES disponível na Internet. Foram localizadas 13 dissertações de mestrado e 3 teses de doutorado, as quais foram estudadas em função dos seguintes aspectos: instituição, ano de defesa, nível escolar abrangido no estudo, foco temático do estudo e gênero de trabalho acadêmico. Deste conjunto de pesquisas, 13 (81,3%) delas foram defendidas a partir da segunda metade dos anos 90, indicando uma preocupação mais recente com temas relativos ao ensino de Astronomia no conjunto da produção acadêmica em programas de pós-graduação no Brasil. Verificou-se que 43,7% dos trabalhos foram produzidas na USP e 18,8% na UNICAMP. Quanto ao nível escolar abrangido nos estudos, predominaram os estudos direcionados ao Ensino Fundamental de 5a a 8a séries (62,5%). No que diz respeito ao foco temático das pesquisas, as principais tendências voltaram-se: 56,3% para Conteúdo e Método; 43,8% para Concepções do Professor; 37,5% para Currículo e Programas; 37,5% para Recursos Didáticos. Quanto ao gênero de trabalho acadêmico, verificou-se que 43,8% são de Pesquisa Experimental e 31,3% de Pesquisa de Análise de Conteúdo. Estudos de revisão bibliográfica como este visam colaborar com a divulgação ampla da produção acadêmica em determinada área, traçando algumas de suas tendências. Ao mesmo tempo possibilita, a partir de investigações decorrentes, apontar as suas contribuições para o ensino e sinalizar com necessidades a serem supridas por futuras pesquisas.

Neuroimaging of the Dopamine/Reward System in Adolescent Drug Use

PubMed Central

Ernst, Monique; Luciana, Monica

2015-01-01

Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana’s interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity. PMID:26095977

Organic Solar Cells: Degradation Processes and Approaches to Enhance Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fungura, Fadzai

2016-12-17

Intrinsic photodegradation of organic solar cells, theoretically attributed to C-H bond rearrangement/breaking, remains a key commercialization barrier. This work presents, via dark electron paramagnetic resonance (EPR), the first experimental evidence for metastable C dangling bonds (DBs) (g=2.0029±0.0004) formed by blue/UV irradiation of polymer:fullerene blend films in nitrogen. The DB density increased with irradiation and decreased ~4 fold after 2 weeks in the dark. The dark EPR also showed increased densities of other spin-active sites in photodegraded polymer, fullerene, and polymer:fullerene blend films, consistent with broad electronic measurements of fundamental properties, including defect/gap state densities. The EPR enabled identification of defectmore » states, whether in the polymer, fullerene, or at the donor/acceptor (D/A) interface. Importantly, the EPR results indicate that the DBs are at the D/A interface, as they were present only in the blend films. The role of polarons in interface DB formation is also discussed.« less

Design and Implementation of Scientific Software Components to Enable Multiscale Modeling: The Effective Fragment Potential (QM/EFP) Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaenko, Alexander; Windus, Theresa L.; Sosonkina, Masha

2012-10-19

The design and development of scientific software components to provide an interface to the effective fragment potential (EFP) methods are reported. Multiscale modeling of physical and chemical phenomena demands the merging of software packages developed by research groups in significantly different fields. Componentization offers an efficient way to realize new high performance scientific methods by combining the best models available in different software packages without a need for package readaptation after the initial componentization is complete. The EFP method is an efficient electronic structure theory based model potential that is suitable for predictive modeling of intermolecular interactions in large molecularmore » systems, such as liquids, proteins, atmospheric aerosols, and nanoparticles, with an accuracy that is comparable to that of correlated ab initio methods. The developed components make the EFP functionality accessible for any scientific component-aware software package. The performance of the component is demonstrated on a protein interaction model, and its accuracy is compared with results obtained with coupled cluster methods.« less

Proficiency training on a virtual reality robotic surgical skills curriculum.

PubMed

Bric, Justin; Connolly, Michael; Kastenmeier, Andrew; Goldblatt, Matthew; Gould, Jon C

2014-12-01

The clinical application of robotic surgery is increasing. The skills necessary to perform robotic surgery are unique from those required in open and laparoscopic surgery. A validated laparoscopic surgical skills curriculum (Fundamentals of Laparoscopic Surgery or FLS™) has transformed the way surgeons acquire laparoscopic skills. There is a need for a similar skills training and assessment tool for robotic surgery. Our research group previously developed and validated a robotic training curriculum in a virtual reality (VR) simulator. We hypothesized that novice robotic surgeons could achieve proficiency levels defined by more experienced robotic surgeons on the VR robotic curriculum, and that this would result in improved performance on the actual daVinci Surgical System™. 25 medical students with no prior robotic surgery experience were recruited. Prior to VR training, subjects performed 2 FLS tasks 3 times each (Peg Transfer, Intracorporeal Knot Tying) using the daVinci Surgical System™ docked to a video trainer box. Task performance for the FLS tasks was scored objectively. Subjects then practiced on the VR simulator (daVinci Skills Simulator) until proficiency levels on all 5 tasks were achieved before completing a post-training assessment of the 2 FLS tasks on the daVinci Surgical System™ in the video trainer box. All subjects to complete the study (1 dropped out) reached proficiency levels on all VR tasks in an average of 71 (± 21.7) attempts, accumulating 164.3 (± 55.7) minutes of console training time. There was a significant improvement in performance on the robotic FLS tasks following completion of the VR training curriculum. Novice robotic surgeons are able to attain proficiency levels on a VR simulator. This leads to improved performance in the daVinci surgical platform on simulated tasks. Training to proficiency on a VR robotic surgery simulator is an efficient and viable method for acquiring robotic surgical skills.

Simplificando a luneta com lente de óculos

NASA Astrophysics Data System (ADS)

Canalle, J. B. G.; de Souza, A. C. F.

2003-08-01

A principal ferramenta de trabalho do astrônomo é o telescópio. O manuseio do mesmo é sempre motivo de enorme curiosidade por parte de alunos do ensino fundamental ou médio e até mesmo dos respectivos professores. Visando propiciar o acesso de alunos e professores ou interessados em geral a uma luneta de fácil construção, com materiais alternativos, de fácil localização no comércio, de baixo custo, resistente ao manuseio de alunos, simplificamos a montagem de uma luneta construída com lente de óculos, de 1 ou 2 graus positivos, e monóculo de fotografia, publicado por este autor no CCEF, vol.11(3), 212, 1994. Esta luneta, a qual permite ver as crateras lunares, apresentava como maior dificuldade de construção o tripé e o local de formação da imagem. Substituímos o tripé de madeira por uma simples garrafa PET de 2 litros cheia d'água. No lugar da ocular usamos a lente do monóculo de fotografia (ou visor de fotografia) encaixado dentro de uma bucha de redução curta, de 40 x 32 mm, e esta não mais dentro de uma luva (conexão hidráulica) de 40 mm de diâmetro, mas sim encostada no próprio tubo de PVC móvel (o qual permite o ajuste do foco) de 40 mm de diâmetro e presa a este por outro tubo de 40 mm de diâmetro e 10 cm de comprimento, serrado ao longo do seu comprimento. Com isto podemos ajustar a posição deste tubo de 10 cm também para que uma das suas extremidades coincida com o local de formação da imagem. Desta forma o observador saberá o local exato da formação da imagem, o que não era evidente na montagem anterior e causava uma dificuldade inicial até se descobrir a posição exata em que se deveria colocar o olho. Deste maneira, a montagem inicial que já era simples ficou ainda mais simples, mais barata e mais confortável para o uso. Um exemplar da mesma será exposto durante a XXIX Reunião Anual da Sociedade Astronômica Brasileira para inspeção e uso dos participantes.

Modelo de Integracion Practica del Componente Educativo en los Planes de Manejo de Emergencia

ERIC Educational Resources Information Center

Martinez Jimenez, Magna M.

2012-01-01

Education is a basic human right for all people, according to the Universal Declaration of Human Rights. Article 22 of the Children's' Rights Convention stipulates that the Nations are obligated to guarantee that any child requesting refuge receive appropriate protection, humanitarian assistance and full enjoyment of all the rights contemplated in…

The Ontological Perspectives of the Semantic Web and the Metadata Harvesting Protocol: Applications of Metadata for Improving Web Search.

ERIC Educational Resources Information Center

Fast, Karl V.; Campbell, D. Grant

2001-01-01

Compares the implied ontological frameworks of the Open Archives Initiative Protocol for Metadata Harvesting and the World Wide Web Consortium's Semantic Web. Discusses current search engine technology, semantic markup, indexing principles of special libraries and online databases, and componentization and the distinction between data and…

Meta-Analysis of Attitudes toward Damage-Causing Mammalian Wildlife

PubMed Central

KANSKY, RUTH; KIDD, MARTIN; KNIGHT, ANDREW T

2014-01-01

Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. Meta-Análisis de las Posturas hacia la Mamíferos Silvestres Causantes de Daños Resumen Muchas poblaciones de mamíferos amenazados persisten fuera de áreas protegidas formales y su supervivencia depende de la buena voluntad de las comunidades que coexisten con ellos. Un entendimiento de las posturas, y específicamente de la tolerancia, de los individuos y las comunidades y los factores que los determinan es fundamental para diseñar estrategias que alivien el conflicto humano – vida silvestre. Llevamos a cabo un meta-análisis para identificar los factores que afectaron las posturas hacia cuatro grupos de mamíferos terrestres. Los elefantes (65%) provocaron las posturas más positivas. Los siguieron los primates (55%), los ungulados (53%) y los carnívoros (44%). Los residentes urbanos presentaron las posturas más positivas (80%), seguidos por los granjeros comerciales (51%) y los granjeros comunales (26%). Un índice de tolerancia a los daños mostró que la tolerancia humana a los ungulados y primates fue proporcional a la probabilidad de experimentar daños mientras que los elefantes provocaron niveles de tolerancia más altos de lo esperado y los carnívoros provocaron niveles de tolerancia más bajos de lo esperado. Contrario a la sabiduría convencional, experimentar daños no fue siempre el factor dominante para determinar las posturas. Los granjeros comunales tuvieron una baja probabilidad de ser positivos hacia los carnívoros independientemente de la probabilidad de experimentar daños, mientras que los granjeros comerciales y los residentes urbanos tuvieron mayor probabilidad de ser positivos hacia los carnívoros independientemente de los daños. Los residentes urbanos tuvieron mayor probabilidad de ser positivos hacia los ungulados, los elefantes y los primates cuando la probabilidad de daños fue baja, pero no cuando fue alta. Los granjeros comerciales y comunales tuvieron una mayor probabilidad de ser positivos hacia los ungulados, los primates y los elefantes independientemente de la probabilidad de experimentar daños. El prejuicio taxonómico por eso puede ser importante. El identificar los distintos factores que explican estas posturas y los contextos específicos en los cuales operan, inclusivo de especies que causan daños, será esencial para priorizar las inversiones en la conservación. PMID:24661270

Telescópio de pequeno porte como suporte ao ensino em cidades com intensa poluição luminosa II

NASA Astrophysics Data System (ADS)

Pereira, P. C. R.; Santos-Júnior, J. M.; Cruz, W. S.

2003-08-01

Para a maioria dos estudantes, sua passagem pelo ensino formal fundamental envolve a transmissão de fatos que devem ser guardados para um exame, a habilidade para lembrar fórmulas e, eventualmente, a repetição de experimentos que devem produzir resultados exigidos pelo professor. O resultado deste modelo de ensino, ao longo dos anos, é conhecido por todos: desconhecimento e descontentamento, por parte dos estudantes, de temas relativos ao papel e aos processos da ciência. Acreditamos que a Astronomia, pelo seu caráter observacional, é uma das áreas do conhecimento que pode contribuir neste cenário. A Fundação Planetário da Cidade do Rio de Janeiro possui um telescópio Meade LX-200 (25cm) que, juntamente com as câmeras CCD ST-7E e ST8E, tem sido utilizado em projetos voltados aos estudantes do ensino médio desde o ano 2000. Tais projetos envolvem a condução de um projeto de pesquisa observacional num nível apropriado, e possibilitam o contato com técnicas e novas tecnologias: computador, software para manipulação de dados e gráficos, programas de tratamento e redução de dados, uso de equipamentos óptico-eletrônicos (telescópio e CCD), bem como o processo de aquisição de conhecimento. Dentro da proposta dos anos anteriores, priorizamos projetos de uma noite, ou seja, procuramos trabalhar com fenômenos que apresentem variabilidade com intervalo de recorrência relativamente curto. Em todos os casos, optamos pela fotometria diferencial, que tem se mostrado bastante eficiente para o céu luminoso como o da cidade do Rio de Janeiro. Neste painel, apresentamos alguns dos projetos desenvolvidos no último ano, com 25 estudantes. Apresentamos os resultados da observação da variável pulsante AI Vel (V = 6,6) e da variável cataclísmica FO Aqr (V = 13,5), e do monitoramento do trânsito da lua de Júpiter, Europa, ocorrido em 30 de abril de 2003. As curvas de luz produzidas para as primeiras estão concordantes com as da literatura, assim como os respectivos períodos encontrados (1h20min e 4h48min). No caso do FO Aqr, ficou evidente, também, a modulação decorrente da rotação da anã branca receptora (21min). O erro estimado é de 0,01 magnitude. Propomos uma maior utilização de telescópios de pequeno porte, como suporte ao ensino (médio e superior) em cidades com poluição luminosa. Escolas e Planetários seriam ambientes propícios para a localização do telescópio. Os critérios adotados na escolha dos objetos e o método observacional empregado são também apresentados.

Characterisation of fucoidan extracted from Malaysian Sargassum binderi.

PubMed

Lim, Seng Joe; Wan Aida, Wan Mustapha; Maskat, Mohamad Yusof; Latip, Jalifah; Badri, Khairiah Haji; Hassan, Osman; Yamin, Bohari M

2016-10-15

Fucoidan is a sulphated polysaccharide that consists mainly of fucose, normally found in brown seaweeds. In this study, fucoidan was extracted from Sargassum binderi (Fsar) from Malaysia and subsequently characterised. The chemical characteristics of Fsar were found to be different than those of commercial food grade fucoidan (Fysk) and those of previously studied fucoidans. NMR analysis proposed that the main structure of Fsar is →3)fuc-2-OSO3(-)(1→3)fuc(1→. The molecular weight (47.87kDa) and degree of sulphation (0.20) of Fsar were higher than those of Fysk, at 27.98kDa and 0.15, respectively. However, Fsar's polydispersity index (1.12) and fucose content (34.50%) were lower than those of Fysk, at 1.88 and 43.30%, respectively. Both Fsar and Fysk showed similar thermo-gravimetric properties with four mass losses, amorphous in nature and negative optical rotations. Results show that Fsar has fundamental characteristics of fucoidan with different structural conformation i.e. variation in glycosidic linkages and sulphate group orientation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Melhoramentos no código Wilson-Devinney para binárias eclipsantes

NASA Astrophysics Data System (ADS)

Vieira, L. A.; Vaz, L. P. R.

2003-08-01

A análise de curvas de luz e velocidades radiais de sistemas binários eclipsantes pode ser feita por meio de vários modelos. Um desses é o Modelo Wilson-Devinney (WD). Ao longo dos anos, esse modelo sofreu várias alterações em seus códigos principais, com a finalidade de torná-lo mais consistente tanto fíisica como numericamente. O Modelo WD tem sido melhorado de várias maneiras em seus dois códigos: um para a predição das curvas de luz teórica e de velocidade radiais e outra para as soluções destas curvas. Teoricamente, na física do modelo, nós introduzimos a possibilidade de levar em conta os efeitos do movimento apsidal. Numericamente, nós introduzimos a possibilidade de usar o Método SIMPLEX no procedimento da solução, como uma alternativa para o já implementado Método de Mínimos Quadrados (Least Squares Method). Estas modificações, juntamente com outras já introduzidas pelo nosso grupo anteriormente, tornam o código mais eficiente na solução das curvas de luz e de velocidade radiais de binárias eclipsantes. Como o modelo tem sido usado para analisar sistemas com componentes pré-sequência principal (TY CrA, Casey et al. 1998, Vaz et al. 1998), SM 790, Stassun et al. 2003), este melhoramento beneficiará estes casos também. Apresentamos os resultados obtidos com a modificação do código WD por meio do uso de dados da estrela GL Carinae, comprovando, (1) que os parâmetros orbitais calculados por nós são coerentes com os obtidos anteriormente na literatura (Giménez & Clausen, 1986) e com os obtidos por Faria (1987), e (2) que a implementação do Método SIMPLEX torna o código mais lento mas completamente consistente internamente e evita os problemas gerados pelo uso do Método de Mínimos Quadrados, tais como imprecisão no cálculo das derivadas parciais e convergência para mínimos locais.

NASDA's view of ground control in mission operations

NASA Technical Reports Server (NTRS)

Tateno, Satoshi

1993-01-01

This paper presents an overview of the present status and future plans of the National Space Development Agency of Japan 's (NASDA's) ground segment and related space missions. The described ground segment consists of the tracking and data acquisition (T&DA) system and the Earth Observation Center (EOC) system. In addition to these systems, the current plan of the Engineering Support Center (ESC) for the Japanese Experiment Module (JEM) attached to Space Station Freedom is introduced. Then, NASDA's fundamental point of view on the future trend of operations and technologies in the coming new space era is discussed. Within the discussion, the increasing importance of international cooperation is also mentioned.

Modelo analítico del efecto de PRS sobre satélites GPS

NASA Astrophysics Data System (ADS)

Meza, A.; Brunini, C.; Usandivaras, J. C.

El sistema GPS (Global Position System) es, hoy en día, la herramienta de navegación y posicionamiento más potente y lo será sin duda en la próxima década. Gran parte de su valiosa utilidad se debe a la alta precisión que permite lograr y ésta, a su vez, depende, entre otras causas, de la precisión con que se conocen las órbitas de los satélites. La presión de radiación solar (PRS) fija el límite de la precisión con que pueden calcularse en la actualidad las efemérides satelitarias. El objetivo de este trabajo es proponer una mejor resolución de este fenómeno. El modelo analítico aquí presentado, se basa en el análisis del comportamiento de los residuos de un ajuste por mínimos cuadrados en el que se utiliza el modelo de PRS propuesto por Beutler. El mismo consiste en un modelo determinista del fenómeno con dos parámetros libres. Los resultados obtenidos ponen de manifiesto que, aún después de aplicar dichos parámetros, prevalecen en los residuos efectos semidiurnos en las componentes radial,tangencial y normal. Estos resultados obtenidos se comparan con los de un trabajo desarrollado por el Instituto de Berne (Beutler et al., 1994), en el que se utilizaron como pseudo-observaciones las órbitas precisas del IGS (CODE). El intervalo de integración escogido por este centro fueron las semanas 680 y 681. En resumen se tienen arcos de 14 días para todos los satélites, donde las efemérides precisas de los mismos para los 14 días fueron utilizados como pseudo-observaciones. El modelo de fuerza que empleó dicho centro fue básicamente el tradicional en lo que respecta al modelo de las fuerzas gravitacionales, y para la PRS utilizo el modelo standard de Beutler. Los parámetros de este modelo junto con las 6 condiciones iniciales (posición y velocidad) fueron ajustados por el método general de mínimos cuadrados. Los residuos en la componente radial, tangencial y normal, para los satélites con un buen comportamiento, presentan una componente semidiurna. El modelo analítico planteado en este trabajo, predice el comportamiento de los residuos que se observan en las publicaciones más recientes. Esto abre el camino para plantear una estimación distinta de las incógnitas del problema, basado en el método de colocación por mínimos cuadrados. Ello requiere modelar estadísticamente la señal debida a las componentes de la PRS que no son tomadas en cuenta en el modelo determinista.

Quantitative control of poly(ethylene oxide) surface antifouling and biodetection through azimuthally enhanced grating coupled-surface plasmon resonance sensing

NASA Astrophysics Data System (ADS)

Sonato, Agnese; Silvestri, Davide; Ruffato, Gianluca; Zacco, Gabriele; Romanato, Filippo; Morpurgo, Margherita

2013-12-01

Grating Coupled-Surface Plasmon reflectivity measurements carried out under azimuth and polarization control (GC-SPR φ ≠ 0°) were used to optimize the process of gold surface dressing with poly(ethylene oxide) (PEO) derivatives of different molecular weight, with the final goal to maximize the discrimination between specific and non-specific binding events occurring at the surface. The kinetics of surface deposition of thiol-ending PEOs (0.3, 2 and 5 kDa), introduced as antifouling layers, was monitored. Non-specific binding events upon immersion of the surfaces into buffers containing either 0.1% bovine serum albumin or 1% Goat Serum, were evaluated as a function of polymer size and density. A biorecognition event between avidin and biotin was then monitored in both buffers at selected low and high polymer surface densities and the contribution of analyte and fouling elements to the signal was precisely quantified. The 0.3 kDa PEO film was unable to protect the surface from non-specific interactions at any tested density. On the other hand, the 2 and 5 kDa polymers at their highest surface densities guaranteed full protection from non-specific interactions from both buffers. These densities were reached upon a long deposition time (24-30 h). The results pave the way toward the application of this platform for the detection of low concentration and small dimension analytes, for which both non-fouling and high instrumental sensitivity are fundamental requirements.

Optimization of NMR spectroscopy of encapsulated proteins dissolved in low viscosity fluids

PubMed Central

Nucci, Nathaniel V.; Marques, Bryan S.; Bédard, Sabrina; Dogan, Jakob; Gledhill, John M.; Moorman, Veronica R.; Peterson, Ronald W.; Valentine, Kathleen G.; Wand, Alison L.; Wand, A. Joshua

2014-01-01

Comprehensive application of solution NMR spectroscopy to studies of macromolecules remains fundamentally limited by the molecular rotational correlation time. For proteins, molecules larger than 30 kDa require complex experimental methods, such as TROSY in conjunction with isotopic labeling schemes that are often expensive and generally reduce the potential information available. We have developed the reverse micelle encapsulation strategy as an alternative approach. Encapsulation of proteins within the protective nano-scale water pool of a reverse micelle dissolved in ultra-low viscosity nonpolar solvents overcomes the slow tumbling problem presented by large proteins. Here, we characterize the contributions from the various components of the protein-containing reverse micelle system to the rotational correlation time of the encapsulated protein. Importantly, we demonstrate that the protein encapsulated in the reverse micelle maintains a hydration shell comparable in size to that seen in bulk solution. Using moderate pressures, encapsulation in ultra-low viscosity propane or ethane can be used to magnify this advantage. We show that encapsulation in liquid ethane can be used to reduce the tumbling time of the 43 kDa maltose binding protein from ~23 ns to ~10 ns. These conditions enable, for example, acquisition of TOCSY-type data resolved on the adjacent amide NH for the 42 kDa encapsulated maltose binding protein dissolved in liquid ethane, which is typically impossible for proteins of such size without use of extensive deuteration or the TROSY effect. PMID:21748265

Anti-Yo antibody uptake and interaction with its intracellular target antigen causes Purkinje cell death in rat cerebellar slice cultures: a possible mechanism for paraneoplastic cerebellar degeneration in humans with gynecological or breast cancers.

PubMed

Greenlee, John E; Clawson, Susan A; Hill, Kenneth E; Wood, Blair; Clardy, Stacey L; Tsunoda, Ikuo; Carlson, Noel G

2015-01-01

Anti-Yo antibodies are immunoglobulin G (IgG) autoantibodies reactive with a 62 kDa Purkinje cell cytoplasmic protein. These antibodies are closely associated with paraneoplastic cerebellar degeneration in the setting of gynecological and breast malignancies. We have previously demonstrated that incubation of rat cerebellar slice cultures with patient sera and cerebrospinal fluid containing anti-Yo antibodies resulted in Purkinje cell death. The present study addressed three fundamental questions regarding the role of anti-Yo antibodies in disease pathogenesis: 1) Whether the Purkinje cell cytotoxicity required binding of anti-Yo antibody to its intraneuronal 62 kDa target antigen; 2) whether Purkinje cell death might be initiated by antibody-dependent cellular cytotoxicity rather than intracellular antibody binding; and 3) whether Purkinje cell death might simply be a more general result of intracellular antibody accumulation, rather than of specific antibody-antigen interaction. In our study, incubation of rat cerebellar slice cultures with anti-Yo IgG resulted in intracellular antibody binding, and cell death. Infiltration of the Purkinje cell layer by cells of macrophage/microglia lineage was not observed until extensive cell death was already present. Adsorption of anti-Yo IgG with its 62 kDa target antigen abolished both antibody accumulation and cytotoxicity. Antibodies to other intracellular Purkinje cell proteins were also taken up by Purkinje cells and accumulated intracellularly; these included calbindin, calmodulin, PCP-2, and patient anti-Purkinje cell antibodies not reactive with the 62 kDa Yo antigen. However, intracellular accumulation of these antibodies did not affect Purkinje cell viability. The present study is the first to demonstrate that anti-Yo antibodies cause Purkinje cell death by binding to the intracellular 62 kDa Yo antigen. Anti-Yo antibody cytotoxicity did not involve other antibodies or factors present in patient serum and was not initiated by brain mononuclear cells. Purkinje cell death was not simply due to intraneuronal antibody accumulation.

Anti-Yo Antibody Uptake and Interaction with Its Intracellular Target Antigen Causes Purkinje Cell Death in Rat Cerebellar Slice Cultures: A Possible Mechanism for Paraneoplastic Cerebellar Degeneration in Humans with Gynecological or Breast Cancers

PubMed Central

Greenlee, John E.; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Clardy, Stacey L.; Tsunoda, Ikuo; Carlson, Noel G.

2015-01-01

Anti-Yo antibodies are immunoglobulin G (IgG) autoantibodies reactive with a 62 kDa Purkinje cell cytoplasmic protein. These antibodies are closely associated with paraneoplastic cerebellar degeneration in the setting of gynecological and breast malignancies. We have previously demonstrated that incubation of rat cerebellar slice cultures with patient sera and cerebrospinal fluid containing anti-Yo antibodies resulted in Purkinje cell death. The present study addressed three fundamental questions regarding the role of anti-Yo antibodies in disease pathogenesis: 1) Whether the Purkinje cell cytotoxicity required binding of anti-Yo antibody to its intraneuronal 62 kDa target antigen; 2) whether Purkinje cell death might be initiated by antibody-dependent cellular cytotoxicity rather than intracellular antibody binding; and 3) whether Purkinje cell death might simply be a more general result of intracellular antibody accumulation, rather than of specific antibody-antigen interaction. In our study, incubation of rat cerebellar slice cultures with anti-Yo IgG resulted in intracellular antibody binding, and cell death. Infiltration of the Purkinje cell layer by cells of macrophage/microglia lineage was not observed until extensive cell death was already present. Adsorption of anti-Yo IgG with its 62 kDa target antigen abolished both antibody accumulation and cytotoxicity. Antibodies to other intracellular Purkinje cell proteins were also taken up by Purkinje cells and accumulated intracellularly; these included calbindin, calmodulin, PCP-2, and patient anti-Purkinje cell antibodies not reactive with the 62 kDa Yo antigen. However, intracellular accumulation of these antibodies did not affect Purkinje cell viability. The present study is the first to demonstrate that anti-Yo antibodies cause Purkinje cell death by binding to the intracellular 62 kDa Yo antigen. Anti-Yo antibody cytotoxicity did not involve other antibodies or factors present in patient serum and was not initiated by brain mononuclear cells. Purkinje cell death was not simply due to intraneuronal antibody accumulation. PMID:25885452

Do the Constants of Nature Couple to Strong Gravitational Fields?

NASA Astrophysics Data System (ADS)

Preval, Simon P.; Barstow, Martin A.; Holberg, Jay B.; Barrow, John; Berengut, Julian; Webb, John; Dougan, Darren; Hu, Jiting

2015-06-01

Recently, white dwarf stars have found a new use in the fundamental physics community. Many prospective theories of the fundamental interactions of Nature allow traditional constants, like the fine structure constant α, to vary in some way. A study by Berengut et al. (2013) used the Fe/Ni v line measurements made by Preval et al. (2013) from the hot DA white dwarf G191-B2B, in an attempt to detect any variation in α. It was found that the Fe v lines indicated an increasing alpha, whereas the Ni v lines indicated a decreasing alpha. Possible explanations for this could be misidentification of the lines, inaccurate atomic data, or wavelength dependent distortion in the spectrum. We examine the first two cases by using a high S/N reference spectrum from the hot sdO BD+28°4211 to calibrate the Fe/Ni v atomic data. With this new data, we re-evaluate the work of Berengut et al. (2013) to derive a new constraint on the variation of alpha in a gravitational field.

The Practice of Research of a Basic Education Teacher Involving Mental Models of the Phases of the Moon and Eclipses. (Spanish Title: La Práctica de Investigación de un Maestro de Educación BÁsica con El Uso de los Modelos Mentales de Las Fases de la Luna Y Eclipses.) A Prática de Pesquisa de um Professor do Ensino Fundamental Envolvendo Modelos Mentais de Fases da Lua e Eclipses

NASA Astrophysics Data System (ADS)

Pessôa Queiroz, Glória; Jubitipan Borges de Sousa, Carlos; Auxiliadora Delgado Machado, Maria

2009-12-01

The inclusion of basic education teachers in the survey domain is a controversial issue and fully debated in the academy. The opportunity for a collective work that incorporated school teachers from a public school to a university's group of physics teaching at university allowed us to glimpse the redefinition of the function of a science teacher (a coauthor of this paper) by himself, such that now he includes research on the knowledge construction by students in his teacher practice. The formation of inter-institutional groups for action planning and research in these areas has proved productive for the task of knowledge construction to support educational processes in school, while the university enriches its collection of experiences critically validated, and can consider the results in teachers initial and continued education. The active participation of the teacher in a research group at the university led him to reflect on the possible didactical ways to be described, analyzed and communicated to other teachers. The construction of a pedagogy that took into account the mental models of students on the basic topics of astronomy, and the changes developed resulting from the lessons taught, led to far-reaching consequences on the pedagogy adopted by the teacher, who incorporates now a new vision of science and alternative forms to dialogue with students, essential components for a researcher in Science Education. La inclusión de los maestros de la escuela básica en el universo de la investigación es polémica y está en amplio debate en el mundo académico. La oportunidad de trabajo colectivo de los maestros de una escuela pública en Río de Janeiro con un grupo universitario de enseñanza de la física nos ha permitido vislumbrar la redefinición de la función de un maestro de ciencias (uno de los coautores de este documento) por él mismo, ahora para incluir la investigación sobre la construcción del conocimiento por los alumnos en su práctica como docente. La formación de grupos interinstitucionales para la planificación de la acción y la investigación ha resultado productiva para el trabajo de construcción de conocimiento de apoyo a los procesos educativos en la escuela, mientras que la universidad enriquece su colección de experiencias validadas, considerando los resultados de la educación inicial y continua de maestros. La participación activa del maestro en un grupo de investigación en la universidad lo llevó a reflexiones sobre los posibles caminos didácticos que pueden ser descriptos, analizados y comunicados a los demás docentes. La construcción de una pedagogía propia, que tuvo en cuenta los modelos mentales de los estudiantes sobre los temas básicos de astronomía, y los cambios desarrollados a partir de las lecciones que enseñó, trajeron consecuencias de largo alcance sobre la pedagogía adoptada por el maestro, que ahora incorpora una nueva visión de la ciencia y formas alternativas al diálogo con los estudiantes, los componentes esenciales para un investigador en Educaciónen Ciencias. A inclusão do professor da escola básica no universo da pesquisa é questão controvertida e em pleno debate no meio acadêmico. A oportunidade de trabalho coletivo que incorporou professores de uma escola municipal no Rio de Janeiro a um grupo de ensino de Física da universidade nos possibilitou vislumbrar a ressignificação da função de um professor de Ciências (co-autor deste trabalho) por ele próprio, agora passando a incluir a pesquisa sobre a construção de conhecimento pelos alunos em sua prática como docente. A formação de grupos interinstitucionais para o planejamento de ações e de pesquisas tem-se mostrado produtiva para um trabalho de construção de conhecimentos a fim de subsidiar processos educativos na escola, ao mesmo tempo em que a universidade enriquece seu acervo de experiências validadas criticamente, podendo considerar seus resultados na formação inicial e continuada de professores. A participação ativa do professor num grupo de pesquisa na universidade o levou à reflexão sobre caminhos didáticos possíveis de serem descritos, analisados e comunicados a outros professores. A construção de uma pedagogia própria, levando em conta os modelos mentais dos alunos sobre temas básicos de Astronomia, e as mudanças promovidas a partir das aulas dadas, trouxeram amplas conseqüências sobre a pedagogia adotada pelo professor. Hoje a prática desse professor incorpora uma nova visão de ciência e formas alternativas de dialogar com os alunos, elementos indispensáveis a um pesquisador em Educação em Ciências.

Minimum Map of Social Institutional Network: a multidimensional strategy for research in Nursing.

PubMed

Carlos, Diene Monique; Pádua, Elisabete Matallo Marchesini de; Nakano, Ana Márcia Spanó; Ferriani, Maria das Graças Carvalho

2016-06-01

To analyze the use of methodological strategies in qualitative research - Minimum Maps of Social Institutional Network, as proposed to understand the phenomena in the multidimensional perspective. Methodological theoretical essay in which we aimed to reflect on the use of innovative methodological strategies in nursing research, supported in Complex Paradigm fundamentals. The minimum map of Social Institutional External Network aims to identify institutional linkages and gaps for the intervention work of the surveyed institutions. The use of these maps provided important advances in know-how qualitative research in Health and Nursing. In this perspective, the use of minimum Social Intitutional Network maps can be stimulated and enhanced to meet the current demands of the contemporary world, particularly for its flexibility in adapting to various research subjects; breadth and depth of discussion; and possibilities with health services. Analisar o uso de estratégias metodológicas em pesquisas qualitativas - Mapa mínimo da Rede Social Institucional, como proposta para compreender os fenômenos na perspectiva multidimensional. Ensaio teórico metodológico em que buscou-se refletir sobre o uso de estratégias metodológicas inovadoras de pesquisa na enfermagem, sustentada nos fundamentos do Pensamento Complexo. O mapa mínimo da Rede Social Institucional Externa tem o objetivo de identificar os vínculos institucionais e lacunas para o trabalho de intervenção das instituições pesquisadas. O uso destes mapas proporcionou avanços importantes no saber-fazer pesquisa qualitativa em Saúde e Enfermagem. Nessa perspectiva, o uso de mapas mínimos da Rede Social Institucional pode ser estimulado e potencializado para responder às atuais demandas da contemporaneidade, em especial pela sua flexibilidade na adequação a diversos objetos de pesquisa; amplitude e profundidade de discussão; e possibilidades de articulação com a prática dos serviços.

Polymeric amphiphile branching leads to rare nanodisc shaped planar self-assemblies.

PubMed

Qu, Xiaozhong; Omar, Leila; Le, Thi Bich Hang; Tetley, Laurence; Bolton, Katherine; Chooi, Kar Wai; Wang, Wei; Uchegbu, Ijeoma F

2008-09-16

Self-assembly is fundamental to the biological function of cells and the fabrication of nanomaterials. However, the origin of the shape of various self-assemblies, such as the shape of cells, is not altogether clear. Polymeric, oligomeric, or low molecular weight amphiphiles are a rich source of nanomaterials, and controlling their self-assembly is the route to tailored nanosystems with specific functionalities. Here, we provide direct evidence that a particular molecular architecture, polymeric branching, leads to a rare form of self-assembly, the planar nanodisc. Cholesterol containing self-assemblies formed from amphiphilic linear or branched cetyl poly(ethylenimine) (Mn approximately 1000 Da) or amphiphilic cetyl poly(propylenimine) dendrimer derivatives (Mn approximately 2000 Da) show that branching, by reducing the hydrophilic headgroup area, alters the shape of the self-assemblies transforming closed 60 nm spherical bilayer vesicles to rare 50 nm x 10 nm planar bilayer discs. Increasing the hydrophilic headgroup area, by the inclusion of methoxy poly(ethylene glycol) moieties into the amphiphilic headgroup, transforms the planar discs to 100 nm spherical bilayer vesicles. This study provides insight into the key role played by molecular shape on molecular self-organization into rare nanodiscs.

Ayurvĕda gleaned through Buddhism.

PubMed

Narayana, Ala; Lavekar, G S

2005-01-01

The Păli canon consists of three Pitakas (baskets), which replete the Buddhism and is known as Tripiţaka, viz, Vinaya, Sutta and Abhidhamma Piţakas. The original phase of Tripiţaka (Buddhisim started in 544 B.C. and lastly systematized up to 29 B.C. The Buddhist literature also possesses the esoteric material of Medical Science, which is practiced and conserved in India since centuries. It refers to the fundamentals of medicine, rules of good living, which lay considerable emphasis on the hygiene of body, mind. Internal Medicine, curative medicine including symptoms, methods of diagnosis, theories of causation, materia-medica, therapeutics and treatment and skills of Jivaka. Some famous and popular prescriptions are also dealt with.

Soil Moisture Data Assimilation in the NASA Land Information System for Local Modeling Applications and Improved Situational Awareness

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; Blakenship, Clay B.; Zavodsky, Bradley T.

2014-01-01

As part of the NASA Soil Moisture Active Passive (SMAP) Early Adopter (EA) program, the NASA Shortterm Prediction Research and Transition (SPoRT) Center has implemented a data assimilation (DA) routine into the NASA Land Information System (LIS) for soil moisture retrievals from the European Space Agency's Soil Moisture Ocean Salinity (SMOS) satellite. The SMAP EA program promotes application-driven research to provide a fundamental understanding of how SMAP data products will be used to improve decision-making at operational agencies. SPoRT has partnered with select NOAA/NWS Weather Forecast Offices (WFOs) that use output from a real-time regional configuration of LIS, without soil moisture DA, to initialize local numerical weather prediction (NWP) models and enhance situational awareness. Improvements to local NWP with the current LIS have been demonstrated; however, a better representation of the land surface through assimilation of SMOS (and eventually SMAP) retrievals is expected to lead to further model improvement, particularly during warm-season months. SPoRT will collaborate with select WFOs to assess the impact of soil moisture DA on operational forecast situations. Assimilation of the legacy SMOS instrument data provides an opportunity to develop expertise in preparation for using SMAP data products shortly after the scheduled launch on 5 November 2014. SMOS contains a passive L-band radiometer that is used to retrieve surface soil moisture at 35-km resolution with an accuracy of 0.04 cu cm cm (exp -3). SMAP will feature a comparable passive L-band instrument in conjunction with a 3-km resolution active radar component of slightly degraded accuracy. A combined radar-radiometer product will offer unprecedented global coverage of soil moisture at high spatial resolution (9 km) for hydrometeorological applications, balancing the resolution and accuracy of the active and passive instruments, respectively. The LIS software framework manages land surface model (LSM) simulations and includes an Ensemble Kalman Filter for conducting land surface DA. SPoRT has added a module to read, quality-control and bias-correct swaths of Level II SMOS soil moisture retrievals prior to assimilation within LIS. The impact of SMOS DA is being tested using the Noah LSM. Experiments are being conducted to examine the impacts of SMOS soil moisture DA on the resulting LISNoah fields and subsequent NWP simulations using the Weather Research and Forecasting (WRF) model initialized with LIS-Noah output. LIS-Noah soil moisture will be validated against in situ observations from Texas A&M's North American Soil Moisture Database to reveal the impact and possible improvement in soil moisture trends through DA. WRF model NWP case studies will test the impacts of DA on the simulated near-surface and boundary-layer environments, and precipitation during both quiescent and disturbed weather scenarios. Emphasis will be placed on cases with large analysis increments, especially due to contributions from regional irrigation patterns that are not represented by precipitation input in the baseline LIS-Noah run. This poster presentation will describe the soil moisture DA methodology and highlight LIS-Noah and WRF simulation results with and without assimilation.

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

PubMed Central

Mazzio, Elizabeth A.; Close, Fran; Soliman, Karam F.A.

2011-01-01

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible. PMID:21340000

High Speed Intact Protein Characterization Using 4X Frequency Multiplication, Ion Trap Harmonization, and 21 Tesla FTICR-MS.

PubMed

Shaw, Jared B; Gorshkov, Mikhail V; Wu, Qinghao; Paša-Tolić, Ljiljana

2018-05-01

Mass spectrometric characterization of large biomolecules, such as intact proteins, requires the specificity afforded by ultrahigh resolution mass measurements performed at both the intact mass and product ion levels. Although the performance of time-of-flight mass analyzers is steadily increasing, the choice of mass analyzer for large biomolecules (e.g., proteins >50 kDa) is generally limited to the Fourier transform family of mass analyzers such as Orbitrap and ion cyclotron resonance (FTICR-MS), with the latter providing unmatched mass resolving power and measurement accuracy. Yet, protein analyses using FTMS are largely hindered by the low acquisition rates of spectra with ultrahigh resolving power. Frequency multiple detection schemes enable FTICR-MS to overcome this fundamental barrier and achieve resolving powers and acquisition speeds 4× greater than the limits imposed by magnetic field strength. Here we expand upon earlier work on the implementation of this technique for biomolecular characterization. We report the coupling of 21T FTICR-MS, 4X frequency multiplication, ion trapping field harmonization technology, and spectral data processing methods to achieve unprecedented acquisition rates and resolving power in mass spectrometry of large intact proteins. Isotopically resolved spectra of multiply charged ubiquitin ions were acquired using detection periods as short as 12 ms. Large proteins such as apo-transferrin (MW = 78 kDa) and monoclonal antibody (MW = 150 kDa) were isotopically resolved with detection periods of 384 and 768 ms, respectively. These results illustrate the future capability of accurate characterization of large proteins on time scales compatible with online separations.

Magnetic Reconnection and the Kelvin-Helmholtz Instability

NASA Astrophysics Data System (ADS)

Knoll, D. A.; Chacon, L.; Brackbill, J. U.; Lapenta, G.

2002-11-01

Results are presented from a continuing study of magnetic reconnection caused by the evolution of a Kelvin-Helmholtz instability. To date we have studied 3-D compressible, subsonic and and sub-Alfvenic flow, with differential rotation (a gradient in vorticity parallel to the initial magnetic field) [1,2], as well as 2-D incompressible super-Alfvenic flow [3]. In both cases localized transient reconnection is observed on the Kelvin-Helmholtz time scale, and results indicate that the observed reconnection rate is insensitive to resistivity. In the present study we extend both the 2-D and the 3-D results found in [1,2,3]. In the extension of the 2-D work we focus on the fundamental differences in the nonlinear evolution of a low S simulation (S = 200) and a higher S simulation (S = 10,000). In the 3-D work we study the effects of a density discontinuity (present in [1] and not in [2]), along with study the effects of initial curved field lines in the absence of differential rotation. This basic plasma physics problem has possible application to dayside magnetosphere reconnection as a theoretical model for flux transfer events [1]. The general problem also has possible application to solar physics as it could provide a trigger mechanism for some class of coronal mass ejections. Both applications will be briefly discussed. [1] J.U. Brackbill and D.A. Knoll, Phys. Rev. Lett., vol. 86 (2001). [2] D.A. Knoll and J.U. Brackbill, Physics of Plasmas, to appear (2002) [3] D.A. Knoll and L. Chacon, Phys. Rev. Lett., vol. 88 (2002).

Vault-poly-ADP-ribose polymerase in the Octopus vulgaris brain: a regulatory factor of actin polymerization dynamic.

PubMed

De Maio, Anna; Natale, Emiliana; Rotondo, Sergio; Di Cosmo, Anna; Faraone-Mennella, Maria Rosaria

2013-09-01

Our previous behavioural, biochemical and immunohistochemical analyses conducted in selected regions (supra/sub oesophageal masses) of the Octopus vulgaris brain detected a cytoplasmic poly-ADP-ribose polymerase (more than 90% of total enzyme activity). The protein was identified as the vault-free form of vault-poly-ADP-ribose polymerase. The present research extends and integrates the biochemical characterization of poly-ADP-ribosylation system, namely, reaction product, i.e., poly-ADP-ribose, and acceptor proteins, in the O. vulgaris brain. Immunochemical analyses evidenced that the sole poly-ADP-ribose acceptor was the octopus cytoskeleton 50-kDa actin. It was present in both free, endogenously poly-ADP-ribosylated form (70kDa) and in complex with V-poly-ADP-ribose polymerase and poly-ADP-ribose (260kDa). The components of this complex, alkali and high salt sensitive, were purified and characterized. The kind and the length of poly-ADP-ribose corresponded to linear chains of 30-35 ADP-ribose units, in accordance with the features of the polymer synthesized by the known vault-poly-ADP-ribose polymerase. In vitro experiments showed that V-poly-ADP-ribose polymerase activity of brain cytoplasmic fraction containing endogenous actin increased upon the addition of commercial actin and was highly reduced by ATP. Anti-actin immunoblot of the mixture in the presence and absence of ATP showed that the poly-ADP-ribosylation of octopus actin is a dynamic process balanced by the ATP-dependent polymerization of the cytoskeleton protein, a fundamental mechanism for synaptic plasticity. © 2013 Elsevier Inc. All rights reserved.

Poly(glycidyl ether)-Based Monolayers on Gold Surfaces: Control of Grafting Density and Chain Conformation by Grafting Procedure, Surface Anchor, and Molecular Weight.

PubMed

Heinen, Silke; Weinhart, Marie

2017-03-07

For a meaningful correlation of surface coatings with their respective biological response reproducible coating procedures, well-defined surface coatings, and thorough surface characterization with respect to layer thickness and grafting density are indispensable. The same applies to polymeric monolayer coatings which are intended to be used for, e.g., fundamental studies on the volume phase transition of surface end-tethered thermoresponsive polymer chains. Planar gold surfaces are frequently used as model substrates, since they allow a variety of straightforward surface characterization methods. Herein we present reproducible grafting-to procedures performed with thermoresponsive poly(glycidyl ether) copolymers composed of glycidyl methyl ether (GME) and ethyl glycidyl ether (EGE). The copolymers feature different molecular weights (2 kDa, 9 kDa, 24 kDa) and are equipped with varying sulfur-containing anchor groups in order to achieve adjustable grafting densities on gold surfaces and hence control the tethered polymers' chain conformation. We determined "wet" and "dry" thicknesses of these coatings by QCM-D and ellipsometry measurements and deduced anchor distances and degrees of chain overlap of the polymer chains assembled on gold. Grafting under cloud point conditions allowed for higher degrees of chain overlap compared to grafting from a good solvent like ethanol, independent of the used sulfur-containing anchor group for polymers with low (2 kDa) and medium (9 kDa) molecular weights. By contrast, the achieved grafting densities and thus chain overlaps of surface-tethered polymers with high (24 kDa) molecular weights were identical for both grafting methods. Monolayers prepared from an ethanolic solution of poly(glycidyl ether)s equipped with sterically demanding disulfide-containing anchors revealed the lowest degrees of chain overlap. The ratio of the radius of gyration to the anchor distance (2 R g /l) of the latter coating was found to be lower than 1.4, indicating that the assembly was rather in the mushroom-like than in the brush regime. Polymer chains with thiol-containing anchors of different alkyl chain lengths (C 11 SH vs C 4 SH) formed assemblies with comparable degrees of chain overlap with 2 R g /l values above 1.4 and are thus in the brush regime. Molecular weights influenced the achievable degree of chain overlap on the surface. Coatings prepared with the medium molecular weight polymer (9 kDa) resulted in the highest chain packing density. Control of grafting density and thus chain overlap in different regimes (brush vs mushroom) on planar gold substrates are attainable for monolayer coatings with poly(GME-ran-EGE) by adjusting the polymer's molecular weight and anchor group as well as the conditions for the grafting-to procedure.

CRITERIA FOR CONSULTANT AND ADVISOR IN THE BRAZILIAN POSTGRADUATE SYSTEM.

PubMed

Petroianu, Andy

2015-01-01

To review the rules, resolutions and existing documents relating to consultant and advisor to better target the actions of those who exercise these roles. The following documents were consulted: Statute of CAPES, through Decree No. 7692 of March 2, 2012; Ordinance No. 47 of 17/10/1995; Opinion 977 1965 Newton Sucupira; Area Document of Medicine III; Interministerial Ordinance 251 of 2012, based on Decree No. 7642 of 2011 of the Ministry of Science and Technology; CAPES Regiment. The Brazilian Postgraduate system is divided in two different fields, according to its aspects: the "lato sensu" postgraduate, defined as all professional studies performed after the high school graduation; and the "stricto sensu" postgraduate that includes the master degree and the doctorate, both of them different from what is known as MSc or MS and PhD. The Brazilian doctorate is recognized as academic because its purposes include to improve the scientific and the teaching levels of university docents. The master degree has two different objectives one is to be academic and similar to the doctorate; the other is to upgrade professionals to a higher level than specialist or MBA and is denominated professional master degree. The master degrees and the doctorate are designated as courses and may be put together in a structure known as stricto sensu postgraduate program. The complexity of these courses and programs in all the areas of the superior human knowledge requires a large number of professional directly involved with this system and other professionals that attend them, called consultants and advisors. The consultants are counselors, and the advisors are assistants, both of them legally established with the incumbency to aid the postgraduate staff in all their duties. Nothing prevents a person from being a consultant on the situation and advisor on another, even in the same institution. Have knowledge about what being a consultant and advisor is required to exercise the function within the limits and dimension that the wingspan of the professional allows. Revisar as normas, resoluções e documentos vigentes relativos ao tema consultoria e assessoria para melhor orientar as atuações de quem exerce esses papéis. Foram consultados os seguintes documentos: Estatuto da CAPES, por meio do Decreto Nº 7.692, de 02 de março de 2012; Portaria nº 47 de 17/10/1995; Parecer 977 de 1965 de Newton Sucupira; Documento de Área da Medicina III; Portaria Interministerial 251 de 2012, com base no Decreto nº 7642 de 2011 do Ministério de Ciência e Tecnologia; e Regimento da CAPES. O gerenciamento dos programas de pós-graduação stricto sensu requer estrutura multiprofissional diversificada em todos os seus níveis, constituída por corpo próprio da instituição e por componentes agregados, incluindo os consultores e assessores. O consultor é pessoa independente, sem vínculo com quem o convida e, nesse sentido, espera-se dele isenção na execução das tarefas solicitadas, nas quais se pressupõe domínio cultural, científico e humanístico. No Documento de Área da Medicina III, a consultoria é valorizada como atributo importante do Corpo Docente e está mencionada na Proposta dos Programas de Pós-graduação em seu item 2.1. Por outro lado, o assessor está vinculado ao solicitante em relação de dependência funcional. Dentro de sua área do conhecimento, o assessor é considerado adjunto do solicitante e pode substituí-lo ou representá-lo. No Documento de Área da Medicina III, o desempenho de assessoria pelo Corpo Docente está mencionado na Proposta dos Programas de Pós-graduação em seu item 5.2. Ter conhecimento sobre o que significa ser consultor e assessor é necessário para exercer a função dentro dos limites que lhe compete e na dimensão que a envergadura do profissional permite. Nada impede que uma pessoa seja consultora em situação e assessora em outra, até na mesma instituição. Ter conhecimento sobre o que significa ser consultor e assessor é necessário para poder exercer a função dentro dos limites que lhe compete e na dimensão que a envergadura do profissional permite.

Telescópio de patrulhamento solar em 12 GHz

NASA Astrophysics Data System (ADS)

Utsumi, F.; Costa, J. E. R.

2003-08-01

O telescópio de patrulhamento solar é um instrumento dedicado à observação de explosões solares com início de suas operações em janeiro de 2002, trabalhando próximo ao pico de emissão do espectro girossincrotrônico (12 GHz). Trata-se de um arranjo de três antenas concebido para a detecção de explosões e determinação em tempo real da localização da região emissora. Porém, desde sua implementação em uma montagem equatorial movimentada por um sistema de rotação constante (15 graus/hora) o rastreio apresentou pequenas variações de velocidade e folgas nas caixas de engrenagens. Assim, tornou-se necessária a construção de um sistema de correção automática do apontamento que era de fundamental importância para os objetivos do projeto. No segundo semestre de 2002 empreendemos uma série de tarefas com o objetivo de automatizar completamente o rastreio, a calibração, a aquisição de dados, controle de ganhos, offsets e transferência dos dados pela internet através de um projeto custeado pela FAPESP. O rastreio automático é realizado através de um inversor que controla a freqüência da rede de alimentação do motor de rastreio podendo fazer micro-correções na direção leste-oeste conforme os radiômetros desta direção detectem uma variação relativa do sinal. Foi adicionado também um motor na direção da declinação para correção automática da variação da direção norte-sul. Após a implementação deste sistema a precisão do rastreio melhorou para um desvio máximo de 30 segundos de arco, o que está muito bom para este projeto. O Telescópio se encontra em funcionamento automático desde março de 2003 e já conta com várias explosões observadas após a conclusão desta fase de automação. Estamos apresentando as explosões mais intensas do período e com as suas respectivas posições no disco solar.

A cosmologia no ensino da geografia

NASA Astrophysics Data System (ADS)

Santos, S. C.; Chiaradia, A. P. M.

2003-08-01

O principal objetivo deste trabalho é auxiliar o professor de Geografia em sala de aula no ensino de tópicos relacionados com a Cosmologia. A idéia deste trabalho surgiu quando foi constatado que o professor de Geografia tem dificuldades de ensinar este tópico. Esta constatação foi feita por uma das autoras ao lecionar este tópico no ensino fundamental e em discussões com outros professores de Geografia. Da mesma maneira que ocorria desde os tempos mais antigos, os alunos têm muito interesse em conhecer os fenômenos que ocorrem no Cosmo, porém os livros didáticos de Geografia utilizados em sala de aula não são ricos em informações sobre este assunto. Assim, o professor de Geografia tem poucas informações para discutir este assunto em sala de aula e não dá a devida importância para este tópico. Então, foi desenvolvido um material de apoio para professores de Geografia sobre a origem do Universo, sua evolução e seu possível futuro evolutivo segundo as mais recentes teorias, com base em perguntas feitas pelos alunos de ensino fundamental e as informações trazidas nos livros didáticos Não cabe a este material inovar e tão pouco trazer uma metodologia de ensino de Cosmologia. Neste material o professor de Geografia pode encontrará um banco de informações, que constitui no estabelecimento de conceitos, teorias e hipóteses, sobre a Cosmologia, em linguagem simples e de fácil entendimento. Para desenvolvê-lo, foram feitas pesquisas não exaustivas em livros e revistas científicas, compilação e discussão em forma cronológica das teorias aceitas sobre modelos cosmológicos. Portanto, este material será apresentado neste trabalho.

Knowledge, attitude and practice of the smear test and its relation with female age.

PubMed

Silveira, Nara Sibério Pinho; Vasconcelos, Camila Teixeira Moreira; Nicolau, Ana Izabel Oliveira; Oriá, Mônica Oliveira Batista; Pinheiro, Patricia Neyva da Costa; Pinheiro, Ana Karina Bezerra

2016-06-14

to verify the association among the knowledge attitude and practice of women in relation to the smear test and the age range. a cross-sectional research was undertaken, associated with the knowledge, attitude and practice survey at a Primary Health Care service. The sample consisted of 775 women, distributed in three age ranges: adolescent, young and elderly. although high rates of inappropriate knowledge were found in all age ranges, it was significantly higher among the adolescents (p=0.000). A similar trend was found in the attitude component, with percentages of inappropriateness in adolescence that drop as age advances (p=0.000). Nevertheless, no statistical difference among the groups was found in terms of practice (p=0.852). the study demonstrated a relation between the age range and knowledge, attitude and practice of the smear test. verificar a associação entre o conhecimento, atitude e prática de mulheres em relação ao exame colpocitológico e a faixa etária. trata-se de pesquisa de corte transversal associada ao inquérito conhecimento, atitude e prática, em uma Unidade de Atenção Primária à Saúde. A amostra foi composta por 775 mulheres, distribuídas em três faixas etárias: adolescentes, jovens e idosas. embora o conhecimento inadequado tenha tido altas taxas em todas as faixas etárias, foi significativamente superior entre as adolescentes (p=0,000). Tendência semelhante no componente atitude por apresentar percentuais de inadequabilidade na adolescência e decair com o avançar da idade (p=0,000). Todavia, não houve diferença estatística entre os grupos quanto à prática (p=0,852). o estudo demonstrou relação entre a faixa etária e o conhecimento, a atitude e a prática do exame colpocitológico. verificar la asociación entre el conocimiento, la actitud y práctica de mujeres con relación a la prueba colpocitológica y el rango de edad. se trata de investigación trasversal asociada a la encuesta conocimiento, actitud y práctica, en una Unidad de Atención Primaria de Salud. La muestra abarcó a 775 mujeres, distribuidas en tres rangos de edad: adolescentes, jóvenes y ancianas. aunque el conocimiento inadecuado tenga mostrada altas tasas en todos los rangos de edad, fue significativamente superior entre las adolescentes (p=0,000). Tendencia semejante en el componente actitud, debido a porcentajes de inadecuación en la adolescencia, disminuyendo con el avance de la edad (p=0,000). Sin embargo, no fue encontrada diferencia estadística entre los grupos respecto a la práctica (p=0,852). el estudio demostró relación entre el rango de edad y el conocimiento, la actitud y la práctica de la prueba colpocitológica.

[Regulating the internet: a comparative analysis of Brazil, Chile, Spain, the US, and France].

PubMed

Segurado, Rosemary; Lima, Carolina Silva Mandú de; Ameni, Cauê S

2015-12-01

Global governance is of key concern in the current debate over the workings of the world's computer network, and Brazil has played a notable role in this process, especially after approval of the Marco Civil da Internet (law 12.965, april 23, 2014), which defines Brazil's regulatory framework for the internet. Dubbed the internet bill of rights, this law sets out the principles, guarantees, rights, and duties of internet users and providers in Brazil. Based on the fundamental categories of net neutrality, internet users' right to privacy, and copyright discussions from the perspective of intellectual property, the article offers a comparative analysis of regulations in five countries: Brazil, Chile, Spain, the US, and France.

Cross-Cultural adaptation of the General Functioning Scale of the Family.

PubMed

Pires, Thiago; Assis, Simone Gonçalves de; Avanci, Joviana Quintes; Pesce, Renata Pires

2016-06-27

To describe the process of cross-cultural adaptation of the General Functioning Scale of the Family, a subscale of the McMaster Family Assessment Device, for the Brazilian population. The General Functioning Scale of the Family was translated into Portuguese and administered to 500 guardians of children in the second grade of elementary school in public schools of Sao Gonçalo, Rio de Janeiro, Southeastern Brazil. The types of equivalences investigated were: conceptual and of items, semantic, operational, and measurement. The study involved discussions with experts, translations and back-translations of the instrument, and psychometric assessment. Reliability and validity studies were carried out by internal consistency testing (Cronbach's alpha), Guttman split-half correlation model, Pearson correlation coefficient, and confirmatory factor analysis. Associations between General Functioning of the Family and variables theoretically associated with the theme (father's or mother's drunkenness and violence between parents) were estimated by odds ratio. Semantic equivalence was between 90.0% and 100%. Cronbach's alpha ranged from 0.79 to 0.81, indicating good internal consistency of the instrument. Pearson correlation coefficient ranged between 0.303 and 0.549. Statistical association was found between the general functioning of the family score and the theoretically related variables, as well as good fit quality of the confirmatory analysis model. The results indicate the feasibility of administering the instrument to the Brazilian population, as it is easy to understand and a good measurement of the construct of interest. Descrever o processo de adaptação transcultural da escala de Funcionamento Geral da Família, subescala da McMaster Family Assessment Device, para a população brasileira. A escala de Funcionamento Geral da Família, original no idioma inglês, foi traduzida para o português e aplicada a 500 responsáveis de crianças do segundo ano do ensino fundamental de escolas públicas do município de São Gonçalo, Rio de Janeiro. Os tipos de equivalências investigados foram: conceitual e de itens, semântica, operacional, e mensuração. O estudo envolveu discussão com especialistas, traduções e retraduções do instrumento e avaliação psicométrica. Foi realizado estudo de confiabilidade e validade, por testagem da consistência interna (alpha de Cronbach), da correlação pelo método de split-half de Guttman e do coeficiente de correlação de Pearson, e por análise fatorial confirmatória. Associações entre Funcionamento Geral da Família e variáveis teoricamente associadas ao tema (embriaguez do pai ou da mãe e violência entre os pais) foram analisadas por estimação de razão de chance. A equivalência semântica encontrada foi entre 90,0% e 100%. O alfa de Cronbach variou de 0,79 a 0,81, indicando boa consistência interna do instrumento. O coeficiente de correlação de Pearson oscilou entre 0,303 e 0,549. Encontrou-se associação estatística entre o escore de funcionamento geral da família e as variáveis teoricamente relacionadas e constatou-se boa qualidade dos ajustes do modelo de análise confirmatória. Os resultados obtidos indicam a aplicabilidade do instrumento na população brasileira, que se mostra de fácil compreensão e boa aferição do constructo de interesse.

Patient Safety Incidents and Nursing Workload.

PubMed

Carlesi, Katya Cuadros; Padilha, Kátia Grillo; Toffoletto, Maria Cecília; Henriquez-Roldán, Carlos; Juan, Monica Andrea Canales

2017-04-06

to identify the relationship between the workload of the nursing team and the occurrence of patient safety incidents linked to nursing care in a public hospital in Chile. quantitative, analytical, cross-sectional research through review of medical records. The estimation of workload in Intensive Care Units (ICUs) was performed using the Therapeutic Interventions Scoring System (TISS-28) and for the other services, we used the nurse/patient and nursing assistant/patient ratios. Descriptive univariate and multivariate analysis were performed. For the multivariate analysis we used principal component analysis and Pearson correlation. 879 post-discharge clinical records and the workload of 85 nurses and 157 nursing assistants were analyzed. The overall incident rate was 71.1%. It was found a high positive correlation between variables workload (r = 0.9611 to r = 0.9919) and rate of falls (r = 0.8770). The medication error rates, mechanical containment incidents and self-removal of invasive devices were not correlated with the workload. the workload was high in all units except the intermediate care unit. Only the rate of falls was associated with the workload. identificar a relação entre a carga de trabalho da equipe de enfermagem e a ocorrência de incidentes de segurança dos pacientes ligados aos cuidados de enfermagem de um hospital público no Chile. pesquisa transversal analítica quantitativa através de revisão de prontuários médicos. A estimativa da carga de trabalho em Unidade de Terapia Intensiva (UTI) foi realizada utilizando o Índice de Intervenções Terapêuticas-TISS-28 e para os outros serviços, foram utilizados os cocientes enfermeira/paciente e auxiliar de enfermagem/ paciente. Foram feitas análises univariada descritiva e multivariada. Para a análise multivariada utilizou-se análise de componentes principais e correlação de Pearson. foram analisados 879 prontuáriosclínicos de pós-alta e a carga de trabalho de 85 enfermeiros e 157 auxiliares de enfermagem. A taxa global de incidentes foi de 71,1%. Foi encontrada uma alta correlação positiva entre as variáveis de carga de trabalho (r = 0,9611 para r = 0,9919) e a taxa de quedas (r = 0,8770). As taxas de erro de medicação, incidentes de contenção mecânica e auto remoção de dispositivos invasivos não foram correlacionadas com a carga de trabalho. a carga de trabalho foi elevada em todas as unidades, exceto na unidade de cuidados intermédios. Apenas a taxa de quedas foi associada com a carga de trabalho. identificar la relación entre la carga laboral del equipo de enfermería y la ocurrencia de incidentes de seguridad del paciente relacionados con los cuidados de enfermería en un hospital público de Chile. investigación cuantitativa, analítica, transversal, realizada por revisión de fichas clínicas. La estimación de carga laboral en las Unidades de Cuidados Intensivos (UCI) se realizó utilizando el Índice de Intervenciones Terapéuticas (TISS-28) y, para el resto de los servicios, por la relación enfermera/paciente y auxiliar/paciente. Se realizó análisis descriptivo univariado y multivariado. Para el análisis multivariado se utilizó análisis de componentes principales y el test de correlación de Pearson. se revisaron 879 fichas clínicas posteriores al alta y la carga laboral de 85 enfermeras y 157 auxiliares de enfermería. La tasa global de incidentes fue 71,1%. Se encontró correlación positiva alta entre las variables de carga laboral (r = 0,9611 a r = 0,9919) y tasa de caídas (r = 0,8770). Las tasas de error de medicación, incidente por contención mecánica y auto retiro de invasivos no se correlacionaron con la carga laboral. la carga laboral fue elevada en todas las unidades a excepción de la unidad de cuidados intermedios. Sólo la tasa de caídas se asoció a la carga laboral.

Fotometria superficial BVRI de 18 galáxias fracas

NASA Astrophysics Data System (ADS)

Saraiva, M. F. O.; Silva, P. R.

2003-08-01

Conhecer as propriedades de galáxias a diferentes redshifts é uma questão fundamental para entender o problema da formação e evolução das galáxias, e desde a década passada tem se intensificado fortemente o estudo de galáxias muito distantes. No entanto parece haver um interesse menor em galáxias a distâncias intermediárias, que aparecem como objetos de fundo em imagens de objetos próximos, e que são igualmente importantes. Examinando imagens BVRI de longa exposição, ótimo sinal/ruído, grande campo (46'x46'), das vizinhanças de NGC 7479, detectamos 18 galáxias fracas (18 < B < 21) nessas imagens. Neste trabalho, apresentamos a fotometria superficial desses objetos. Determinamos coordenadas equatoriais, magnitudes e cores integradas, perfis de brilho e de cor, e parâmetros isofotais calculados por ajuste de ellipses, dentro do limite permitido pela baixa resolução espacial dos dados (1,35 segarc/pixel). Nosso objetivo é procurar correlações entre as propriedades das galáxias e, tentativamente, comparar esses dados com aqueles de galáxias de redshift conhecido, disponíveis na literatura, para estimar suas distâncias (a partir da relação cor x redshift) e suas morfologias. Uma análise preliminar nesse sentido mostrou que as cores aparentes B-V, V-R e V-I dos objetos da nossa amostra, a menos de duas exceções, ocupam regiões bem definidas nos diagramas cor-cor, e não apresentam diferenças notáveis em relação às cores típicas de galáxias próximas.

Fatigue History and in-situ Loading Studies of the overload Effect Using High Resolution X-ray Strain Profiling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croft,M.; Jisrawi, N.; Zhong, Z.

High-energy synchrotron X-ray diffraction experiments are used to perform local crack plane strain profiling of 4140 steel compact tension specimens fatigued at constant amplitude, subjected to a single overload cycle, then fatigued some more at constant amplitude. X-ray strain profiling results on a series of samples employing in-situ load cycling are correlated with the crack growth rate (da/dN) providing insight into the da/dN retardation known as the 'overload effect'. Immediately after the overload, the strain under maximum load is greatly reduced but the range of strain, between zero and maximum load, remains unchanged compared to the pre-overload values. At themore » point of maximum retardation, it is the strain range that is greatly reduced while the maximum-load strain has begun to recover to the pre-overload value. For a sample that has recovered to approximately half of the original da/dN value following the overload, the strain at maximum load is fully recovered while the strain range, though partially recovered, is still substantially reduced. The dominance of the strain range in the overload effect is clearly indicated. Subject to some assumptions, strong quantitative support for a crack growth rate driving force of the suggested form [(K{sub max}){sup -p}({Delta}K){sup p}]{sup {gamma}} is found. A dramatic nonlinear load dependence in the spatial distribution of the strain at maximum retardation is also demonstrated: at low load the response is dominantly at the overload position; whereas at high loads it is dominantly at the crack tip position. This transfer of load response away from the crack tip to the overload position appears fundamental to the overload effect for high R-ratio fatigue as studied here.« less

Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.

PubMed

Cheng, Behling; Al-Shammari, Fatema H; Ghader, Isra'a A; Sequeira, Fatima; Thakkar, Jitendra; Mathew, Thazhumpal C

2017-07-01

Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRβ were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

A strategy to minimize the energy offset in carrier injection from excited dyes to inorganic semiconductors for efficient dye-sensitized solar energy conversion.

PubMed

Fujisawa, Jun-Ichi; Osawa, Ayumi; Hanaya, Minoru

2016-08-10

Photoinduced carrier injection from dyes to inorganic semiconductors is a crucial process in various dye-sensitized solar energy conversions such as photovoltaics and photocatalysis. It has been reported that an energy offset larger than 0.2-0.3 eV (threshold value) is required for efficient electron injection from excited dyes to metal-oxide semiconductors such as titanium dioxide (TiO2). Because the energy offset directly causes loss in the potential of injected electrons, it is a crucial issue to minimize the energy offset for efficient solar energy conversions. However, a fundamental understanding of the energy offset, especially the threshold value, has not been obtained yet. In this paper, we report the origin of the threshold value of the energy offset, solving the long-standing questions of why such a large energy offset is necessary for the electron injection and which factors govern the threshold value, and suggest a strategy to minimize the threshold value. The threshold value is determined by the sum of two reorganization energies in one-electron reduction of semiconductors and typically-used donor-acceptor (D-A) dyes. In fact, the estimated values (0.21-0.31 eV) for several D-A dyes are in good agreement with the threshold value, supporting our conclusion. In addition, our results reveal that the threshold value is possible to be reduced by enlarging the π-conjugated system of the acceptor moiety in dyes and enhancing its structural rigidity. Furthermore, we extend the analysis to hole injection from excited dyes to semiconductors. In this case, the threshold value is given by the sum of two reorganization energies in one-electron oxidation of semiconductors and D-A dyes.

White matter microstructure in a genetically defined group at increased risk of autism symptoms, and a comparison with idiopathic autism: an exploratory study.

PubMed

Goddard, Marcia N; van Rijn, Sophie; Rombouts, Serge A R B; Swaab, Hanna

2016-12-01

Klinefelter syndrome (47,XXY) is associated with physical, behavioral, and cognitive consequences. Deviations in brain structure and function have been reported, but structural characteristics of white matter have barely been assessed. This exploratory diffusion tensor imaging study assessed white matter microstructure in boys with 47,XXY compared with non-clinical, male controls. Additionally, both similarities and differences between 47,XXY and autism spectrum disorders (ASD) have been reported in cognition, behavior and neural architecture. To further investigate these brain-behavior pathways, white matter microstructure in boys with 47,XXY was compared to that of boys with ASD. Fractional anisotropy (FA), radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) were assessed in 47,XXY (n = 9), ASD (n = 18), and controls (n = 14), using tract-based spatial statistics. Compared with controls, boys with 47,XXY have reduced FA, coupled with reduced Da, in the corpus callosum. Boys with 47,XXY also have reduced Dr. in the left anterior corona radiata and sagittal striatum compared with controls. Compared with boys with ASD, boys with 47,XXY show reduced Da in the right inferior fronto-occipital fasciculus. Although this study is preliminary considering the small sample size, reduced white matter integrity in the corpus callosum may be a contributing factor in the cognitive and behavioral problems associated with 47,XXY. In addition, the differences in white matter microstructure between 47,XXY and ASD may be important for our understanding of the mechanisms that are fundamental to behavioral outcome in social dysfunction, and may be targeted through intervention.

Validation of a virtual reality-based robotic surgical skills curriculum.

PubMed

Connolly, Michael; Seligman, Johnathan; Kastenmeier, Andrew; Goldblatt, Matthew; Gould, Jon C

2014-05-01

The clinical application of robotic-assisted surgery (RAS) is rapidly increasing. The da Vinci Surgical System™ is currently the only commercially available RAS system. The skills necessary to perform robotic surgery are unique from those required for open and laparoscopic surgery. A validated laparoscopic surgical skills curriculum (fundamentals of laparoscopic surgery or FLS™) has transformed the way surgeons acquire laparoscopic skills. There is a need for a similar skills training and assessment tool specific for robotic surgery. Based on previously published data and expert opinion, we developed a robotic skills curriculum. We sought to evaluate this curriculum for evidence of construct validity (ability to discriminate between users of different skill levels). Four experienced surgeons (>20 RAS) and 20 novice surgeons (first-year medical students with no surgical or RAS experience) were evaluated. The curriculum comprised five tasks utilizing the da Vinci™ Skills Simulator (Pick and Place, Camera Targeting 2, Peg Board 2, Matchboard 2, and Suture Sponge 3). After an orientation to the robot and a period of acclimation in the simulator, all subjects completed three consecutive repetitions of each task. Computer-derived performance metrics included time, economy of motion, master work space, instrument collisions, excessive force, distance of instruments out of view, drops, missed targets, and overall scores (a composite of all metrics). Experienced surgeons significantly outperformed novice surgeons in most metrics. Statistically significant differences were detected for each task in regards to mean overall scores and mean time (seconds) to completion. The curriculum we propose is a valid method of assessing and distinguishing robotic surgical skill levels on the da Vinci Si™ Surgical System. Further study is needed to establish proficiency levels and to demonstrate that training on the simulator with the proposed curriculum leads to improved robotic surgical performance in the operating room.

Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) explored as a potential electrochemical sensor for dopamine: surfactants significantly influence sensor capabilities.

PubMed

Khan, Aamar F; Brownson, Dale A C; Foster, Christopher W; Smith, Graham C; Banks, Craig E

2017-05-21

Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) nanosheets are explored as a potential electrochemical sensing platform and evaluated towards the electroanalytical sensing of dopamine (DA) in the presence of the common interferents, ascorbic acid (AA) and uric acid (UA). Surfactant exfoliated 2D-hBN nanosheets (2-4 layers) fabricated using sodium cholate in aqueous media are electrically wired via a drop-casting modification process onto disposable screen-printed graphite electrodes (SPEs). We critically evaluate the performance of these 2D-hBN modified SPEs and demonstrate the effect of 'mass coverage' towards the detection of DA, AA and UA. Previous studies utilising surfactant-free (pristine) 2D-hBN modified SPEs have shown a beneficial effect towards the detection of DA, AA and UA when compared to the underlying/unmodified graphite-based electrode. We show that the fabrication route utilised to prepare 2D-hBN is a vital experimental consideration, such that the beneficial effect previously reported is considerably reduced when surfactant exfoliated 2D-hBN is utilised. We demonstrate for the first time, through implementation of control experiments in the form of surfactant modified graphite electrodes, that sodium cholate is a major contributing factor to the aforementioned detrimental behaviour. The significance here is not in the material per se, but the fundamental knowledge of the surfactant and surface coverage changing the electrochemical properties of the material under investigation. Given the wide variety of ionic and non-ionic surfactants that are utilised in the manufacture of novel 2D materials, the control experiments reported herein need to be performed in order to de-convolute the electrochemical response and effectively evaluate the 'underlying surface/surfactant/2D materials' electrocatalytic contribution.

A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes.

PubMed

Ogawa, Akira; Streit, Adrian; Antebi, Adam; Sommer, Ralf J

2009-01-13

Under harsh environmental conditions, Caenorhabditis elegans larvae undergo arrest and form dauer larvae that can attach to other animals to facilitate dispersal. It has been argued that this phenomenon, called phoresy, represents an intermediate step toward parasitism. Indeed, parasitic nematodes invade their hosts as infective larvae, a stage that shows striking morphological similarities to dauer larvae. Although the molecular regulation of dauer entry in C. elegans involves insulin and TGF-beta signaling, studies of TGF-beta orthologs in parasitic nematodes didn't provide evidence for a common origin of dauer and infective larvae. To identify conserved regulators between Caenorhabditis and parasitic nematodes, we used an evolutionary approach involving Pristionchus pacificus as an intermediate. We show by mutational and pharmacological analysis that Pristionchus and Caenorhabditis share the dafachronic acid-DAF-12 system as the core endocrine module for dauer formation. One dafachronic acid, Delta7-DA, has a conserved role in the mammalian parasite Strongyloides papillosus by controlling entry into the infective stage. Application of Delta7-DA blocks formation of infective larvae and results in free-living animals. Conservation of this small molecule ligand represents a fundamental link between dauer and infective larvae and might provide a general strategy for nematode parasitism.

Latest research results on the effects of nanomaterials on humans and the environment: DaNa - Knowledge Base Nanomaterials

NASA Astrophysics Data System (ADS)

Marquardt, C.; Kühnel, D.; Richter, V.; Krug, H. F.; Mathes, B.; Steinbach, C.; Nau, K.

2013-04-01

Nanotechnology is considered one of the key technologies of the 21st century. The success of this fascinating technology is based on its versatility. It will bring about fundamental changes of basic research as well as of many sectors of industry and also of daily life from electronics to the health care system. However, consumers often miss reliable and understandable information on nanomaterials and all aspects of this versatile technology. A huge body of data on the potential hazards of nanoobjects towards human and environmental health already exists, but is either not easily accessible for a broad audience or presented unprocessable for nonexperts. But risk communication is an essential and thus integral component of risk management. For that purpose, the DaNa-Project aims at filling this gap by collecting and evaluating scientific results in an interdisciplinary approach with scientists from different research areas, such as human and environmental toxicology, biology, physics, chemistry, and sociology. Research findings from the field of human and environmental nanotoxicology are being prepared and presented together with material properties and possible applications for interested laymen and stakeholders. For the evaluation of literature a "Literature Criteria Checklist" has been developed as well as a Standard Operation Procedure template (SOP) based on careful scientific practice.

Estimating KC-137 Aircraft Ownership Costs in the Brazilian Air Force

DTIC Science & Technology

1997-06-01

Cycle Costing A-1 M manpower m meter Maint. Maintenance Mainten. Maintenance O&S Operation and Support OPAC Online Public Access Catalog PAMAGL Parque ...1.2 e 1.3. ))as informag6es quanto a pagarnento dar~o urn pouco de trabaiho, mas creio que podern ser conseguidas na tesouraria do Parque . N~o basta...pela Base na manutengo das aeronaves (e que n~o sejam fornecidos pelo Parque ), tais como gaxetas, componentes eletr6nicos, brocas, produtos qufmicos, etc

Componente de la envoltura en la discontinuidad de Balmer de estrellas Be

NASA Astrophysics Data System (ADS)

Rohrmann, R. D.; Cidale, L.

En modelos de atmósferas en expansión de estrellas Be se estudia la contribución al salto de Balmer de una envoltura circunestelar. Se busca relacionar el salto de Balmer fotosférico y el salto de Balmer originado en la envoltura con los distintos parámetros de la atmósfera (dimensión de la cromosfera, ley de expansión, tasa de pérdida de masa, etc.).

Report on 2005 Defense Base Closure and Realignment Implementation

DTIC Science & Technology

2007-04-01

Marcos 559 ARNG RC Seguin 560 ARNG RC Snyder 561 ARNG RC Taylor 562 ARNG RC Terrell 563 ARNG RC Texarkana 564 ARNG RC Tyler 565 Benavidez USARC, El...realignment actions: Sep 1 2011 563 ARNG RC Texarkana , TX Commission recommendation(s) affected by this installation: Number Title 44 Reserve Component...AL421382002700 State: Alabama Sites Sites RC Total 51 38 Phase Beg. End <=2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

Astronomia cultural e meio ambiente segundo uma abordagem holística

NASA Astrophysics Data System (ADS)

Jafelice, L. C.

2003-08-01

Neste trabalho ampliamos a discussão da abordagem holística para o ensino de astronomia que temos desenvolvido nos últimos anos, analisamos novos resultados e apresentamos exemplos práticos para interessados em experimentá-la. A constatação básica a orientar este enfoque é que cursos introdutórios em astronomia costumam ser excessiva e prematuramente técnicos, além de assumirem uma visão tradicional, muito estreita, do que seja educação científica, herdada da era cartesiana e positivista da ciência. Fundamentamos porque é importante que elementos de astronomia cultural ofereçam o mote e constituam o eixo norteador daqueles cursos e porque é urgente revermos a visão que temos da relação entre astronomia e meio ambiente. Um ponto central nesta abordagem é explorar formas de reativar e atualizar uma relação orgânica com o meio e excitar a consciência de nossa inevitável e profunda interdependência com ele em nível cósmico. Neste trabalho exemplificamos a possibilidade de concretização desta proposta em três diferentes situações: disciplinas de cursos de licenciatura em geografia e em física; escolas de nível fundamental; e, neste caso ainda a ser implementada, comunidades carentes. Estes casos envolvem públicos e espaços diferenciados para educação formal e não-formal. Dos casos já implementados, destacamos os resultados alcançados pelos alunos: enriquecimento cultural, aprendizagem significativa de conteúdos astronômicos tradicionais; mudanças de comportamento, incorporando contato diário com o céu; e freqüentes vivências de sentimentos empáticos que redirecionam a relação com a natureza e a consciência ecológica global. Além disto, para interessados em aplicar esta proposta, também socializamos procedimentos e cuidados para a implementação de ações alternativas consonantes com a mesma. (PPGECNM/UFRN; PRONEX/FINEP; NUPA/USP; Temáticos/FAPESP)

Cocaine sensitization increases subthreshold activity in dopamine neurons from the ventral tegmental area.

PubMed

Arencibia-Albite, Francisco; Vázquez-Torres, Rafael; Jiménez-Rivera, Carlos A

2017-02-01

The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed I h We recently demonstrated that I h and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize I h and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at -70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. I h attenuation is unlikely to explain such observations, since at -70 mV, no statistical differences exist in I h or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase. This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane capacitance (C m ) and rate at any time point of the synaptic waveform. The use of such methodology shows that cocaine sensitization reduces C m and increases the speed of synaptic signaling. Paradoxically, although synaptic potentials show a faster decay under cocaine their temporal summation is substantially elevated. Copyright © 2017 the American Physiological Society.

Epidemiological surveillance of tegumentary leishmaniasis: local territorial analysis.

PubMed

Soares, Valdenir Bandeira; Almeida, Andréa Sobral de; Sabroza, Paulo Chagastelles; Vargas, Waldemir Paixão

2017-06-26

To propose a new operational unit in the locality scale capable of subsidizing the construction of an information system to control the transmission of tegumentary leishmaniasis at this scale, in a region of high endemicity of the Atlantic Forest. We examined the adequacy of data and instruments in an area of high endemicity in the Atlantic Forest located in the South of the State of Rio de Janeiro from 1990 to 2012. The study proposed an operational unit called Local Surveillance Unit to make all used databases compatible by adjusting census sectors. This enabled the overlap and comparison of information in different periods. The spreading process of the transmission of tegumentary leishmaniasis in the Baía da Ilha Grande region does not depend on great population movements, and can occur in areas with population growth or decrease. The data information system allowed the adequate identification and characterization of the place of residence. We identified relevant characteristics of the place of transmission, such as self-limited in time and not associated with recent deforestation. The results also highlight the lack of synchronicity in the case production in territorial units involved in the endemic-epidemic process, noting that this process is in constant motion. The transmission process seems more connected to the presence and movement of rodents that move continuously in the region than to the local density of vectors or the permanence of infected dogs at home. New control strategies targeted at the foci of transmission must be considered. The construction of a new operational unit, called Local Surveillance Unit, was instrumental in the endemic-epidemic process analysis. Propor uma nova unidade operacional na escala de localidade capaz de subsidiar a construção de um sistema de informação orientado para o controle da transmissão da leishmaniose tegumentar nesse nível. Uma região de alta endemicidade da Mata Atlântica no sul do estado do Rio de Janeiro de 1990 a 2012 foi selecionada para analisar a adequação dos dados e instrumentos. Uma unidade operacional denominada Unidade de Vigilância Local foi proposta para compatibilizar todos os bancos de dados utilizados por meio de ajustes dos setores censitários. Isso possibilitou a sobreposição das informações e a sua comparação em diferentes períodos. O processo de deslocamento da transmissão da leishmaniose tegumentar na região da Baía da Ilha Grande não dependeu de movimentos populacionais importantes, podendo ocorrer tanto em áreas com crescimento como em áreas com decremento populacional. Os dados do sistema de informação permitiram a identificação e caracterização adequada do local de residência. Identificaram-se características relevantes do lugar de transmissão, como autolimitados no tempo e não associados a desmatamentos recentes. Os resultados evidenciam também a falta de sincronicidade na produção de casos nas unidades territoriais envolvidas no processo endêmico-epidêmico, mostrando que esse processo está em constante movimento. O processo de transmissão parece estar mais ligado à presença e circulação de roedores que se desloquem continuadamente na região do que da densidade local de vetores ou da permanência de cães infectados no domicílio. Novas estratégias de controle orientadas para os focos de transmissão devem ser consideradas. A construção de uma nova unidade operacional, denominada Unidade de Vigilância Local, foi fundamental na análise do processo endêmico-epidêmico.

Teaching of Astronomy: Scenarios of Teaching Practice in Elementary Schools. (Spanish Title: Enseñanza de la Astronomía: Semblanzas de la Práctica Docente en Educación Primaria.) Ensino de Astronomia: Cenários da Prática Docente no Ensino Fundamental

NASA Astrophysics Data System (ADS)

Marchi Gonzatti, Sônia Elisa; Spessatto De Maman, Andréia; Fernandes Borragini, Eliana; Kerber, Júlia Cristina; Haetinger, Werner

2013-12-01

The present work presents the main results of a research carried out within the Astronomy Education field with Elementary School teachers from two regions of Rio Grande do Sul. The study aimed to show the regional panorama of teaching Astronomy compared to the national panorama already discussed in several studies in the area. It was divided into three main issues: identifying the main topics of Astronomy developed in class, verifying which were the methodological strategies used, and which were the difficulties teachers faced when developing their practice. Regarding the contents, it was found a wide range of covered topics although Earth motion and astronomical phenomena were cited by most participants. Concerning the strategies used in class, two-dimensional resources such as movies, texts, maps and web searching were mainly used. The most relevant difficulties were the lack of specific education related to Astronomy contents and abstraction level, which complicated the understanding for both students and teachers. In general, the indicators met the results already found in other studies that investigated Astronomy teaching practice, in which the teacher's original education deficiency - or even the lack of it - hampers the proper development of Astronomy contents in class. En este trabajo se presentan los principales resultados de una investigación hecha en el campo de la Educación en Astronomía, con profesores de la Enseñanza Fundamental de dos regiones de Rio Grande do Sul. El presente estudio tuvo como objetivo caracterizar el panorama regional de la enseñanza de Astronomía, estableciendo una comparación con el panorama nacional ya presentado en trabajos de referencia en el área. Ese estudio abordó tres cuestiones: identificar los principales temas de astronomía trabajados, las estrategias metodológicas y cuáles fueron las dificultades sufridas por los profesores al presentar su práctica. Con relación a los contenidos, se encontró una atomización de los asuntos, aunque temas como movimientos de la Tierra y fenómenos astronómicos hayan sido citados por la mayoría de los participantes. En cuanto a las estrategias, se verifico que se emplean principalmente clases con el apoyo de recursos bidimensionales, como películas, textos, mapas y búsqueda en internet. Las principales dificultades fueron la falta de formación específica con respecto a los contenidos de Astronomía, y el nivel de abstracción exigido por los contenidos. De modo general, esos indicadores convergen para los resultados ya encontrados en otros estudios, en el que las deficiencias de la formación inicial de los profesores, o incluso su ausencia, dificulta el adecuado abordaje de la Astronomía en las clases. Neste trabalho são apresentados os principais resultados de uma investigação realizada no campo da Educação em Astronomia, com professores do ensino fundamental de duas regiões do Rio Grande do Sul. O objetivo do estudo foi caracterizar o cenário regional do ensino de Astronomia, estabelecendo um comparativo com o cenário nacional. Esse estudo abordou três questões: identificar os principais temas de astronomia trabalhados em sala de aula, as estratégias metodológicas e quais as dificuldades apresentadas pelos professores ao desenvolver sua prática. Quanto aos conteúdos, encontrouse uma pulverização dos assuntos abordados, embora temas como movimentos da Terra e fenômenos astronômicos tenham sido citados pela maioria dos participantes. Sobre estratégias, são utilizadas principalmente aulas com apoio de recursos bidimensionais, como filmes, textos, mapas e pesquisa na internet. As principais dificuldades foram: falta de formação específica em relação a conteúdos de Astronomia; nível de abstração dos conteúdos, que dificultam sua compreensão, tanto pelos alunos quanto pelos próprios professores. De maneira geral, esses indicadores convergem para resultados já encontrados em outros estudos que investigam a prática docente em Astronomia, em que as deficiências da formação inicial dos professores, ou mesmo a falta dela, dificulta a adequada abordagem da Astronomia em sala de aula.

Resonant Acoustic Measurement of Vapor Phase Transport Phenomenon

NASA Astrophysics Data System (ADS)

Schuhmann, R. J.; Garrett, S. L.; Matson, J. V.

2002-12-01

A major impediment to accurate non steady-state diffusion measurements is the ability to accurately measure and track a rapidly changing gas concentration without disturbing the system. Non-destructive methods that do not interfere with system dynamics have been developed in the past. These methods, however, have tended to be cumbersome or inaccurate at low concentrations. A new experimental approach has been developed to measure gaseous diffusion in free air and through porous materials. The method combines the traditional non steady-state laboratory methodology with resonant acoustic gas analysis. A phase-locked-loop (PLL) resonance frequency tracker is combined with a thermally insulated copper resonator. A piston sealed with a metal bellows excites the fundamental standing wave resonance of the resonator. The PLL maintains a constant phase difference (typically 90§) between the accelerometer mounted on the piston and a microphone near the piston to track the resonance frequency in real time. A capillary or glass bead filled core is fitted into an o-ring sealed opening at the end of the resonator opposite the bellows. The rate at which the tracer gas is replaced by air within the resonator is controlled by the diffusion coefficient of the gas in free air through the capillary (DA) or by the effective diffusion coefficient of the gas through the core (De). The mean molecular weight of the gas mixture in the resonator is directly determined six times each minute from the ratio of the absolute temperature to the square of the fundamental acoustic resonance frequency. Average system stability (temperature divided by frequency squared) is better than 350 ppm. DA values for a 0.3-inch diameter capillary were in excellent agreement with published values. De values for porous media samples (0.5 mm glass beads) of four different lengths (1 through 4 inches) using three different tracer gases (He, CH4, Kr) will be reported. Comments will be offered regarding tracer gas selection and device orientation and their effect on experimental results. [Work supported by the Office of Naval Research.

The Science Teachers and Their way of Thinking about Astronomy. (Spanish Title: Los Profesores de Ciencias y Sus Formas de Pensar la Astronomía.) Os Professores de Ciências e Suas Formas de Pensar a Astronomia

NASA Astrophysics Data System (ADS)

Leite, Cristina; Hosoume, Yassuko

2007-12-01

The research presented in this article is about the way science teachers from Elementary School think about astronomical elements. Its methodology is based on semi-structured interviews, which were video recorded. The research is centered in a three-dimensional perspective of astronomical Earth, the Sun, the Moon, the planets and the stars, and also the conceptions about sky and Universe. The esults indicate a Universe that contains: Sun, stars, planets and Moon; where the Solar System is a little part of the whole. Sometimes they think that the Solar System is the Universe. The objects are in the sky or in the Universe, which, for many of them, is only the space above the Earth. The flat shape of astronomical objects and the spatial structure of the Universe are striking features. Many of them think that Sun and stars are different: the Sun is a hot object and the stars are cold ones. These results worry us and they certainly indicate how urgent it is to plan Professional Development in Astronomy for teachers, after all the PCN's emphasize that this subject is important to be taught. El objeto de investigación de este artículo es la manera de pensar sobre los elementos de la Astronomía de los profesores de Ciencias en la enseñanza fundamental. La metodología consiste en entrevistas semi-estructuradas, filmadas en video y centradas en la tridimensionalidad de los elementos astronómicos, para posibilitar un mapeamiento de las concepciones sobre las formas y dimensiones de la Tierra, del Sol, de la Luna, de los planetas y de las estrellas, como también de la concepción de cielo y de Universo en su totalidad. Los resultados indican un Universo conteniendo: Sol, estrellas, planetas y Luna, donde el Sistema Solar se ubica como parte. Algunas veces, el Universo es concebido como el propio Sistema Solar. Los objetos están en el cielo o en el Universo, que, para muchos, se restringe al espacio que está arriba de la Tierra. La forma plana de los objetos astronómicos y la estructura espacial del montaje del Universo son características fundamentales. Muchos indican Sol y estrellas como cosas distintas: el Sol es un objeto caliente y las estrellas son frías. Esos resultados nos preocupan y ciertamente señalan una urgencia de programas de formación continuada para profesores en el contenido de astronomía, pues los PCN's (Parámetros Curriculares Nacionales) recomiendan con énfasis la enseñanza de este contenido. O modo de pensar dos professores de Ciências do ensino fundamental sobre os elementos da Astronomia é o objeto de pesquisa presente neste artigo, cuja metodologia consiste em entrevistas semiestruturadas, filmadas em vídeo e centradas numa perspectiva tridimensional dos elementos astronômicos, possibilitando um mapeamento das concepções das formas e das dimensões da Terra, do Sol, da Lua, dos planetas e das estrelas, bem como da concepção de céu e de Universo como um todo. Os resultados indicam um Universo contendo: Sol, estrelas, planetas e Lua, onde o Sistema Solar é parte do todo. Algumas vezes o Universo é concebido como o próprio Sistema Solar. Os objetos estão no céu ou no Universo o qual, para muitos, se restringe ao espaço que está acima da Terra. A forma plana dos objetos astronômicos e a estrutura espacial da montagem do Universo são características marcantes. Muitos indicam Sol e estrelas como coisas diferentes: Sol é um objeto quente e as estrelas são frias. Esses resultados nos preocupam e certamente sinalizam uma urgência de programas de formação continuada para professores no conteúdo de astronomia, uma vez que os PCN's indicam fortemente o ensino desse conteúdo.

Difficulties of First Years Elementary School Teachers with the Teaching of Astronomy. (Breton Title: Dificuldades de Professores dos Anos Iniciais do Ensino Fundamental em Relação ao Ensino da Astronomia. ) Dificultades de LOS Profesores de los Primeros Años de la Escuela Primaria en Relación a la Enseñanza de la Astronomía

NASA Astrophysics Data System (ADS)

Langhi, Rodolfo; Nardi, Roberto

2005-12-01

This paper reports Primary School teachers' discourses analysis about their difficulties related to the teaching of Astronomy. It reports partial data of a master's level research carried out in the last two years, named "An exploratory study for inserting Astronomy in primary school teachers' education" (LANGHI, 2004). The study took into consideration students' and teachers' common sense conceptions about astronomical phenomena, conceptual mistakes in textbooks, and Astronomy's suggestions given by the PCN (Parâmetros Curriculares Nacionais - The Brazilian National Curriculum Standards). The paper aims to characterize teachers' difficulties, in order to provide subsides to the implementation of an initial or continuing education program. This study is justified by the fact that courses plans like these only will be adapted to the teacher's (and students') reality, if there is a primary investigation about what the teachers really need to know about Astronomy. This fact was possible here by the enunciations interpretation of a teachers' sample using semi-structured interviews, according to discourse analysis procedures. The research outcomes show difficulties related to factors like: those of personal order, methodological, on teacher's formation, educational infrastructure and other related to information sources for educators. Este artigo, que relata as dificuldades de professores em relação ao ensino da Astronomia, faz parte de um estudo exploratório para a inserção da Astronomia na formação de professores dos anos iniciais do Ensino Fundamental. Esse estudo leva em consideração as concepções alternativas de alunos e professores sobre fenômenos astronômicos, os erros conceituais em livros didáticos e as sugestões de conteúdos de Astronomia constantes nos PCN (Parâmetros Curriculares Nacionais). Caracterizar as dificuldades dos professores é a questão central deste texto, apontando para o objetivo de contribuir com subsídios para um futuro programa de formação continuada neste tema. O estudo se justifica mediante o fato de que planejamentos de cursos como estes só se adequarão à realidade do professor (e do aluno) se houver uma investigação antecipada sobre o que os docentes precisam saber e saber fazer a respeito da Astronomia, o que se concretizou em nosso caso pela interpretação dos discursos de uma amostra de professores coletados através de entrevistas semi-estruturadas, utilizando para interpretação os princípios e métodos da análise do discurso em sua linha francesa. Os resultados da pesquisa indicaram dificuldades de ordem pessoal, metodológica, de formação, de infra-estrutura e outras relacionadas às fontes de informações para docentes. Este artículo que relata las dificultades de los profesores en relación a la enseñanza da laAstronomía es parte de un estudio preliminar para la implantación dela Astrnomía enla formación de profesores de ls primeros años del ciclo primario.El estudio considera las concepciones alternativas de alumnos y profesores respecto a los fenómenos astronómicos, los errores conceptuales en los libros didácticos y las sugerencias de contenidos de Astronomía que constan en los Parámetros Curriculares Nacionales del Brasil. Caracterizar las dificultades de los profesores constituye la cuestión central de este texto, apuntando para el objetivo de contribuir para un futuro programa de educación contínua en este tema. El estudio se justifica mediante el hecho que la planificación de cursos de este tipo solo se adecuarán a la realidade del profesor (y del alumno) si existe una investigación anterior a respecto de lo que los docentes precisan saber y saber realizar en Astronomía, lo cual se concretó en nuestro caso por medio de la interpretación de los discursos de una muestra de profesores obtenidos através de entrevistas semiestructuradas, utilizand para esta interpretación los principios y métodos de análisis del discurso en su línea francesa. Los resultados mostraron dificultades de orden personal, metodológica, formativa, de infraestructura y otras relacionadas a las fuentes de información para los docentes.

Anisotropy of MHD Turbulence at Low Magnetic Reynolds Number

NASA Technical Reports Server (NTRS)

Zikanov, O.; Vorobev, A.; Thess, A.; Davidson, P. A.; Knaepen, B.

2004-01-01

Turbulent fluctuations in MHD flows are known to become dimensionally anisotropic under the action of a sufficiently strong magnetic field. We consider the technologically relevant case of low magnetic Reynolds number and apply the method of DNS of forced flow in a periodic box to generate velocity fields. The analysis based on different anisotropy characteristics shows that the dimensional anisotropy is virtually scale-independent. We also find that, except for the case of very strong magnetic field, the flow is componentally isotropic. Its kinetic energy is practically uniformly distributed among the velocity components.

Adapting Features from the SIOP Component: Lesson Delivery to English Lessons in a Colombian Public School (Adaptación de las características del componente de SIOP: Desarrollo de clase, en las clases de inglés en un colegio público colombiano)

ERIC Educational Resources Information Center

Rativa Murillo, Hollman Alejandro

2013-01-01

Despite some school efforts to offer students the best second language learning, English language lessons are often taught with an overuse of the mother tongue. Hence, an action research project was conducted in order to discover how to adapt some features of the Sheltered Instruction Observation Protocol (SIOP) component: Lesson delivery, for the…

A Conserved Endocrine Mechanism Controls the Formation of Dauer and Infective Larvae in Nematodes

PubMed Central

Ogawa, Akira; Streit, Adrian; Antebi, Adam; Sommer, Ralf J.

2009-01-01

Summary Under harsh environmental conditions Caenorhabditis elegans larvae undergo arrest and form dauer larvae that can attach to other animals to facilitate dispersal[1]. It has been argued that this phenomenon, called phoresy, represents an intermediate step towards parasitism[2, 3]. Indeed, parasitic nematodes invade their hosts as infective larvae, a stage that shows striking morphological similarities to dauer larvae[1]. While the molecular regulation of dauer entry in C. elegans involves insulin and TGF-ß signaling[4-8], studies of TGF-ß orthologues in parasitic nematodes did not provide evidence for a common origin of dauer and infective larvae[9-14]. To identify conserved candidate regulators between Caenorhabditis and parasitic nematodes we used an evolutionary approach involving Pristionchus pacificus as intermediate. We show by mutational and pharmacological analysis that Pristionchus and Caenorhabditis share the dafachronic acid-DAF-12 system as core endocrine module for dauer formation. One of the dafachronic acids, Δ7-DA, has a conserved role in the mammalian parasite Strongyloides papillosus where it controls entry into the infective stage. Application of Δ7-DA blocks formation of infective larvae and results in the generation of free-living animals. The conservation of this small molecule ligand represents a fundamental link between dauer and infective larvae and might provide a general strategy for nematode parasitism. PMID:19110431

Selenoproteins and maternal nutrition.

PubMed

Pappas, A C; Zoidis, E; Surai, P F; Zervas, G

2008-12-01

Selenium (Se) is an essential trace element of fundamental importance to health due to its antioxidant, anti-inflammatory and chemopreventive properties attributed to its presence within at least 25 selenoproteins (Sel). Sel include but not limited to glutathione peroxidases (GPx1-GPx6), thioredoxin reductases (TrxR1-TrxR3), iodothyronine deiodinases (ID1-ID3), selenophosphate synthetase 2 (SPS2), 15-kDa Sel (Sel15), SelH, SelI, SelK, SelM, SelN, SelO, SelP, SelR, SelS, SelT, SelV, SelW, as well as the 15-kDa Sel (Fep15), SelJ and SelU found in fish. In this review, we describe some of the recent progress in our understanding of the mechanisms of Sel synthesis. The impact of maternal Se intake on offspring is also discussed. The key regulatory point of Sel synthesis is Se itself, which acts predominantly at post-transcriptional levels, although recent findings indicate transcriptional and redox regulation. Maternal nutrition affects the performance and health of the progeny. Both maternal and offspring Se supplementations are essential for the antioxidant protection of the offspring. Prenatal Se supplementation provides an effective antioxidant system that is already in place at the time of birth while, postnatal Se supplementation becomes the main determinant of progeny Se status after the first few days of progeny life.

2A self-cleaving peptide-based multi-gene expression system in the silkworm Bombyx mori

PubMed Central

Wang, Yuancheng; Wang, Feng; Wang, Riyuan; Zhao, Ping; Xia, Qingyou

2015-01-01

Fundamental and applied studies of silkworms have entered the functional genomics era. Here, we report a multi-gene expression system (MGES) based on 2A self-cleaving peptide (2A), which regulates the simultaneous expression and cleavage of multiple gene targets in the silk gland of transgenic silkworms. First, a glycine-serine-glycine spacer (GSG) was found to significantly improve the cleavage efficiency of 2A. Then, the cleavage efficiency of six types of 2As with GSG was analyzed. The shortest porcine teschovirus-1 2A (P2A-GSG) exhibited the highest cleavage efficiency in all insect cell lines that we tested. Next, P2A-GSG successfully cleaved the artificial human serum albumin (66 kDa) linked with human acidic fibroblast growth factor (20.2 kDa) fusion genes and vitellogenin receptor fragment (196 kD) of silkworm linked with EGFP fusion genes, importantly, vitellogenin receptor protein was secreted to the outside of cells. Furthermore, P2A-GSG successfully mediated the simultaneous expression and cleavage of a DsRed and EGFP fusion gene in silk glands and caused secretion into the cocoon of transgenic silkworms using our sericin1 expression system. We predicted that the MGES would be an efficient tool for gene function research and innovative research on various functional silk materials in medicine, cosmetics, and other biomedical areas. PMID:26537835

Enzymatic hydrolysis of Grass Carp fish skin hydrolysates able to promote the proliferation of Streptococcus thermophilus.

PubMed

Wang, Xiao-Nan; Qin, Mei; Feng, Yu-Ying; Chen, Jian-Kang; Song, Yi-Shan

2017-09-01

The promotion effect on proliferation of Streptococcus thermophilus by enzymatic hydrolysates of aquatic products was firstly studied. The effect of influencing factors of the hydrolysis on the growth of S. thermophilus was investigated. Grass Carp fish skin was hydrolysed to peptides by enzymatic hydrolysis using protease ProteAX, and for the S. thermophilus growth, the optimal enzymatic hydrolysis conditions were temperature of 60 °C, initial pH of 9.0, enzyme concentration of 10 g kg -1 , hydrolysis time of 80 min, and ratio of material to liquid of 1:2. The Grass Carp fish skin hydrolysate (GCFSH) prepared under the optimum conditions was fractionated to five fragments (GCFSH 1, GCFSH 2, GCFSH 3, GCFSH 4, GCFSH 5) according to molecular weight sizes, in which the fragments GCFSH 4 and GCFSH 5, with molecular weights of less than 1000 Da, significantly promoted the growth of S. thermophilus. The hydrolysis process of Grass Carp fish skin can be simplified, and the peptides with molecular weights below 1000 Da in the hydrolysates are the best nitrogen source for proliferation of S. thermophilus. This work can provide a fundamental theoretical basis for the production of multi-component functional foods, especially in milk drinks or yogurt. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The Understanding of Astronomy Concepts by Students from Basic Education of a Public School. (Spanish Title: El Entendimiento de Conceptos de Aastronmía Por Los Alumnos de Educación Básica en Una Escuela Pública.) O Entendimento de Conceitos de Astronomia Por Alunos da Educação Básica: O Caso de Uma Escola Pública Brasileira

NASA Astrophysics Data System (ADS)

Iria Machado, Daniel; dos Santos, Carlos

2011-07-01

We present the results obtained in a research on the comprehension of basic astronomical concepts, in which 561 students from fifth grade middle school to third grade high school of a public school of the city of Foz do Iguaçu (Brazil) took part. A test with 20 multiple-choice questions was applied to indentify the most common conceptions expressed by the students. This test was elaborated based on the literature about misconceptions and covered the following topics: the day-night cycle; the time zones; the seasons of the year; the phases of the Moon; the movement of the Moon; the apparent movement of the Sun in the celestial sphere; the eclipses; the dimensions and distances in the Universe; the brightness of the stars and its observation from Earth. Though a small progress was verified in the proportion of scientifically acceptable answers when comparing the eighth grade of middle school to the fifth, and the third grade of high school to the first, there was an overall predominance of alternative conceptions regarding most of the explored subjects, which persisted up to the last year of secondary school. The comparison to data found in this research made in other socio-cultural contexts revealed, in many aspects, similar notions and difficulties revealed by the students. Se presentan los resultados de una investigación sobre la comprensión de conceptos astronómicos básicos, en la cual participaron 561 estudiantes que cursaban entre el quinto grado de la enseñanza primaria y el tercer año de la enseñanza secundaria de una escuela pública de la ciudad de Foz do Iguaçu (Brasil). Se utilizó un test de 20 preguntas de opción múltiple para identificar las concepciones más comunes expresadas por los estudiantes. Este instrumento de recolección de datos se desarrolló en base a la literatura sobre las concepciones alternativas y trató los siguientes temas: el ciclo día-noche, los husos horarios, las estaciones del año, las fases de la Luna, el movimiento de la Luna, el movimiento aparente del Sol sobre la esfera celeste, los eclipses, las dimensiones y las distancias en el Universo, el brillo de las estrellas y su observación de la Tierra. Si bien ha habido un pequeño progreso en la proporción de respuestas aceptables científicamente cuando se cotejó el octavo grado de la enseñanza primaria con el quinto, y el último año de la enseñanza secundaria con el primero, se observó un predominio de las concepciones alternativas en relación a la mayoría de los temas explorados, que continuó hasta los últimos años de la educación básica. Una comparación con los datos encontrados en investigaciones realizadas en otros contextos socioculturales revelaron, en muchos aspectos, conceptos y dificultades similares expresadas por los estudiantes. Apresentam-se os resultados de uma investigação sobre a compreensão de conceitos astronômicos básicos, da qual participaram 561 estudantes da quinta série do Ensino Fundamental ao terceiro ano do Ensino Médio de uma escola pública da cidade de Foz do Iguaçu. Um teste com 20 questões de múltipla escolha foi aplicado para identificar as concepções mais comuns expressadas pelos alunos. Esse instrumento de coleta de dados foi elaborado com base na literatura sobre concepções alternativas e abordou os seguintes temas: o ciclo dia-noite; os fusos horários; as estações do ano; as fases da Lua; o movimento da Lua; o movimento aparente do Sol na esfera celeste; os eclipses; as dimensões e distâncias no Universo; o brilho das estrelas e sua observação da Terra. Embora se tenha verificado um pequeno progresso na proporção de respostas cientificamente aceitáveis ao se cotejar a oitava série do Ensino Fundamental com a quinta, e a terceira série do Ensino Médio com a primeira, houve o predomínio de concepções alternativas em relação à maior parte dos temas explorados, as quais persistiram até o último ano da Educação Básica. A comparação com dados encontrados em investigações realizadas em outros contextos socioculturais revelaram, em muitos aspectos, noções e dificuldades similares manifestadas pelos estudantes.

Multiscale Modeling: A Review

NASA Astrophysics Data System (ADS)

Horstemeyer, M. F.

This review of multiscale modeling covers a brief history of various multiscale methodologies related to solid materials and the associated experimental influences, the various influence of multiscale modeling on different disciplines, and some examples of multiscale modeling in the design of structural components. Although computational multiscale modeling methodologies have been developed in the late twentieth century, the fundamental notions of multiscale modeling have been around since da Vinci studied different sizes of ropes. The recent rapid growth in multiscale modeling is the result of the confluence of parallel computing power, experimental capabilities to characterize structure-property relations down to the atomic level, and theories that admit multiple length scales. The ubiquitous research that focus on multiscale modeling has broached different disciplines (solid mechanics, fluid mechanics, materials science, physics, mathematics, biological, and chemistry), different regions of the world (most continents), and different length scales (from atoms to autos).

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness

NASA Technical Reports Server (NTRS)

Lucot, James B.; Crampton, George H.; Matson, Wayne R.; Gamache, Paul H.

1989-01-01

The cerebrospinal fluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

CURRENT SITUATION OF MEDICINE III AND CHALLENGES.

PubMed

Ferreira, Lydia Masako

2015-01-01

Describe the current situation of the area Medicine III of CAPES and detect challenges for the next four years of evaluation. The area's documents and reports of meetings were read from 2004 to 2013 Medicine III Capes as well as reports and evaluation form of each Postgraduate Program (PPG) of the area and the sub-page of the area from the Capes website. The data relating to the evaluation process, the assessment form and faculty, student and scientific production data of all of Post-Graduate Programs of Medicine III were computed and analyzed. From these data were detected the challenges of the area for the next four years (2013-2016). Among the 3,806 PPG, Medicine III had 41 PPG during last triennial evaluation and progressed from 18% to 43% of PPG very good or more concept (triennium 2001-2003 and 2010-2012). Most PPG were located in the South-East region (32), three in the South and two in the North-East. There was no PPG in North or Central-West regions. In 2013 and 2014 there were four approved Professional Master Degree Programs and one Master (M) and Doctorate (PhD). The average of permanent professors was 558 teachers with about three students/professor. The number of PhD graduates has increased as well as the reason PhD/MD. The proportion of in high impact periodicals (A1, A2, B1 and B2) jumped from 30% to 50% demonstrating positive community response to the policy area. The challenges identified were: decrease regional asymmetry, increase the number of masters and doctors of excellence, reassessment of Brazilian journals, stimulate and set internationalization indicators, including post-doctors and definition of its indicators, the PPG nucleation analysis, PPG 3x3, include primary and secondary education, professional master and indicators of technological scientific production and solidarity. Medicine III has been scientifically consolidated and their scientific researchers demonstrated maturity reaching a high level and matched to areas of greatest tradition and history. For the maintenance and advancement of the area some challenges and goals were established to be developed in the period from 2013 to 2016. Descrever a situação atual da área Medicina III da Capes e detectar os desafios para o próximo quadriênio de avaliação. Os documentos e relatórios de reuniões de área a partir de 2004 até 2013 da Medicina III da Capes foram lidos assim como os relatórios e as fichas de avaliação de cada Programa de Pós Graduação (PPG) da área e a subpágina da área no site da Capes. Os dados referentes ao Processo de Avaliação, à Ficha de Avaliação e aos dados do Corpo Docente, Discente e Produção científica de todos os PPG da Medicina III foram computados e analisados. A partir desses dados foram detectados os desafios da área para o próximo quadriênio (2013-2016). Dentre os 3.806 PPG, a Medicina III apresentava 41 PPG durante última avaliação trienal e evoluiu de 18% para 43% de PPG > conceito muito bom (Triênios 2001-2003 e 2010-2012). A maioria dos PPG se localizavam na Região Sudeste (32), três no Sul e dois no Nordeste. Não havia nenhum PPG no Norte ou Centro-Oeste. Em 2013 e 2014 foram aprovadas quatro mestrados profissionais e um mestrado e doutorado acadêmico. A média de docente permanente no triênio foi de 558 docentes com cerca de três alunos titulados/docente. O número de doutores titulados tem aumentado assim como a razão Doutorado/Mestrado. A proporção de publicações em periódicos de maior impacto (A1, A2, B1 e B2) saltou de 30% para 50% demonstrando resposta positiva da comunidade à política da área. Os desafios detectados foram: diminuir assimetria regional, elevar o número de mestres e doutores de excelência, reavaliação das revistas nacionais, estimular e definir indicadores de internacionalização, inclusão de pós-doutores e definição de seus indicadores, análise da nucleação do PPG, PPG 3x3, inclusão ensino médio e fundamental, mestrado profissional e indicadores da produção científico-tecnológica e solidariedade. A Medicina III tem se consolidado cientificamente e seus pesquisadores demonstraram maturidade científica chegando a um patamar elevado e igualado às áreas de maior tradição e história. Para a manutenção e avanço da área alguns desafios e metas foram traçadas para serem desenvolvidas no quadriênio 2013-2016.

Improvement Science: conceptual and theoretical foundations for its application to healthcare quality improvement.

PubMed

Portela, Margareth Crisóstomo; Lima, Sheyla Maria Lemos; Martins, Mônica; Travassos, Claudia

2016-11-03

The development and study of healthcare quality improvement interventions have been reshaped, moving from more intuitive approaches, dominated by biomedical vision and premised on easy transferability, to gradually acknowledge the need for more planning and systematization, with greater incorporation of the social sciences and enhancement of the role of context. Improvement Science has been established, with a conceptual and methodological framework for such studies. Considering the incipient of the debate and scientific production on Improvement Science in Brazil, this article aims to expound its principal conceptual and theoretical fundamentals, focusing on three central themes: the linkage of different disciplines; recognition of the role of context; and the theoretical basis for the design, implementation, and evaluation of interventions. Resumo: O desenvolvimento e estudo de intervenções para a melhoria do cuidado de saúde tem ganhado novo contorno, movendo-se das abordagens mais intuitivas, com domínio da visão biomédica e assentadas no pressuposto de fácil transferibilidade, para gradativamente reconhecer a necessidade de mais planejamento e sistematização, com maior incorporação das ciências sociais e valorização do papel do contexto. A Ciência da Melhoria do Cuidado de Saúde vem se estabelecendo, propiciando referencial conceitual e metodológico para tais estudos. Considerando a incipiência do debate e produção sobre Ciência da Melhoria do Cuidado de Saúde no Brasil, este artigo objetiva discorrer sobre as principais bases conceituais e teóricas que a sustentam, com foco em três temas centrais: a articulação de diferentes disciplinas; o reconhecimento do papel do contexto; e o embasamento teórico para o desenho, implementação e avaliação das intervenções.

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

PubMed Central

Randall, Patrick A.; Lee, Christie A.; Nunes, Eric J.; Yohn, Samantha E.; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V. Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E.; Correa, Merce; Salamone, John D.

2014-01-01

Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients. PMID:24937131

The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

PubMed

Randall, Patrick A; Lee, Christie A; Nunes, Eric J; Yohn, Samantha E; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Merce; Salamone, John D

2014-01-01

Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.

Usina de ciências: um espaço pedagógico para aprendizagens múltiplas

NASA Astrophysics Data System (ADS)

Martin, V. A. F.; Poppe, P. C. R.; Orrico, A. C. P.; Pereira, M. G.

2003-08-01

Entendemos que o Ensino de Astronomia é especialmente apropriado para motivar os alunos e aprofundar conteúdos em diversas áreas do conhecimento, pois envolve temas ligados à Física, Matemática, Química, Computação, Tratamento de Imagens e Instrumentação de Alta Precisão, além daqueles pertinentes as áreas de Geografia, História e Antropologia. Contudo, apesar do caráter interdisciplinar que esta ciência possui, a realidade atual é que a maioria dos professores em sala de aula não foram devidamente capacitados, durante o período de formação acadêmica, para ministrar conteúdos de Astronomia nos atuais Ensinos Fundamental e Médio. Neste trabalho, discutiremos de maneira ampla, num primeiro momento, a realidade do atual ensino de ciências praticado no Estado da Bahia, apontando por dependência administrativa, o crescimento e a redução do número de escolas, da taxa de analfabetismo por faixa etária, da escolarização, do atendimento, da aprovação, reprovação e abandono, de equipamentos e laboratórios e o grau de formação dos nossos atuais professores em pleno exercício de atividade docente. Num segundo momento, discutiremos o papel do Observatório Astronômico Antares/UEFS dentro desse contexto, ou seja, suas ações implementadas ao longo dos últimos anos e em particular, o recente projeto de extensão Ensino e Difusão de Astronomia, financiado pela Fundação Vitae, que procura traduzir no lúdico, no brincar de ciências, um espaço pedagógico para aprendizagens múltiplas. Neste, o papel do professor multiplicador associado ao laboratório de kits didáticos, de fácil construção e manipulação (alguns dos quais serão mostrados), perfazem os principais veículos para o desenvolvimento de conhecimentos, atitudes, habilidades e valores que preparam os nossos alunos para a carreira técnico-científica e para sua participação crítica e criativa na Sociedade.

Chronic and asymptomatic diseases influence the control of hypertension treatment in primary care.

PubMed

Pierin, Angela Maria Geraldo; Silva, Stael Silvana Bagno Eleutério da; Colósimo, Flávia Cortez; Toma, Gabriela de Andrade; Serafim, Talita de Souza; Meneghin, Paolo

2016-01-01

To identify the association between blood pressure control and the following variables: a) bio-social and lifestyle characteristics of hypertensive patients; and b) factors related to the antihypertensive treatment. This is an exploratory study with 290 people with hypertension from primary care. We used a specific instrument, self-administered, with 21 questions on factors that can hinder treatment, divided into four dimensions: medication, socioeconomic, institutional and personal beliefs. We adopted a significance level of p <0.05. The control of blood pressure was associated (p <0.05) with female gender, Caucasian ethnicity, primary/secondary education, not drinking alcohol, higher income and regular physical activity. Regarding the factors that can hinder treatment, there was association of hypertension control with only two questions: "feel nothing" and "have to do treatment for life". Sociodemographic variables and beliefs concerning the absence of symptoms and chronicity of the disease influenced the control of hypertension and should be considered in the adherence process to the treatment. Identificar a associação entre o controle da pressão arterial e as seguintes variáveis: a) características biossociais e hábitos de vida dos hipertensos; e b) fatores relacionados ao tratamento anti-hipertensivo. Realizou-se estudo exploratório com 290 hipertensos da atenção primária. Utilizou-se de instrumento específico, autoaplicável, com 21 questões sobre fatores que podem dificultar o tratamento, divididas em quatro domínios: medicamentos, socioeconômico, institucional e crenças pessoais. Adotou-se nível de significância de p < 0,05. O controle da pressão arterial se associou (p < 0,05) com sexo feminino, etnia branca, ensino fundamental/médio, não ingerir bebida alcoólica, maior renda e atividade física regular. Quanto aos fatores que podem dificultar o tratamento, houve associação do controle com apenas duas questões: "não sentir nada" e "ter que fazer tratamento para vida toda". Variáveis sociodemográficas e crenças relativas à ausência de sintomatologia e cronicidade da doença influenciaram o controle dos hipertensos e devem ser consideradas no processo de adesão ao tratamento.

Questões mais freqüentes na área de astronomia

NASA Astrophysics Data System (ADS)

Segundo, H. A. S.; Garcia, G. C.; Caretta, C. A.; Lima, F. P.

2003-08-01

É amplamente reconhecido que as pessoas em geral têm grande fascínio e interesse pela Astronomia. Por outro lado, o conteúdo dessa área incluído no ensino formal está longe de ser abrangente e suficiente para suprir a demanda. Esse interesse permite otimizar a divulgação e o ensino não formal de Astronomia aliando a adequação do conteúdo à expectativa das pessoas. Nesse intuito, nosso trabalho busca mapear que assuntos da Astronomia despertam mais a atenção e o interesse das pessoas e o quanto disso é estimulado pela mídia, que freqüentemente aproveita-se desse interesse de forma sensacionalista, trazendo contribuições positivas e negativas. Para esta avaliação, utilizamos as pesquisas específicas e de caracterização do público que freqüentou o MAst nos anos de 2001 a 2003, pesquisa das matérias de Astronomia veiculadas na mídia escrita da cidade do Rio de Janeiro no mesmo período, além da base de dados do programa Pergunte a um astrônomo, realizado no Observatório Nacional nos anos de 1997 a 1999. Para a análise dos dados, dividimos as perguntas em dez categorias, cada uma com suas subcategorias, tomando como referência as divisões, comissões e grupos de trabalho da IAU. Apresentamos neste trabalho os resultados dessa pesquisa, que incluem, entre outros, a predominância de questões nas categorias Observação do Céu e Sistemas Planetários enquanto nos jornais dominam as notícias de Sistemas Planetários e Espaço & Astronáutica. Outro resultado interessante indicou que as dúvidas de crianças do ensino fundamental se concentram em algumas categorias enquanto as questões de adultos são mais distribuídas por todas as categorias. Os resultados dessa pesquisa serão aplicados diretamente no aperfeiçoamento das atividades do Programa de Observação de Céu, bem como na elaboração de novos projetos e eventos realizados no MAst.

Ensino de astronomia no 1o. e 2o. ciclos do nível fundamental e na educação de jovens e adultos: exemplos e discussões

NASA Astrophysics Data System (ADS)

Queiroz, A. S. B.; Jafelice, L. C.

2003-08-01

Tem-se constatado uma preocupante carência no ensino de astronomia nos diversos níveis de escolaridade. Neste trabalho discutimos várias práticas didático-pedagógicas que vimos desenvolvendo para crianças, jovens e adultos em processo de alfabetização, visando contribuir para reparar aquela carência. Propomos uma metodologia que incorpora as recentes exigências das políticas públicas educacionais, estimula o desenvolvimento de textos e materiais instrucionais, é compatível com a realidade desse público e é adaptável às respectivas faixas etárias. A observação do céu sempre esteve presente na vida de nossos antepassados, dando suporte à compreensão do ser humano como integrante da natureza. Visamos com este trabalho suprir a deficiência encontrada para se tratar a relação do ser humano com o céu, no ambiente escolar. Os resultados são animadores e envolvem práticas e textos que desenvolvemos e atividades realizadas pelos alunos. No primeiro grupo destacamos o desenvolvimento de várias práticas: "viagem aos planetas" (construímos o "foguete", os planetas em escala, contamos história e redigimos texto de orientação para os professores); "gnômon humano" (os próprios corpos dos alunos são usados para registrar o movimento aparente do Sol); "crateras da Lua" (concretização de "meteoritos" e "solo lunar" de gesso e exploração da relação entre energia cinética do bólido e tamanho da cratera formada); etc. No segundo grupo, produções de desenhos e redações e discussões dos alunos após a realização de cada prática, revelam que estas têm se mostrado muito eficientes, tanto para estimular a imaginação e a fantasia dos envolvidos, como para trabalhar-se habilidades, competências e conteúdos relacionados à astronomia, segundo uma perspectiva interdisciplinar contextualizada. (PPGECNM/UFRN; NUPA/USP; Temáticos/FAPESP)

Molecular excitonic seesaws.

PubMed

Wilhelm, Philipp; Schedlbauer, Jakob; Hinderer, Florian; Hennen, Daniel; Höger, Sigurd; Vogelsang, Jan; Lupton, John M

2018-04-17

The breaking of molecular symmetry through photoexcitation is a ubiquitous but rather elusive process, which, for example, controls the microscopic efficiency of light harvesting in molecular aggregates. A molecular excitation within a π-conjugated segment will self-localize due to strong coupling to molecular vibrations, locally changing bond alternation in a process which is fundamentally nondeterministic. Probing such symmetry breaking usually relies on polarization-resolved fluorescence, which is most powerful on the level of single molecules. Here, we explore symmetry breaking by designing a large, asymmetric acceptor-donor-acceptor (A 1 -D-A 2 ) complex 10 nm in length, where excitation energy can flow from the donor, a π-conjugated oligomer, to either one of the two boron-dipyrromethene (bodipy) dye acceptors of different color. Fluorescence correlation spectroscopy (FCS) reveals a nondeterministic switching between the energy-transfer pathways from the oligomer to the two acceptor groups on the submillisecond timescale. We conclude that excitation energy transfer, and light harvesting in general, are fundamentally nondeterministic processes, which can be strongly perturbed by external stimuli. A simple demonstration of the relation between exciton localization within the extended π-system and energy transfer to the endcap is given by considering the selectivity of endcap emission through the polarization of the excitation light in triads with bent oligomer backbones. Bending leads to increased localization so that the molecule acquires bichromophoric characteristics in terms of its fluorescence photon statistics.

Perception of speech in noise: neural correlates.

PubMed

Song, Judy H; Skoe, Erika; Banai, Karen; Kraus, Nina

2011-09-01

The presence of irrelevant auditory information (other talkers, environmental noises) presents a major challenge to listening to speech. The fundamental frequency (F(0)) of the target speaker is thought to provide an important cue for the extraction of the speaker's voice from background noise, but little is known about the relationship between speech-in-noise (SIN) perceptual ability and neural encoding of the F(0). Motivated by recent findings that music and language experience enhance brainstem representation of sound, we examined the hypothesis that brainstem encoding of the F(0) is diminished to a greater degree by background noise in people with poorer perceptual abilities in noise. To this end, we measured speech-evoked auditory brainstem responses to /da/ in quiet and two multitalker babble conditions (two-talker and six-talker) in native English-speaking young adults who ranged in their ability to perceive and recall SIN. Listeners who were poorer performers on a standardized SIN measure demonstrated greater susceptibility to the degradative effects of noise on the neural encoding of the F(0). Particularly diminished was their phase-locked activity to the fundamental frequency in the portion of the syllable known to be most vulnerable to perceptual disruption (i.e., the formant transition period). Our findings suggest that the subcortical representation of the F(0) in noise contributes to the perception of speech in noisy conditions.

[Not Available].

PubMed

Vales Montero, Marta; Chavarría Cano, Beatriz; Martínez Ginés, María Luisa; Díaz Otero, Fernando; Velázquez Pérez, José Miguel; Cuerda Compes, María Cristina; Bretón Lesmes, Irene

2016-07-19

La deficiencia de vitamina A es infrecuente en los países desarrollados. La cirugía bariátrica constituye un factor de riesgo de deficiencia de esta vitamina. Se han descrito varios casos en pacientes sometidos a técnicas con un importante componente malabsortivo, como la derivación biliopancreática. En este artículo se describe un caso de deficiencia clínica de vitamina A con manifestaciones oculares y cutáneas tras bypass gástrico y se revisan las publicaciones sobre este tema y las recomendaciones para la prevención de esta importante complicación.

Endoscopic thymectomy: a neurologist’s perspective

PubMed Central

Melfi, Franca; Maestri, Michelangelo; De Rosa, Anna; Petsa, Afroditi; Lucchi, Marco; Mussi, Alfredo

2016-01-01

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by the presence of antibodies interacting at the neuromuscular junction (NMJ), resulting in loss of strength and severe exhaustibility of striated muscles. The abnormal production of these antibodies is triggered mainly in the thymus, and hence thymectomy in MG is considered a universally recommended treatment in order to improve the symptomatologic condition of this pathology. Currently, minimally invasive thymectomy using the Da Vinci robot system is certainly one of the most innovative techniques, performed in Pisa since 2001. This approach provides a valuable alternative to the traditional thymectomy through median sternotomy. The contribution of a neurologist is fundamental for preoperative patient selection and for the peri-operative clinical assistance in both approaches. We believe that in the robotic approach, the multidisciplinary collaboration between the neurologist, thoracic surgeon and anesthetist is important in reducing perioperative complications and ensuring a higher rate of complete remission or stable clinical improvement of MG. PMID:26904430

[Aged woman's vulnerability related to AIDS].

PubMed

Silva, Carla Marins; Lopes, Fernanda Maria do Valle Martins; Vargens, Octavio Muniz da Costa

2010-09-01

This article is a systhematic literature review including the period from 1994 to 2009, whose objective was to discuss the aged woman's vulnerability in relation to Acquired Imunodeficiency Syndrome (Aids). The search for scientific texts was accomplished in the following databases: Biblioteca Virtual em Saúde, Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE). The descriptors used were vulnerability, woman and Aids. Eighteen texts were analyzed, including articles in scientific journals, thesis and dissertations. As a conclusion, it was noted that aged women and vulnerability to Aids are directly related, through gender characteristics including submission and that were built historical and socially. We consider as fundamental the development of studies which may generate publications accessible to women, in order to help them see themselves as persons vulnerable to Aids contagion just for being women.

Controlled Chemical Patterns with ThermoChemical NanoLithography (TCNL)

NASA Astrophysics Data System (ADS)

Carroll, Keith; Giordano, Anthony; Wang, Debin; Kodali, Vamsi; King, W. P.; Marder, S. R.; Riedo, E.; Curtis, J. E.

2012-02-01

Many research areas, both fundamental and applied, rely upon the ability to organize non-trivial assemblies of molecules on surfaces. In this work, we introduce a significant extension of ThermoChemical NanoLithography (TCNL), a high throughput chemical patterning technique that uses temperature-driven chemical reactions localized near the tip of a thermal cantilever. By combining a chemical kinetics based model with experiments, we have developed a protocol for varying the concentration of surface bound molecules. The result is an unprecedented ability to fabricate extremely complex patterns comprised of varying chemical concentrations, as demonstrated by sinusoidal patterns of amine groups with varying pitches (˜5-15 μm) and the replication of Leonardo da Vinci's Mona Lisa with dimensions of ˜30 x 40 μm^2. Programmed control of the chemical reaction rate should have widespread applications for a technique which has already been shown to nanopattern various substrates including graphene nanowires, piezoelectric crystals, and optoelectronic materials.

Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions

NASA Astrophysics Data System (ADS)

Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

2016-11-01

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

The Nursing Diagnosis of risk for pressure ulcer: content validation.

PubMed

Santos, Cássia Teixeira Dos; Almeida, Miriam de Abreu; Lucena, Amália de Fátima

2016-06-14

to validate the content of the new nursing diagnosis, termed risk for pressure ulcer. the content validation with a sample made up of 24 nurses who were specialists in skin care from six different hospitals in the South and Southeast of Brazil. Data collection took place electronically, through an instrument constructed using the SurveyMonkey program, containing a title, definition, and 19 risk factors for the nursing diagnosis. The data were analyzed using Fehring's method and descriptive statistics. The project was approved by a Research Ethics Committee. title, definition and seven risk factors were validated as "very important": physical immobilization, pressure, surface friction, shearing forces, skin moisture, alteration in sensation and malnutrition. Among the other risk factors, 11 were validated as "important": dehydration, obesity, anemia, decrease in serum albumin level, prematurity, aging, smoking, edema, impaired circulation, and decrease in oxygenation and in tissue perfusion. The risk factor of hyperthermia was discarded. the content validation of these components of the nursing diagnosis corroborated the importance of the same, being able to facilitate the nurse's clinical reasoning and guiding clinical practice in the preventive care for pressure ulcers. validar o conteúdo do novo diagnóstico de enfermagem, denominado risco de úlcera por pressão. trata-se de uma validação de conteúdo, com amostra composta por 24 enfermeiros especialistas no cuidado à pele, procedentes de seis diferentes hospitais do Sul e Sudeste brasileiro. A coleta de dados ocorreu por meio eletrônico, em instrumento construído pelo programa SurveyMonkey, que continha título, definição e 19 fatores de risco para o diagnóstico de enfermagem. Os dados foram analisados pelo método de Fehring e pela estatística descritiva. O projeto foi aprovado em Comitê de Ética em Pesquisa. título, definição e sete fatores de risco foram validados como "muito importante", sendo: imobilidade, pressão, fricção, cisalhamento, umidade, sensações prejudicadas e desnutrição. Dentre os demais fatores de risco, onze foram validados como "importante": desidratação, obesidade, anemia, baixo nível de albumina, prematuridade, envelhecimento, tabagismo, edema, circulação prejudicada, diminuição da oxigenação e da perfusão tissular. O fator de risco hipertermia foi descartado. a validação de conteúdo desses componentes do diagnóstico de enfermagem corroborou a importância dos mesmos, podendo facilitar o raciocínio clínico do enfermeiro, norteando a prática clínica no cuidado preventivo à úlcera por pressão. validar el contenido del nuevo diagnóstico de enfermería denominado riesgo de úlcera por presión. se trata de una validación de contenido, con muestra compuesta por 24 enfermeros especialistas en el cuidado de la piel, procedentes de seis diferentes hospitales del Sur y Sureste brasileño. La recolección de datos se realizó por medio electrónico, con un instrumento construido por el programa SurveyMonkey, que contenía: título, definición y 19 factores de riesgo para el diagnóstico de enfermería. Los datos fueron analizados por el método de Fehring y con la estadística descriptiva. El proyecto fue aprobado en el Comité de Ética en Investigación. título, definición y siete factores de riesgo fueron validados como "muy importante"; los factores fueron: inmovilidad, presión, fricción, cizallamiento, humedad, sensaciones perjudicadas y desnutrición. Entre los demás factores de riesgo, once fueron validados como "importante": deshidratación, obesidad, anemia, bajo nivel de albumina sérica, prematuridad, envejecimiento, tabaquismo, edema, circulación perjudicada, disminución de la oxigenación y perfusión tisular. El factor de riesgo hipertermia fue descartado. la validación de contenido, de esos componentes del diagnóstico de enfermería, confirmó la importancia de los mismos, lo que puede facilitar el raciocinio clínico del enfermero, orientando la práctica clínica en el cuidado preventivo de la úlcera por presión.

Removal of haloacetic acids from swimming pool water by reverse osmosis and nanofiltration.

PubMed

Yang, Linyan; She, Qianhong; Wan, Man Pun; Wang, Rong; Chang, Victor W-C; Tang, Chuyang Y

2017-06-01

Recent studies report high concentrations of haloacetic acids (HAAs), a prevalent class of toxic disinfection by-products, in swimming pool water (SPW). We investigated the removal of 9 HAAs by four commercial reverse osmosis (RO) and nanofiltration (NF) membranes. Under typical SPW conditions (pH 7.5 and 50 mM ionic strength), HAA rejections were >60% for NF270 with molecular weight cut-off (MWCO) equal to 266 Da and equal or higher than 90% for XLE, NF90 and SB50 with MWCOs of 96, 118 and 152 Da, respectively, as a result of the combined effects of size exclusion and charge repulsion. We further included 7 neutral hydrophilic surrogates as molecular probes to resolve the rejection mechanisms. In the absence of strong electrostatic interaction (e.g., pH 3.5), the rejection data of HAAs and surrogates by various membranes fall onto an identical size-exclusion (SE) curve when plotted against the relative-size parameter, i.e., the ratio of molecular radius over membrane pore radius. The independence of this SE curve on molecular structures and membrane properties reveals that the relative-size parameter is a more fundamental SE descriptor compared to molecular weight. An effective molecular size with the Stokes radius accounting for size exclusion and the Debye length accounting for electrostatic interaction was further used to evaluate the rejection. The current study provides valuable insights on the rejection of trace contaminants by RO/NF membranes. Copyright © 2017. Published by Elsevier Ltd.

Profiling of polar lipids in marine oleaginous diatom Fistulifera solaris JPCC DA0580: prediction of the potential mechanism for eicosapentaenoic acid-incorporation into triacylglycerol.

PubMed

Liang, Yue; Maeda, Yoshiaki; Yoshino, Tomoko; Matsumoto, Mitsufumi; Tanaka, Tsuyoshi

2014-05-28

The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known as the essential health supplement for humans. EPAs are mainly incorporated into glycerolipids in the microalgal cell instead of the presence as free fatty acids. Therefore, the understanding of the EPA biosynthesis including the incorporation of the EPA into glycerolipids especially triacylglycerol (TAG) is fundamental for regulating EPA content for different purposes. In this study, in order to identify the biosynthesis pathway for the EPA-containing TAG species, a lipidomic characterization of the EPA-enriched polar lipids was performed by using direct infusion electrospray ionization (ESI)-Q-TRAP-MS and MS/MS analyses. The determination of the fatty acid positional distribution showed that the sn-2 position of all the chloroplast lipids and part of phosphatidylcholine (PC) species was occupied by C16 fatty acids. This result suggested the critical role of the chloroplast on the lipid synthesis in F. solaris. Furthermore, the exclusive presence of C18 fatty acids in PC highly indicated the biosynthesis of EPA on PC. Finally, the PC-based acyl-editing and head group exchange processes were proposed to be essential for the incorporation of EPA into TAG and chloroplast lipids.

Conceptuaciones de los estudiantes de las facultades de educacion y ciencias naturales de la Universidad de Puerto Rico, recinto de Rio Piedras, acerca de la ciencia y la pseudociencia

NASA Astrophysics Data System (ADS)

Reyes Medina, Hector A.

Esta investigacion describe las conceptuaciones de los estudiantes de tercer ano o mas a nivel de bachillerato de los programas de Educacion en Ciencia y Ciencias Naturales de la Universidad de Puerto Rico, Recinto de Rio Piedras, acerca de lo establecido en la literatura para distinguir el conocimiento cientifico de las creencias pseudocientificas. Este estudio se guio por un diseno tipo encuesta transversal que permitio conocer de manera consistente las conceptuaciones de los estudiantes encuestados acerca de la Ciencia y la Pseudociencia. Ademas, permitio desarrollar inferencias estadisticas relacionadas a la poblacion de estudio, sus conceptuaciones y su inclinacion teorica en torno al Realismo y al Racionalismo cientifico moderados. El instrumento utilizado fue el Cuestionario acerca de las concepciones de la ciencia y la pseudocienca en estudiantes universitarios, Reyes (2015). Este cuestionario fue validado mediante la recopilacion de diversas fuentes de evidencias, entre estas se encuentran las evidencias basadas en el contenido, el proceso de respuesta, la estructura interna y de constructo. Tambien, se calculo el Alfa de Crombach para la escala total y para cada componente y se realizo un analisis de factores que demostro la presencia de seis componentes claramente definidos de acuerdo a lo esperado sobre las caracteristicas originales del instrumento. Las estadisticas utilizadas fueron descriptivas. Participaron 302 alumnos, de las facultades de educacion y ciencias naturales. Se encontro que las conceptuaciones de los estudiantes de ambas facultades se inclinan en un 66.2% a favor con lo establecido en el modelo teorico en torno al Realismo y al Racionalismo cientifico moderados. Sin embargo, aun hay un 33.8% de los estudiantes de ambas facultades que poseen conceptuaciones distintas al modelo teorico propuesto.

PubMed

López, Ana Cristina; Cecchetto, Eugenio; Aguirre, Ana Noemí; Ontiveros, Marina Celeste; Roitter, Claudia Valentina; Garcia, Adelaida Judith; Bernet, Jorgelina; Aguirre, Jorge Alberto

2018-03-23

El objetivo del estudio fue describir características clínicas, sociodemográficas y hábitos en adultos con diabetes mellitus y estudiar su asociación con la calidad de vida relacionada con la salud. Se seleccionó una muestra de 311 pacientes del Programa de Diabetes de una obra social universitaria, de la provincia de Córdoba. Se analizaron los datos a como proporciones y los componentes físico y mental del cuestionario SF-36® . El 57,4% alcanzó un nivel de instrucción terciario o universitario. La hipertensión arterial fue el factor de riesgo cardiovascular más prevalente (86,8%), seguida por dislipemia (50,6%) y obesidad (46,5%). El 24,8% tenía complicación macrovascular y el 29% microvascular. En el componente físico (CF) de calidad de vida las mujeres tuvieron una chance 4,2 veces mayor de reportar un valor inferior en relación a los varones. Entre los 50 y los 70 años se triplicó y los mayores de  70 años tuvieron 4 veces peor una puntuación en el CF respecto a los más jóvenes. Las complicaciones macro y microvasculares y los que reportaron menos de 2 hábitos de vida saludables tuvieron el doble de chances de puntuar por debajo del promedio general en el CF. La asociación entre complicaciones y peor calidad de vida es un motivo más para alcanzar un buen control metabólico, optimizar el manejo de factores de riesgo, evitando o retrasando la aparición de complicaciones.

Índice de vulnerabilidad de adultos mayores en Medellín, Barranquilla y Pasto.

PubMed

Cardona, Doris; Segura, Ángela; Segura, Alejandra; Muñoz, Diana; Jaramillo, Daniel; Lizcano, Douglas; Agudelo, Maite Catalina; Arango, Catalina; Morales, Santiago

2018-05-01

Introducción. La vulnerabilidad puede entenderse como la carencia de recursos materiales e inmateriales que impide el aprovechamiento de oportunidades en distintos aspectos de la vida. Estos recursos de bienestar evitan el deterioro de la calidad de vida.Objetivo. Construir un índice de vulnerabilidad con las características de los capitales físico, humano, social y funcional de los adultos mayores de tres ciudades de Colombia en el 2016, y determinar los factores asociados con esta condición.Materiales y métodos. Se hizo un estudio transversal con información primaria mediante 1.514 encuestas a personas de 60 años o más de Medellín, Barranquilla y Pasto. En la construcción del índice se usó el análisis factorial con los métodos de componentes principales y de rotación ortogonal varimax.Resultados. Las condiciones que generaban vulnerabilidad se relacionaron principalmente con el capital humano (calidad de vida, salud mental y hábitos); los demás capitales aportaron un solo componente, así: capital físico (ocupación), capital social (acompañamiento) y capital funcional (independencia funcional). La vulnerabilidad fue mayor en los residentes de Pasto. Los factores asociados con la vulnerabilidad fueron la ciudad de residencia, el sexo, el nivel educativo y el rol en el hogar.Conclusión. En el 58,55 % de las personas mayores, la vulnerabilidad se explicó por el uso del tiempo, la independencia funcional y el bienestar subjetivo. Estos hallazgos aportan elementos para el mejoramiento de la calidad de vida, principalmente en cuanto a la capacidad funcional para mantener la independencia, estar ocupados y fortalecer la salud mental.

Psychometric properties of the Vulnerability to Abuse Screening Scale for screening abuse of older adults.

PubMed

Dantas, Raquel Batista; Oliveira, Graziella Lage; Silveira, Andréa Maria

2017-04-10

Adapt and evaluate the psychometric properties of the Vulnerability to Abuse Screening Scale to identify risk of domestic violence against older adults in Brazil. The instrument was adapted and validated in a sample of 151 older adults from a geriatric reference center in the municipality of Belo Horizonte, State of Minas Gerais, in 2014. We collected sociodemographic, clinical, and abuse-related information, and verified reliability by reproducibility in a sample of 55 older people, who underwent re-testing of the instrument seven days after the first application. Descriptive and comparative analyses were performed for all variables, with a significance level of 5%. The construct validity was analyzed by the principal components method with a tetrachoric correlation matrix, the reliability of the scale by the weighted Kappa (Kp) statistic, and the internal consistency by the Kuder-Richardson estimator formula 20 (KR-20). The average age of the participants was 72.1 years (DP = 6.96; 95%CI 70.94-73.17), with a maximum of 92 years, and they were predominantly female (76.2%; 95%CI 69.82-83.03). When analyzing the relationship between the scores of the Vulnerability to Abuse Screening Scale, categorized by presence (score > 3) or absence (score < 3) of vulnerability to abuse, with clinical and health conditions, we found statistically significant differences for self-perception of health (p = 0.002), depressive symptoms (p = 0.000), and presence of rheumatism (p = 0.003). There were no statistically significant differences between sexes. The Vulnerability to Abuse Screening Scale acceptably evaluated validity in the transcultural adaptation process, demonstrating dimensionality coherent with the original proposal (four factors). In the internal consistency analysis, the instrument presented good results (KR-20 = 0.69) and the reliability via reproducibility was considered excellent for the global scale (Kp = 0.92). The Vulnerability to Abuse Screening Scale proved to be a valid instrument with good psychometric capacity for screening domestic abuse against older adults in Brazil. Adaptar e avaliar as propriedades psicométricas da Escala Triagem de Vulnerabilidade ao Abuso (Vulnerability to Abuse Screening Scale - VASS) para identificar risco de violência doméstica contra idosos no Brasil. O instrumento foi adaptado e validado em uma amostra de 151 idosos de um centro de referência do idoso, do município de Belo Horizonte, MG, em 2014. Foram coletadas informações sociodemográficas, clínicas e relacionadas a abusos. A confiabilidade via reprodutibilidade foi verificada em uma amostra de 55 idosos, submetidos ao reteste do instrumento sete dias após a primeira aplicação. Foram realizadas análises descritivas e comparativas para todas as variáveis, com nível de significância de 5%. A validade de construto foi analisada pelo método de componentes principais com matriz de correlação tetracórica, a confiabilidade da escala pela estatística Kappa ponderado (Kp) e a consistência interna pelo estimador Kuder-Richardson fórmula 20 (KR-20). A idade média dos participantes foi 72,1 anos (DP = 6,96; IC95% 70,94-73,17), com máxima de 92 anos, e o sexo foi predominantemente feminino (76,2%; IC95% 69,82-83,03). Ao analisar a relação entre os escores da Escala Triagem de Vulnerabilidade ao Abuso, categorizados em presença (índice > 3) ou ausência (índice < 3) de vulnerabilidade para abuso, com condições clínicas e de saúde, encontramos diferenças estatisticamente significantes para autopercepção de saúde (p = 0,002), sintomas depressivos (p = 0,000) e presença de reumatismo (p = 0,003). Em relação ao sexo, não houve diferença estatisticamente significante. A Escala Triagem de Vulnerabilidade ao Abuso comportou-se de forma aceitável na avaliação da validade no processo de adaptação transcultural, demonstrando dimensionalidade coerente com a proposta original (quatro fatores). Na análise da consistência interna, o instrumento apresentou bons resultados (KR-20 = 0,69) e a confiabilidade via reprodutibilidade foi considerara excelente para a escala global (Kp = 0,92). A Escala Triagem de Vulnerabilidade ao Abuso mostra-se como instrumento válido e com boas capacidades psicométricas para o rastreio de abuso doméstico contra idosos no contexto brasileiro.

76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.

Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine transients in the dorsomedial and dorsolateral striatum.

PubMed

Robinson, John D; Howard, Christopher D; Pastuzyn, Elissa D; Byers, Diane L; Keefe, Kristen A; Garris, Paul A

2014-08-01

Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by means of autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity.

Striatal dopamine neurotransmission: regulation of release and uptake

PubMed Central

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

2016-01-01

Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients. PMID:27141430

Conacyt

Science.gov Websites

Organismos de Inspección Organismos de Certificación de personas Calidad Acreditación ¿Que es la : Estructuración de la Evaluación de la Conformidad 1.2: Fortalecimiento y articulación de las instituciones Componente 2: Fortalecimiento del Sistema Nacional de Innovación 6: Incorporación de la Innovación en la

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

77 FR 54800 - Airworthiness Directives; Diamond Aircraft Industries GmbH Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... airworthiness directive (AD) for certain Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG... products. The MCAI states: During conversion of a DA 42 to a DA 42 NG, voids were detected in the adhesive... the following Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG airplanes...

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS PHARMACOLOGICALLY EVOKED DOPAMINE TRANSIENTS IN THE DORSOMEDIAL AND DORSOLATERAL STRIATUM

PubMed Central

Robinson, John D.; Howard, Christopher D.; Pastuzyn, Elissa D.; Byers, Diane L.; Keefe, Kristen A.; Garris, Paul A.

2014-01-01

Phasic dopamine (DA) signaling, during which burst firing by dopamine neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity. PMID:24562969

Analysis of protein profiles in diabetic rat blood plasma that induced by alloxan

NASA Astrophysics Data System (ADS)

Hidayati, Dewi; Abdulgani, Nurlita; Setiyawan, Hengki; Trisnawati, Indah; Ashuri, Nova Maulidina; Sa'adah, Noor Nailis

2017-06-01

Proteomics is the study to identify the proteins involved in physiological metabolic pathway. The protein profiles of blood plasma from alloxan-induced diabetic rats has investigated using Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Data were analyzed descriptively based on variations of the type and intensity of the protein. There were identified the similarity of protein variant between diabetic and control rats included ankyrin (200kDa), IgG (150kDa), nephrin (136 kDa), IDE (112 kDA), albumin (66 kDa), prealbumin (55 kDA), CICP (43 kDa), ApoA-V (39 kDa), GAPDH (35 kDa), C-RP (27,1 kDa), leptin (16 kDa) and apelin (13 kDa). However, the apelin profile at diabetic rats shows the higher intensity than control.

PROPOSAL OF A REVISIONAL SURGERY TO TREAT SEVERE NUTRITIONAL DEFICIENCY POST-GASTRIC BYPASS.

PubMed

Sampaio-Neto, José; Branco-Filho, Alcides José; Nassif, Luis Sérgio; Nassif, André Thá; Masi, Flávia David João De; Gasperin, Graciany

The gastric bypass has nutritional and electrolyte disturbances rate of approximately 17%. The most common deficits are protein malnutrition, ferric and zinc, in addition to the vitamin. Although rare, some malnutrition stages reach such severity that ends up being necessary hospitalization and sometimes revisional or reversal surgical procedures. To present a proposal of surgical revision for treatment of severe malnutrition after bariatric surgery. The procedure is to reconstitute the food transit through the duodenum and proximal jejunum, keeping the gastric bypass restrictive component. As an additional strategy, the gastric fundus resection is performed, aiming to intensify the suppression of the greline and avoiding excessive weight regain. After initial stabilization, nutritional and electrolytic support, the procedure was performed in two patients as definitive treatment of malnutrition status. Good results were observed at one year follow up. As improvement option and/or resolution of the nutritional alterations, surgical therapy is one of the alternatives. There is still no consensus on the surgical technique to be performed. This procedure is based on pathophysiological factors for the treatment of this condition, with good initial results, without significant clinical alterations. Longer follow-up will determine its effectiveness. O bypass gástrico consta com taxa de distúrbios nutricionais e eletrolíticos de aproximadamente 17%. Os déficits mais frequentes são a desnutrição proteica, férrica e de zinco, além das vitamínicas. Apesar de raros, alguns quadros de desnutrição atingem tal gravidade que acaba sendo indicada internação e, por vezes, procedimentos cirúrgicos revisionais ou de reversão. Apresentar proposta de cirurgia revisional para tratamento de desnutrição severa após bypass gástrico. O procedimento consiste em reconstituir o trânsito alimentar pelo duodeno e jejuno proximal, mantendo o componente restritivo do bypass gástrico. Como estratégia adicional, é realizada ressecção do fundo gástrico, visando intensificar a supressão da grelina e evitando reganho excessivo de peso. Após estabilização inicial com suporte hidroeletrlítico e nutricional, o procedimento foi realizado em dois pacientes como tratamento definitivo do quadro de desnutrição. Bons resultados foram observados em seguimento de um ano. Como opção de melhora e/ou resolução da defasagem nutricional, a terapia cirúrgica é uma das alternativas. Ainda não há consenso quanto à técnica a ser utilizada. O procedimento aqui apresentado é baseado em fatores fisiopatológicos para o tratamento desta condição, com bons resultados iniciais, sem efeitos colaterais significativos. Seguimento de mais longo prazo é necessário para determinação de sua eficácia.

Imaging Magnetic Vortices Dynamics Using Lorentz Electron Microscopy with GHz Excitations

NASA Astrophysics Data System (ADS)

Zhu, Yimei

2015-03-01

Magnetic vortices in thin films are naturally formed spiral spin configurations with a core polarization pointing out of the film plane. They typically represent ground states with high structural and thermal stability as well as four different chirality-polarity combinations, offering great promise in the development of spin-based devices. For applications to spin oscillators, non-volatile memory and logic devices, the fundamental understanding and precise control of vortex excitations and dynamic switching behavior are essential. The compact dimensionality and fast spin dynamics set grand challenges for direct imaging technologies. Recently, we have developed a unique method to directly visualize the dynamic magnetic vortex motion using advanced Lorentz electron microscopy combined with GHz electronic excitations. It enables us to map the orbit of a magnetic vortex core in a permalloy square with <5nm resolution and to reveal subtle changes of the gyrotropic motion as the vortex is driven through resonance. Further, in multilayer spin-valve disks, we probed the strongly coupled coaxial vortex motion in the dipolar- and indirect exchange-coupled regimes and unraveled the underlying coherence and modality. Our approach is complementary to X-ray magnetic circular dichroism and is of general interest to the magnetism community as it paves a way to study fundamental spin phenomena with unprecedented resolution and accuracy. Collaborations with S.D. Pollard, J.F. Pulecio, D.A. Arena and K.S. Buchanan are acknowledged. Work supported by DOE-BES, Material Sciences and Engineering Division, under Contract No. DE-AC02-98CH10886.

Financing of Pharmaceutical Services in the municipal management of the Brazilian Unified Health System

PubMed Central

Faleiros, Daniel Resende; Acurcio, Francisco de Assis; Álvares, Juliana; do Nascimento, Renata Cristina Rezende Macedo; Costa, Ediná Alves; Guibu, Ione Aquemi; Soeiro, Orlando Mario; Leite, Silvana Nair; Karnikowski, Margô Gomes de Oliveira; Costa, Karen Sarmento; Guerra, Augusto Afonso

2017-01-01

ABSTRACT OBJECTIVE To discuss factors related to the financing of the Basic Component of Pharmaceutical Services within the municipal management of the Brazilian Unified Health System. METHODS The Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil – Serviços (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines – Services) is a cross-sectional, exploratory, and evaluative study that performed an information survey in a representative sample, stratified by Brazilian regions It considered different study populations in the sampling plan, which represent primary health care services in the cities. Data were collected in 2015 by two methods: in person, by applying direct observation scripts and interviews with users, physicians, and professionals responsible for the dispensing of medicines in primary care services; by telephone interviews with municipal health managers and municipal professionals responsible for Pharmaceutical Services. The results were extracted from the questionnaires applied by telephone. RESULTS Of the sample of 600 eligible cities, we collected 369 interviews (61.5%) with secretaries and 507 (84.5%) with pharmaceutical services managers. 70.8% of the cities have a computerized management system; and 11.9% have qualification/training of professionals. More than half (51.3%) of the cities received funds for the structuring of pharmaceutical services, and almost 60% of these cities performed this type of spending. In 35.4% of cases, municipal secretaries of health said that they use resources of medicines from the Componente Básico da Assistência Farmacêutica (CBAF – Basic Component of Pharmaceutical Services) to cover demands of other medicines, but only 9.7% believed that these funds were sufficient to cover the demands. The existence of a permanent bidding committee exclusively for acquiring medicines was reported in 40.0% of the cities. CONCLUSIONS We found serious deficiencies in the public financing of medicines, as well as little concern about the formality in the use of public resources, expenses that meet individual demands to the detriment of the community, insufficient resources allocated to the Basic Component of Pharmaceutical Services, and exhaustion of the financing model. PMID:29160447

Financing of Pharmaceutical Services in the municipal management of the Brazilian Unified Health System.

PubMed

Faleiros, Daniel Resende; Acurcio, Francisco de Assis; Álvares, Juliana; Nascimento, Renata Cristina Rezende Macedo do; Costa, Ediná Alves; Guibu, Ione Aquemi; Soeiro, Orlando Mario; Leite, Silvana Nair; Karnikowski, Margô Gomes de Oliveira; Costa, Karen Sarmento; Guerra, Augusto Afonso

2017-11-13

To discuss factors related to the financing of the Basic Component of Pharmaceutical Services within the municipal management of the Brazilian Unified Health System. The Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil - Serviços (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines - Services) is a cross-sectional, exploratory, and evaluative study that performed an information survey in a representative sample, stratified by Brazilian regions It considered different study populations in the sampling plan, which represent primary health care services in the cities. Data were collected in 2015 by two methods: in person, by applying direct observation scripts and interviews with users, physicians, and professionals responsible for the dispensing of medicines in primary care services; by telephone interviews with municipal health managers and municipal professionals responsible for Pharmaceutical Services. The results were extracted from the questionnaires applied by telephone. Of the sample of 600 eligible cities, we collected 369 interviews (61.5%) with secretaries and 507 (84.5%) with pharmaceutical services managers. 70.8% of the cities have a computerized management system; and 11.9% have qualification/training of professionals. More than half (51.3%) of the cities received funds for the structuring of pharmaceutical services, and almost 60% of these cities performed this type of spending. In 35.4% of cases, municipal secretaries of health said that they use resources of medicines from the Componente Básico da Assistência Farmacêutica (CBAF - Basic Component of Pharmaceutical Services) to cover demands of other medicines, but only 9.7% believed that these funds were sufficient to cover the demands. The existence of a permanent bidding committee exclusively for acquiring medicines was reported in 40.0% of the cities. We found serious deficiencies in the public financing of medicines, as well as little concern about the formality in the use of public resources, expenses that meet individual demands to the detriment of the community, insufficient resources allocated to the Basic Component of Pharmaceutical Services, and exhaustion of the financing model.

New tools for subsurface imaging of 3D seismic Node data in hydrocarbon exploration =

NASA Astrophysics Data System (ADS)

Benazzouz, Omar

A aquisicao de dados sismicos de reflexao multicanal 3D/4D usando Ocean Bottom NODES de 4 componentes constitui atualmente um sector de importancia crescente no mercado da aquisicao de dados reflexao sismica marinha na industria petrolifera. Este tipo de dados permite obter imagens de sub-superficie de alta qualidade, com baixos niveis de ruido, banda larga, boa iluminacao azimutal, offsets longos, elevada resolucao e aquisicao de tanto ondas P como S. A aquisicao de dados e altamente repetitiva e portanto ideal para campanhas 4D. No entanto, existem diferencas significativas na geometria de aquisicao e amostragem do campo de ondas relativamente aos metodos convencionais com streamers rebocados a superficie, pelo que e necessario desenvolver de novas ferramentas para o processamento deste tipo de dados. Esta tese investiga tres aspectos do processamento de dados de OBSs/NODES ainda nao totalmente resolvidos de forma satisfatoria: a deriva aleatoria dos relogios internos, o posicionamento de precisao dos OBSs e a implementacao de algoritmos de migracao prestack 3D em profundidade eficientes para obtencao de imagens precisas de subsuperficie. Foram desenvolvidos novos procedimentos para resolver estas situacoes, que foram aplicados a dados sinteticos e a dados reais. Foi desenvolvido um novo metodo para deteccao e correccao de deriva aleatoria dos relogios internos, usando derivadas de ordem elevada. Foi ainda desenvolvido um novo metodo de posicionamento de precisao de OBSs usando multilateracao e foram criadas ferramentas de interpolacao/extrapolacao dos modelos de velocidades 3D de forma a cobrirem a extensao total area de aquisicao. Foram implementados algoritmos robustos de filtragem para preparar o campo de velocidades para o tracado de raios e minimizar os artefactos na migracao Krichhoff pre-stack 3D em profundidade. Os resultados obtidos mostram um melhoramento significativo em todas as situacoes analisadas. Foi desenvolvido o software necessario para o efeito e criadas solucoes computacionais eficientes. As solucoes computacionais desenvolvidas foram integradas num software standard de processamento de sismica (SPW) utilizado na industria, de forma a criar, conjuntamente com as ferramentas ja existentes, um workflow de processamento integrado para dados de OBS/NODES, desde a aquisicao e controle de qualidade a producao dos volumes sismicos migrados pre-stack em profundidade.

Analysis of the mechanisms by which amphetamine releases dopamine from striatal dopaminergic neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.M.

1987-01-01

The goals of the studies were (1) to determine the intraneuronal transmitter pools that contribute to the efflux of dopamine (DA) elicited by amphetamine (AMPH) and (2) to determine the biochemical mechanism by which AMPH increases DA efflux from dopaminergic neurons. AMPH increased the efflux of endogenous DA and decreased the electrically-evoked overflow of (/sup 3/H) acetylcholine (ACh) from superfused rabbit striatal slices. These effects were most pronounced when both vesicular DA stores and DA synthesis were intact. Therefore, extravesicular, newly synthesized DA and vesicular stores of DA contribute to AMPH-induced DA efflux. Simultaneous inhibition of monoamine oxidase (MAO) andmore » neuronal DA uptake did not increase the efflux of endogenous DA or inhibit the electrically-evoked overflow of (/sup 3/H)ACh to the same extent as AMPH. Hence, inhibition of MAO and neuronal DA uptake are probably not the major mechanisms by which AMPH increases DA efflux. The AMPH-induced efflux of endogenous or (/sup 3/H)DA was blocked by inhibitors of neuronal DA uptake.« less

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Method for Impeding Degradation of Porous Silicon Structures

NASA Technical Reports Server (NTRS)

Vilentchouk, Biana Godin; Ferrari, Mauro

2011-01-01

This invention relates to surface modification of porosified silicon (pSi) structures with poly(alkylene) glycols for the purpose of controlled degradation of the silicon matrix and tailored release of encapsulated substances for biomedical applications. The pSi structures are currently used in diverse biomedical applications including bio-molecular screening, optical bio-sensoring, and drug delivery by means of injectable/orally administered carriers and implantable devices. The size of the pores and the surface chemistry of the pSi structure can be controlled during the microfabrication process and thereafter. A fine regulation of the degradation kinetics of mesoporous silicon structures is of fundamental importance. Polyethylene glycols (PEGs) represent the major category of surface modifying agents used in classical drug delivery systems and in pharmaceutical dosage forms. PEGylation enables avoidance of RES uptake, thus prolonging circulation time of intravenously injectable nanovectors. PEG molecules demonstrate little toxicity and immunogenicity, and are cleared from the body through the urine (molecular weight, MW less than 30 kDa) or in the feces (MW greater than 30kDa). The invention focuses on the possibility of finely tuning the degradation kinetics of the pSi nanovectors and other structures through surface conjugation of PEGs with various backbone lengths/MWs. To prove the concept, pSi nanovectors were covalently conjugated to seven PEGs with MW from 245 to 5,000 Da and their degradation kinetics in physiologically relevant media (phosphate buffer saline, PBS pH7.4, and fetal bovine serum) was assessed by the elemental analysis of the Si using inductive coupled plasma atomic emission spectroscopy (ICP-AES). The conjugation of the PEG with lowest MW to the nanovectors surface did not induce any change in the degradation kinetics in serum, but inhibited degradation and consequently the release of orthosilicic acid into buffer. When PEGs with the longer chains were evaluated, Si mass loss from the nanovectors was slowed down, and the PEGylated structures were almost fully degraded within 18 24 hours in serum and within 48 hours in PBS. The most dramatic effect was observed for high MW PEGs 3,400 and 5,000 Da, which prominently inhibited the degradation of the systems, with complete degradation achieved only after four days. For these PEGs, during the early stages of the degradation, there was a lag period of little or no Si mass loss from the nanovector. The obtained profiles were in agreement with the erosion of the nanovector surface as observed by scanning electron microscopy.

Estimated costs of advanced lung cancer care in a public reference hospital.

PubMed

Knust, Renata Erthal; Portela, Margareth Crisóstomo; Pereira, Claudia Cristina de Aguiar; Fortes, Guilherme Bastos

2017-08-17

To estimate the direct medical costs of advanced non-small cell lung cancer care. We assessed a cohort of 277 patients treated in the Brazilian National Cancer Institute in 2011. The costs were estimated from the perspective of the hospital as a service provider of reference for the Brazilian Unified Health System. The materials and procedures used were identified and quantified, per patient, and we assigned to them monetary values, consolidated in phases of the assistance defined. The analyses had a descriptive character with costs in Real (R$). Overall, the cohort represented a cost of R$2,473,559.91, being 71.5% related to outpatient care and 28.5% to hospitalizations. In the outpatient care, costs with radiotherapy (34%) and chemotherapy (22%) predominated. The results pointed to lower costs in the initial phase of treatment (7.2%) and very high costs in the maintenance phase (61.6%). Finally, we identified statistically significant differences of average cost by age groups, education levels, physical performance, and histological type. This study provides a current, useful, and relevant picture of the costs of patients with non-small cell lung cancer treated in a public hospital of reference and it provides information on the magnitude of the problem of cancer in the context of public health. The results confirm the importance of radiation treatment and hospitalizations as the main components of the cost of treatment. Despite some losses of follow-up, we assess that, for approximately 80% of the patients included in the study, the estimates presented herein are satisfactory for the care of the disease, from the perspective of a service provider of reference of the Brazilian Unified Health System, as it provides elements for the management of the service, as well as for studies that result in more rational forms of resource allocation. Estimar os custos médicos diretos da assistência ao câncer de pulmão não pequenas células avançado. Foi avaliada uma coorte de 277 pacientes matriculados no Instituto Nacional do Câncer em 2011. Os custos foram estimados sob a perspectiva do hospital como prestador de serviços de referência para o SUS. Insumos e procedimentos utilizados foram identificados e quantificados, por paciente, sendo a eles atribuídos valores monetários, consolidados por fases da assistência definidas. As análises tiveram caráter descritivo com custos em reais (R$). Em termos globais, a coorte representou um custo de R$2.473.559,91, sendo 71,5% relacionados à atenção ambulatorial e 28,5% as internações. Na atenção ambulatorial, predominaram os custos com radioterapia (34%) e quimioterapia (22%). Os resultados apontaram para custos menores na fase inicial de tratamento (7,2%) e custos muito elevados na fase de manutenção (61,6%). Por fim, identificaram-se diferenças estatisticamente significativas das médias dos custos por faixas etárias, níveis de escolaridade, desempenho físico e tipo histológico. Este estudo fornece um retrato atual, útil e relevante sobre os custos de pacientes com câncer de pulmão não pequenas células assistidos em um hospital público de referência e provê elementos sobre a magnitude do problema do câncer no âmbito da saúde pública. Os resultados ratificam a importância do tratamento radioterápico e das internações como principais componentes de custo do tratamento. Apesar de algumas perdas de seguimento avalia-se que, para cerca de 80% dos pacientes incluídos no estudo, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS, fornecendo elementos para a gestão do serviço, bem como para estudos que redundem em formas mais racionais de alocação de recursos.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS NATURALLY OCCURRING PHASIC DOPAMINE SIGNALING

PubMed Central

Howard, Christopher D.; Daberkow, David P.; Ramsson, Eric S.; Keefe, Kristen A.; Garris, Paul A.

2013-01-01

Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems. Although striatal DA depletions induced by METH are associated with behavioral and cognitive impairments, the link between these phenomena remains poorly understood. Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, prior studies used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called “spontaneous” phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these sub-second DA changes may play a role in enhancing reward-cue associations. METH-pretreatment reduced tissue DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients and are consistent with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. PMID:23574406

Somatodendritic dopamine release: recent mechanistic insights

PubMed Central

Rice, Margaret E.; Patel, Jyoti C.

2015-01-01

Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding.

PubMed

Basagiannis, Dimitris; Christoforidis, Savvas

2016-08-05

VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Molecular cloning, expression and characterization of lysine decarboxylase gene of endophytic fungus Shiraia sp. Slf14 from Huperzia serrata].

PubMed

Peng, Silu; Yang, Huilin; Zhu, Du; Zhang, Zhibin; Yan, Riming; Wang, Ya

2016-04-14

Huperzine A (HupA) was approved as a drug for the treatment of Alzheimer's disease. The HupA biosynthetic pathway was started from lysine decarboxylase (LDC), which catalyzes lysine to cadaverine. In this study, we cloned and expressed an LDC gene from a HupA-producing endophytic fungus, and tested LDC activities. An endophytic fungus Shiraia sp. Slf14 from Huperzia serrata was used. LDC gene was obtained by RT-PCR, and cloned into pET-22b(+) and pET-32a(+) vectors to construct recombinant plasmids pET- 22b-LDC and pET-32a-LDC. These two recombinant plasmids were transformed into E. coli BL21, cultured for 8 h at 24 °C, 200 r/min with 1×10–3 mol/L IPTG into medium to express the LDC proteins, respectively. LDC proteins were purified by Ni2+ affinity chromatography. Catalytic activities were measured by Thin Layer Chromatography. At last, the physicochemical properties and structures of these two LDCs were obtained by bioinformatics software. LDC and Trx-LDC were expressed in E. coli BL21 successfully. SDS-PAGE analysis shows that the molecular weight of LDC and Trx-LDC were 24.4 kDa and 42.7 kDa respectively, which are consistent with bioinformatics analysis. In addition, TLC analysis reveals that both LDC and Trx-LDC had catalytic abilities. This work can provide fundamental data for enriching LDC molecular information and reveal the HupA biosynthetic pathway in endophytic fungi.

Evolution of superconducting gap and metallic ground state in cuprates from transport

NASA Astrophysics Data System (ADS)

Taillefer, Louis

2006-03-01

We report on fundamental characteristics of the ground state of cuprates in the limit of T=0, for both normal and superconducting states, obtained from transport measurements on high-quality single crystals of YBCO and Tl-2201, as a function of hole concentration. The superconducting gap is extracted from thermal conductivity; it is found to scale with the superconducting transition temperature throughout the overdoped regime, with a gap-to-Tc ratio of 5 [1]. The normal state is accessed by suppressing superconductivity with magnetic fields up to 60 T and is characterized by the limiting behavior of its electrical resistivity; while carrier localization is observed in YBCO at low temperature for carrier concentrations p below 0.1 hole/planar Cu, at p=0.1 and above the material remains highly metallic down to T=0 [2]. This shows that the non-superconducting state of underdoped cuprates, deep in the pseudogap phase, is remarkably similar to that of strongly overdoped cuprates, e.g. at p=0.3. We compare these results with similar measurements on other cuprates and discuss their implication for our understanding of the cuprate phase diagram. [1] In collaboration with: D.G. Hawthorn, S.Y. Li, M. Sutherland, E. Boaknin, R.W. Hill, C. Proust, F. Ronning, M. Tanatar, J. Paglione, D. Peets, R. Liang, D.A. Bonn, W.N. Hardy, and N.N. Kolesnikov. [2] In collaboration with: C. Proust, M. Sutherland, N. Doiron- Leyraud, S.Y. Li, R. Liang, D.A. Bonn, W.N. Hardy, N.E. Hussey, S. Adachi, S. Tajima, J. Levallois, and M. Narbone.

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding*

PubMed Central

Basagiannis, Dimitris; Christoforidis, Savvas

2016-01-01

VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors. PMID:27298320

Dopamine D2 receptor over-expression alters behavior and physiology in Drd2-EGFP mice

PubMed Central

Kramer, Paul F.; Christensen, Christine H.; Hazelwood, Lisa A.; Dobi, Alice; Bock, Roland; Sibley, David R.; Mateo, Yolanda; Alvarez, Veronica A.

2011-01-01

BAC transgenic mice expressing the fluorescent reporter protein EGFP under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological function of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display a ~40% increase in membrane expression of the dopamine D2 receptor (D2R) and a two-fold increase in D2R mRNA levels in the striatum when compared to wild-type and Drd1-EGFP mice D2R over-expression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. DA transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice over-express D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice. PMID:21209197

Biomechanics of the press-fit phenomenon in dental implantology: an image-based finite element analysis.

PubMed

Frisardi, Gianni; Barone, Sandro; Razionale, Armando V; Paoli, Alessandro; Frisardi, Flavio; Tullio, Antonio; Lumbau, Aurea; Chessa, Giacomo

2012-05-29

A fundamental pre-requisite for the clinical success in dental implant surgery is the fast and stable implant osseointegration. The press-fit phenomenon occurring at implant insertion induces biomechanical effects in the bone tissues, which ensure implant primary stability. In the field of dental surgery, the understanding of the key factors governing the osseointegration process still remains of utmost importance. A thorough analysis of the biomechanics of dental implantology requires a detailed knowledge of bone mechanical properties as well as an accurate definition of the jaw bone geometry. In this work, a CT image-based approach, combined with the Finite Element Method (FEM), has been used to investigate the effect of the drill size on the biomechanics of the dental implant technique. A very accurate model of the human mandible bone segment has been created by processing high resolution micro-CT image data. The press-fit phenomenon has been simulated by FE analyses for different common drill diameters (DA=2.8 mm, DB=3.3 mm, and DC=3.8 mm) with depth L=12 mm. A virtual implant model has been assumed with a cylindrical geometry having height L=11 mm and diameter D=4 mm. The maximum stresses calculated for drill diameters DA, DB and DC have been 12.31 GPa, 7.74 GPa and 4.52 GPa, respectively. High strain values have been measured in the cortical area for the models of diameters DA and DB, while a uniform distribution has been observed for the model of diameter DC . The maximum logarithmic strains, calculated in nonlinear analyses, have been ϵ=2.46, 0.51 and 0.49 for the three models, respectively. This study introduces a very powerful, accurate and non-destructive methodology for investigating the effect of the drill size on the biomechanics of the dental implant technique.Further studies could aim at understanding how different drill shapes can determine the optimal press-fit condition with an equally distributed preload on both the cortical and trabecular structure around the implant.

Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in-vivo microdialysis data.

PubMed

Kim, Sang Eun; Han, Seung-Moo

2009-07-01

The effect of substances which alter extracellular dopamine (DA) concentration has been studied by measuring changes in the binding of radiolabelled raclopride, a DA D2 receptor ligand that is sensitive to endogenous DA. To better characterize the relationship between extracellular DA concentration and DA D2 receptor binding of raclopride, we compared the changes of extracellular DA concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride binding induced by different doses of methamphetamine (Meth) and nicotine, drugs that enhance DA release with and without blocking DA transporters (DATs), respectively, in rat striatum. Nicotine elicited a modest increase of striatal extrasynaptic extracellular DA, while Meth produced a marked increase of striatal extrasynaptic DA in a dose-dependent manner. There was a close correlation between the decrease in [3H]raclopride in-vivo binding and the increase in extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled raclopride-binding measurement for the non-invasive assessment of DA release following interventions in the living brain. However, the linear regression analysis revealed that the ratio of percent DA increase to percent [3H]raclopride binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1). The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding relationship between the DA-enhancing drugs with and without DAT-blocking property indicates that the competition between endogenous DA and radiolabelled raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2 receptors and reflects synaptic concentration of DA.

Cyclopentadithiophene-Benzothiadiazole Donor-Acceptor Polymers as Prototypical Semiconductors for High-Performance Field-Effect Transistors.

PubMed

Li, Mengmeng; An, Cunbin; Pisula, Wojciech; Müllen, Klaus

2018-05-15

Donor-acceptor (D-A) conjugated polymers are of great interest as organic semiconductors, because they offer a rational tailoring of the electronic properties by modification of the donor and acceptor units. Nowadays, D-A polymers exhibit field-effect mobilities on the order of 10 -2 -10 0 cm 2 V -1 s -1 , while several examples showed a mobility over 10 cm 2 V -1 s -1 . The development of cyclopentadithiophene-benzothiadiazole (CDT-BTZ) copolymers one decade ago represents an important step toward high-performance organic semiconductors for field-effect transistors. The significant rise in field-effect mobility of CDT-BTZ in comparison to the existing D-A polymers at that time opened the door to a new research field with a large number of novel D-A systems. From this point, the device performance of CDT-BTZ was gradually improved by a systematic optimization of the synthesis and polymer structure as well as by an efficient solution processing into long-range ordered thin films. The key aspect was a comprehensive understanding of the relation between polymer structure and solid-state organization. Due to their fundamental role for the field of D-A polymers in general, this Account will for the first time explicitly focus on prototypical CDT-BTZ polymers, while other reviews provide an excellent general overview on D-A polymers. The first part of this Account discusses strategies for improving the charge carrier transport, focusing on chemical aspects. Improved synthesis as an essential stage toward high purity, and high molecular weight is a prerequisite for molecular order. The modification of substituents is a further crucial feature to tune the CDT-BTZ packing and self-assembly. Linear alkyl side chains facilitate intermolecular π-stacking interactions, while branched ones increase solubility and alter the polymer packing. Additional control over the supramolecular organization of CDT-BTZ polymers is introduced by alkenyl substituents via their cis-trans isomerization. The last discussed chemical concept is based on heteroatom variation within the CDT unit. The relationships found experimentally for CDT-BTZ between polymer chemical structure, solid-state organization, and charge carrier transport are explained by means of theoretical simulations. Besides the effects of molecular design, the second part of this Account discusses the processing conditions from solution. The film microstructure, defined as a mesoscopic domain organization, is critically affected by solution processing. Suitable processing techniques allow the formation of a long-range order and a uniaxial orientation of the CDT-BTZ chains, thus lowering the trapping density of grain boundaries for charge carriers. For instance, alignment of the CDT-BTZ polymer by dip-coating yields films with a pronounced structural and electrical anisotropy and favors a fast migration of charge carriers along the conjugated backbones in the deposition direction. By using film compression with the assistance of an ionic liquid, one even obtains CDT-BTZ films with a band-like transport and a transistor hole mobility of 10 cm 2 V -1 s -1 . This device performance is attributed to large domains in the compressed films being formed by CDT-BTZ with longer alkyl chains, which establish a fine balance between polymer interactions and growth kinetics during solvent evaporation. On the basis of the prototypical semiconductor CDT-BTZ, this Account provides general guidelines for achieving high-performance polymer transistors by taking into account the subtle balance of synthetic protocol, molecular design, and processing.

Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson’s disease

PubMed Central

Zhang, Lifen; Le, Weidong; Xie, Wenjie; Dani, John A.

2011-01-01

The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knock-out (Nurr1 +/−) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/−) mice: 3–6, 9–12, and 15–23 months old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/− mice (3–6 months) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/− mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/− mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. PMID:21531044

Autocorrelation descriptor improvements for QSAR: 2DA_Sign and 3DA_Sign

NASA Astrophysics Data System (ADS)

Sliwoski, Gregory; Mendenhall, Jeffrey; Meiler, Jens

2016-03-01

Quantitative structure-activity relationship (QSAR) is a branch of computer aided drug discovery that relates chemical structures to biological activity. Two well established and related QSAR descriptors are two- and three-dimensional autocorrelation (2DA and 3DA). These descriptors encode the relative position of atoms or atom properties by calculating the separation between atom pairs in terms of number of bonds (2DA) or Euclidean distance (3DA). The sums of all values computed for a given small molecule are collected in a histogram. Atom properties can be added with a coefficient that is the product of atom properties for each pair. This procedure can lead to information loss when signed atom properties are considered such as partial charge. For example, the product of two positive charges is indistinguishable from the product of two equivalent negative charges. In this paper, we present variations of 2DA and 3DA called 2DA_Sign and 3DA_Sign that avoid information loss by splitting unique sign pairs into individual histograms. We evaluate these variations with models trained on nine datasets spanning a range of drug target classes. Both 2DA_Sign and 3DA_Sign significantly increase model performance across all datasets when compared with traditional 2DA and 3DA. Lastly, we find that limiting 3DA_Sign to maximum atom pair distances of 6 Å instead of 12 Å further increases model performance, suggesting that conformational flexibility may hinder performance with longer 3DA descriptors. Consistent with this finding, limiting the number of bonds in 2DA_Sign from 11 to 5 fails to improve performance.

Data Administration at a Regional University: A Case Study.

ERIC Educational Resources Information Center

Gose, Frank J.

Data administration (DA) is a position that has emerged with the growth of information technologies. A review of DA literature confirms that, although DA is widely associated with database management systems (DBMS), there is no standard DA job description, DA staffing and location within the organization vary, and DA functions range in description…

From sanddabs to blue whales: the pervasiveness of domoic acid.

PubMed

Lefebvre, Kathi A; Bargu, Sibel; Kieckhefer, Tom; Silver, Mary W

2002-07-01

Domoic acid (DA) is a potent food web transferred algal toxin that has caused dramatic mortality events involving sea birds and sea lions. Although no confirmed DA toxicity events have been reported in whales, here we present data demonstrating that humpback and blue whales are exposed to the toxin and consume DA contaminated prey. Whale fecal samples were found to contain DA at levels ranging from 10 to 207microg DA g(-1) feces via HPLC-UV methods. SEM analysis of whale feces containing DA, collected from krill-feeding whales, revealed the presence of diatom frustules identified as Pseudo-nitzschia australis, a known DA producer. Humpback whales were observed feeding on anchovies and sardines that contained DA at levels ranging from 75 to 444microg DA g(-1) viscera. DA contamination of whale feces and fish occurred only during blooms of toxic Pseudo-nitzschia. Additionally, several novel fish species collected during a toxic diatom bloom were tested for DA. Fish as diverse as benthic sanddabs and pelagic albacore were found to contain the neurotoxin, suggesting that DA permeates benthic as well as pelagic communities.

Two forms of Vibrio cholerae O1 El Tor hemolysin derived from identical precursor protein.

PubMed

Ikigai, H; Ono, T; Nakae, T; Otsuru, H; Shimamura, T

1999-01-08

Vibrio cholerae O1 grown in heart infusion broth produces two forms of El Tor hemolysin (ETH) monomers of 65 and 50 kDa. These monomers form several different sizes of mixed oligomers ranging from 180 to 280 kDa in the liposomal membranes. We found that the N-terminal amino acid sequences, NH2-Trp-Pro-Ala-Pro-Ala-Asn-Ser-Glu, of both the 65- and 50-kDa toxins were identical. We assumed, therefore, that the 65- and 50-kDa toxins were derivatives of the identical precursor protein and the 50-kDa protein was a truncated derivative of 65-kDa ETH. To substantiate this assumption, we treated the 260-kDa oligomer with trypsin and obtained a 190-kDa oligomer. This 190-kDa oligomer consisted of only the 50-kDa subunits. Both 260- and 190-kDa oligomers formed ion channels indistinguishable from each other in planar lipid bilayers. These results suggest that the essential part of the ETH in forming the membrane-damaging aggregate is a 50-kDa protein.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Platelets contribute to postnatal occlusion of the ductus arteriosus.

PubMed

Echtler, Katrin; Stark, Konstantin; Lorenz, Michael; Kerstan, Sandra; Walch, Axel; Jennen, Luise; Rudelius, Martina; Seidl, Stefan; Kremmer, Elisabeth; Emambokus, Nikla R; von Bruehl, Marie-Luise; Frampton, Jon; Isermann, Berend; Genzel-Boroviczény, Orsolya; Schreiber, Christian; Mehilli, Julinda; Kastrati, Adnan; Schwaiger, Markus; Shivdasani, Ramesh A; Massberg, Steffen

2010-01-01

The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

In-cell thermodynamics and a new role for protein surfaces.

PubMed

Smith, Austin E; Zhou, Larry Z; Gorensek, Annelise H; Senske, Michael; Pielak, Gary J

2016-02-16

There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge-charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.

Process and technoeconomic analysis of leading pretreatment technologies for lignocellulosic ethanol production using switchgrass.

PubMed

Tao, Ling; Aden, Andy; Elander, Richard T; Pallapolu, Venkata Ramesh; Lee, Y Y; Garlock, Rebecca J; Balan, Venkatesh; Dale, Bruce E; Kim, Youngmi; Mosier, Nathan S; Ladisch, Michael R; Falls, Matthew; Holtzapple, Mark T; Sierra, Rocio; Shi, Jian; Ebrik, Mirvat A; Redmond, Tim; Yang, Bin; Wyman, Charles E; Hames, Bonnie; Thomas, Steve; Warner, Ryan E

2011-12-01

Six biomass pretreatment processes to convert switchgrass to fermentable sugars and ultimately to cellulosic ethanol are compared on a consistent basis in this technoeconomic analysis. The six pretreatment processes are ammonia fiber expansion (AFEX), dilute acid (DA), lime, liquid hot water (LHW), soaking in aqueous ammonia (SAA), and sulfur dioxide-impregnated steam explosion (SO(2)). Each pretreatment process is modeled in the framework of an existing biochemical design model so that systematic variations of process-related changes are consistently captured. The pretreatment area process design and simulation are based on the research data generated within the Biomass Refining Consortium for Applied Fundamentals and Innovation (CAFI) 3 project. Overall ethanol production, total capital investment, and minimum ethanol selling price (MESP) are reported along with selected sensitivity analysis. The results show limited differentiation between the projected economic performances of the pretreatment options, except for processes that exhibit significantly lower monomer sugar and resulting ethanol yields. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis[C][W

PubMed Central

Xia, Tian; Li, Na; Dumenil, Jack; Li, Jie; Kamenski, Andrei; Bevan, Michael W.; Gao, Fan; Li, Yunhai

2013-01-01

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement. PMID:24045020

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.

PubMed

Lee, Joo H; Bae, Soo K; Kwon, Jong W; Kim, Won B; Lee, Myung G

2005-12-01

The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.

75 FR 75868 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal... of the Thielert Engine Owners Group commented that the Model DA 42 has the same door design and the same unsafe condition. He recommended that the AD also apply to the Model DA 42. The FAA has discussed...

Characterization of low molecular weight fragments from gamma irradiated κ-carrageenan used as plant growth promoter

NASA Astrophysics Data System (ADS)

Abad, Lucille V.; Aurigue, Fernando B.; Relleve, Lorna S.; Montefalcon, Djowel Recto V.; Lopez, Girlie Eunice P.

2016-01-01

Radiation degraded κ-carrageenan (1% solution at absorbed doses of 20 kGy and 30 kGy) were tested for its plant growth promoter (PGP) effect on pechay plants under hydroponics condition. Results revealed that higher PGP effects were found in κ-carrageenan irradiated at an absorbed dose of 30 kGy. Mw of irradiated κ-carrageenan as measured by GPC were determined to be 7362 Da and 6762 Da for 20 kGy and 30 kGy, respectively. Fractionation of the irradiated κ-carrageenan (30 kGy) was done to separate different Mw fractions using Mw cut-off filters of 1 kDa, 3 kDa, and 5 kDa. The PGP effect of the different retentates showed that biological activity in plants followed the order of 5 kDa>3 kDa>1 kDa using hydroponics condition but the reverse was observed in the order of 1 kDa>3 kDa>5 kDa when absorbed in plants by foliar spraying. GPC chromatogram indicated at least three (3) low molecular weight (LMW) fragments from radiation modified κ-carrageenan solution with an Mw<2000 Da. A fragment has also been identified with an Mw of as low as 160 Da which was produced under acidic (un-neutralized) condition. This may be attributed to the formation of 5-hydroxymethylfurfural (5-HMF).

The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

PubMed

Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

2008-06-23

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

PubMed Central

Bacci, B.; Cochran, E.; Nunzi, M. G.; Izeki, E.; Mizutani, T.; Patton, A.; Hite, S.; Sayre, L. M.; Autilio-Gambetti, L.; Gambetti, P.

1994-01-01

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7512790

Metaproteomics of Microbiota in Naturally Fermented Soybean Paste, Da-jiang.

PubMed

Zhang, Ping; Zhang, Pengfei; Xie, Mengxi; An, Feiyu; Qiu, Boshu; Wu, Rina

2018-05-01

Da-jiang is a typical traditional fermented soybean product in China. At present, the proteins in da-jiang are needed to be explored. The composition and species of microbial proteins in traditional fermented da-jiang were analyzed by metaproteomics based on sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that the number and variety of microbial proteins in the traditional fermented da-jiang from different regions were different. The production site influences the fermentation in da-jiang. Then we analyzed the functions of the microbial proteins identified in da-jiang, and found that they were mainly involved in the process of protein synthesis, glycometabolism and nucleic acid synthesis. In addtion, we compared the proteins composition in different da-jiang. There are 51 common proteins of naturally fermented da-jiang, and 25 common microbial sources. The main commonly microbial sources of fungal proteins are Saccharomyces cerevisiae and Schizosaccharomyces; the main commonly microbial sources of bacterial proteins are Enterococcus faecalis, Leuconostoc mesenteroides, Acinetobacter baumannii, and Bacillus subtilis. These common microbes play the predominant role in da-jiang fermentation. The present results help us to understand the fermentation of da-jiang and improve the quality and safety of final products in the future. The study illustrated metaproteome of microbiota in traditional fermented soybean paste, da-jiang, by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A method of extracting metaproteome from microbiota in da-jiang was attempted. The findings help to understand the fermentation of da-jiang and improve the quality and safety of da-jiang in fermented industry. © 2018 Institute of Food Technologists®.

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

PubMed Central

Steinkellner, Thomas; Farino, Zachary J.; Sonders, Mark S.; Villeneuve, Michael; Freyberg, Robin J.; Przedborski, Serge; Lu, Wei; Hnasko, Thomas S.

2018-01-01

Parkinson’s disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development. PMID:29337309

MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

PubMed

Weihmuller, F B; O'Dell, S J; Marshall, J F

1992-06-01

Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneities in Axonal Structure and Transporter Distribution Lower Dopamine Reuptake Efficiency

PubMed Central

Block, Ethan R.; Bartol, Tom M.; Sorkin, Alexander

2018-01-01

Abstract Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) substates were derived from molecular simulations. The complex morphology of axon terminals near active zones was observed to give rise to large variations in DA reuptake efficiency, and thereby in extracellular DA density. Comparison of the effect of different firing patterns showed that phasic firing would increase the probability of reaching local DA levels sufficiently high to activate low-affinity DA receptors, mainly owing to high DA levels transiently attained during the burst phase. The experimentally observed nonuniform surface distribution of DATs emerged as a major modulator of DA signaling: reuptake was slower, and the peaks/width of transient DA levels were sharper/wider under nonuniform distribution of DATs, compared with uniform. Overall, the study highlights the importance of accurate descriptions of extrasynaptic morphology, DAT distribution, and conformational kinetics for quantitative evaluation of dopaminergic transmission and for providing deeper understanding of the mechanisms that regulate DA transmission. PMID:29430519

Modafinil Activates Phasic Dopamine Signaling in Dorsal and Ventral Striata

PubMed Central

Bobak, Martin J.; Weber, Matthew W.; Doellman, Melissa A.; Schuweiler, Douglas R.; Athens, Jeana M.; Juliano, Steven A.

2016-01-01

Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders; however, its mechanism is not completely understood. Compared with other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling. This communication mode during which burst firing of DA neurons generates rapid changes in extracellular DA, the so-called DA transients, is critically implicated in reward learning. Here, we investigate MOD effects on phasic DA signaling in the striatum of urethane-anesthetized rats with fast-scan cyclic voltammetry. We found that MOD (30–300 mg/kg i.p.) robustly increases the amplitude of electrically evoked phasic-like DA signals in a time- and dose-dependent fashion, with greater effects in dorsal versus ventral striata. MOD-induced enhancement of these electrically evoked amplitudes was mediated preferentially by increased DA release compared with decreased DA uptake. Principal component regression of nonelectrically evoked recordings revealed negligible changes in basal DA with high-dose MOD (300 mg/kg i.p.). Finally, in the presence of the D2 DA antagonist, raclopride, low-dose MOD (30 mg/kg i.p.) robustly elicited DA transients in dorsal and ventral striata. Taken together, these results suggest that activation of phasic DA signaling is an important mechanism underlying the clinical efficacy of MOD. PMID:27733628

Genomic position affects the expression of tobacco mosaic virus movement and coat protein genes.

PubMed Central

Culver, J N; Lehto, K; Close, S M; Hilf, M E; Dawson, W O

1993-01-01

Alterations in the genomic position of the tobacco mosaic virus (TMV) genes encoding the 30-kDa cell-to-cell movement protein or the coat protein greatly affected their expression. Higher production of 30-kDa protein was correlated with increased proximity of the gene to the viral 3' terminus. A mutant placing the 30-kDa open reading frame 207 nucleotides nearer the 3' terminus produced at least 4 times the wild-type TMV 30-kDa protein level, while a mutant placing the 30-kDa open reading frame 470 nucleotides closer to the 3' terminus produced at least 8 times the wild-type TMV 30-kDa protein level. Increases in 30-kDa protein production were not correlated with the subgenomic mRNA promoter (SGP) controlling the 30-kDa gene, since mutants with either the native 30-kDa SGP or the coat protein SGP in front of the 30-kDa gene produced similar levels of 30-kDa protein. Lack of coat protein did not affect 30-kDa protein expression, since a mutant with the coat protein start codon removed did not produce increased amounts of 30-kDa protein. Effects of gene positioning on coat protein expression were examined by using a mutant containing two different tandemly positioned tobamovirus (TMV and Odontoglossum ringspot virus) coat protein genes. Only coat protein expressed from the gene positioned nearest the 3' viral terminus was detected. Analysis of 30-kDa and coat protein subgenomic mRNAs revealed no proportional increase in the levels of mRNA relative to the observed levels of 30-kDa and coat proteins. This suggests that a translational mechanism is primarily responsible for the observed effect of genomic position on expression of 30-kDa movement and coat protein genes. Images Fig. 2 Fig. 3 Fig. 4 PMID:8446627

Retention of fundamental surgical skills learned in robot-assisted surgery.

PubMed

Suh, Irene H; Mukherjee, Mukul; Shah, Bhavin C; Oleynikov, Dmitry; Siu, Ka-Chun

2012-12-01

Evaluation of the learning curve for robotic surgery has shown reduced errors and decreased task completion and training times compared with regular laparoscopic surgery. However, most training evaluations of robotic surgery have only addressed short-term retention after the completion of training. Our goal was to investigate the amount of surgical skills retained after 3 months of training with the da Vinci™ Surgical System. Seven medical students without any surgical experience were recruited. Participants were trained with a 4-day training program of robotic surgical skills and underwent a series of retention tests at 1 day, 1 week, 1 month, and 3 months post-training. Data analysis included time to task completion, speed, distance traveled, and movement curvature by the instrument tip. Performance of the participants was graded using the modified Objective Structured Assessment of Technical Skills (OSATS) for robotic surgery. Participants filled out a survey after each training session by answering a set of questions. Time to task completion and the movement curvature was decreased from pre- to post-training and the performance was retained at all the corresponding retention periods: 1 day, 1 week, 1 month, and 3 months. The modified OSATS showed improvement from pre-test to post-test and this improvement was maintained during all the retention periods. Participants increased in self-confidence and mastery in performing robotic surgical tasks after training. Our novel comprehensive training program improved robot-assisted surgical performance and learning. All trainees retained their fundamental surgical skills for 3 months after receiving the training program.

Central dopaminergic neurotransmission plays an important role in thermoregulation and performance during endurance exercise.

PubMed

Zheng, Xinyan; Hasegawa, Hiroshi

2016-10-01

Dopamine (DA) has been widely investigated for its potential role in determining exercise performance. It was originally thought that DA's ergogenic effect was by mediating psychological responses. Recently, some studies have also suggested that DA may regulate physiological responses, such as thermoregulation. Hyperthermia has been demonstrated as an important limiting factor during endurance exercise. DA is prominent in the thermoregulatory centre, and changes in DA concentration have been shown to affect core temperature regulation during exercise. Some studies have proposed that DA or DA/noradrenaline (NA) reuptake inhibitors can improve exercise performance, despite hyperthermia during exercise in the heat. DA/NA reuptake inhibitors also increase catecholamine release in the thermoregulatory centre. Intracerebroventricularly injected DA has been shown to improve exercise performance through inhibiting hyperthermia-induced fatigue, even at normal ambient temperatures. Further, caffeine has been reported to increase DA release in the thermoregulatory centre and improves endurance exercise performance despite increased core body temperature. Taken together, DA has been shown to have ergogenic effects and increase heat storage and hyperthermia tolerance. The mechanisms underlying these effects seem to involve limiting/overriding the inhibitory signals from the central nervous system that result in cessation of exercise due to hyperthermia.

Novel codrugs with GABAergic activity for dopamine delivery in the brain.

PubMed

Denora, Nunzio; Cassano, Tommaso; Laquintana, Valentino; Lopalco, Antonio; Trapani, Adriana; Cimmino, Concetta Stefania; Laconca, Leonardo; Giuffrida, Andrea; Trapani, Giuseppe

2012-11-01

This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

[CHARACTERISTICS OF COMBINED ANESTHESIA WITH EPIDURAL COMPONENTE DEPENDING ON VEGETATIVE NERVOUS SYSTEM TYPE].

PubMed

Hasanov, F J; Aslanov, A A; Muradov, N F; Namazova, K N

2016-01-01

The research objective was to study the characteristics of combined anesthesia with epidural componente (CAEC) depending on vegetative nervous system type (VNS) in patients who underwent large scale traumatic surgical operations on abdominal cavity organs. The scientific research was conducted in Anaesthesiology--Reanimation Department of the Scientific Surgical Centre named after acad. MA. Topchubashev, the Ministry of Health of the Azerbaijan Republic. The research objects were 69 patients who underwent operations in conditions of CAEC due to different serious surgical pathologies of abdominal cavity organs. VNS type was identified based on electroencephalogram, Cerdo Vegetative Index (CVI), Hildebrandt coefficient (HC) and single neurophysiological tests. The patients were divided into three groups depending on VNS type: I--normotonics--17 patients (24.7%), II--sympathatonics--25 patients (36.2%), and III--vagotonics--27 patients (39.1%). Blood adrenocorticotropic hormone (ACTH) and cortisol concentration were studied in 3 stages: I -preoperative, II--operation traumatic stage, III--the 1st postoperative days. The other indicators (heart rate, systolic blood pressure--SBP, dyastolic blood pressure--DBR average blood pressure--BP ave., pulse oximetry SpO₂, ECG, gases in blood and acid-base balance, electrolytes, blood glucose level, myocardium oxygen demand--MOD) were registered after 20 minutes and the 2nd day after operation besides the above stages. The research results indicated that it is possible to define the vegetative nervous system type superiority based on complex of single tests data, EEG, ECG, Cerdo Vegetative Index, Hildebrandt coefficient. CAEC can be considered optimun alternative of general anesthesia ensuring neurohumoral and hemodynamic stability in large scale, traumatic operations on abdominal cavity organs. Clinical course of CAEC is characterized by firmer hemodynamic and humoral stability in patients with functional balance of sympathetic and parasympathetic divisions of vegetative nervous system, that is in normotonics in comparison with sympathico-, and parasympathotonics.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Monitoring Domoic Acid production by Solid Phase Adsorption Toxin Tracking off the Santa Cruz Municipal Warf, Santa Cruz, California

NASA Astrophysics Data System (ADS)

Nolan, M.; Ziccarelli, L.; Kudela, R. M.

2013-12-01

Certain species of the diatom genus Pseudo-nitzschia are producers of the neurotoxin, domoic acid (DA). DA is known to cause amnesic shellfish poisoning also known as domoic acid poisoning, which can lead to permanent brain damage in humans and marine mammals. DA accumulates at higher trophic levels, generally due to consumption of toxic cells or through trophic transfer, and can potentially cause death of both humans and marine wildlife. The Santa Cruz Municipal Warf experiences periodic rises in DA concentrations, which can reach toxic levels in shellfish, fish, and other marine organisms. While these increases in toxicity often occur during Pseudo-nitzschia blooms, several periods of elevated DA have occurred when diatom abundance is restricted and/or dominated by non-toxic species, and there is increasing evidence that DA dissolved in seawater may be prevalent. One theory suggests that senescent or dead Pseudo-nitzschia cells sink to the benthos while retaining their toxin and are buried in sediment following the death of a bloom. Therefore, DA may accumulate in the benthos, where it is eventually released during storms or wave and tide conditions that disturb the sediment. We sampled DA in situ using Solid Phase Adsorption Toxin Tracking (SPATT) bags SPATT uses a synthetic resin to capture dissolved DA, allowing for the determination of integrated DA concentrations at known time intervals. The alternative method is mussel biotoxin monitoring, but it is less accurate due to uncertainties in the time of DA accumulation within the mussel, and the lack of uptake of dissolved DA by the mussel. We deployed and collected SPATT off the Santa Cruz Municipal Wharf at multiple depths beginning in February 2013. We expect to see increasing DA following the death of a harmful algal bloom. Under pre-bloom conditions, little to no DA has been detected in mussels or surface SPATT, but DA from SPATT is frequently observed at depth, suggesting that the sediment is exposed to (or acts as a reservoir for) DA, and that benthic organisms are chronically exposed to DA.

Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

PubMed

de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

2016-01-01

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

Is the Dark Side of the Moon Ever Illuminated by the Sun? (Breton Title: O Lado Escuro da Lua Nunca Apanha Sol?) El Lado Oscuro de la Luna Nunca Toma Sol?

NASA Astrophysics Data System (ADS)

Giovannini, Odilon; Pellenz, Daiana; Catelli, Francisco

2014-07-01

This work presents the elaboration of an answer to the question "Is the dark side of the moon ever illuminated by the sun?", in which issues related to the students' conceptions, how they arise, and the core elements that constitute a "good answer" are considered. These issues are initially elaborated from a literature review of the research in the field; then, and also based on this review, a didactic model that involves the relative motions of the Earth - Moon - Sun system is proposed. A description of the application of this model in a learning environment within middle school students is described. This work confirms the students' initial concepts described in the literature; on the other hand, the questions asked by students during the activity provide evidence that meaningful learning, at least to some degree, has occurred. Este trabalho apresenta a elaboração de uma resposta à pergunta "O lado escuro da Lua nunca apanha sol?" na qual são consideradas questões relacionadas às concepções iniciais dos alunos, de onde elas surgem e os elementos centrais que constituem uma "boa resposta". Essas questões são tratadas, inicialmente, a partir de uma revisão da literatura sobre pesquisas na área e, em seguida, também com base nessa revisão, um objeto modelo didático que envolve os movimentos relativos do sistema Terra - Lua - Sol é proposto. Uma descrição detalhada da aplicação deste modelo em um ambiente de aprendizagem com alunos do ensino fundamental é relatada. As concepções iniciais apresentadas na literatura se confirmam e os questionamentos feitos pelos estudantes por ocasião da aplicação do modelo fornecem indícios de que uma aprendizagem significativa, pelo menos em algum grau, ocorreu. El artículo se presenta el desarrollo de una respuesta a la pregunta "¿El lado oscuro de la luna nunca toma sol?", en la que se consideran algunas cuestiones vinculadas que se refieren a las concepciones iniciales de los estudiantes, dónde surgen y los elementos básicos que componen una "respuesta correcta". Estas cuestiones se tratan inicialmente a partir de una revisión bibliográfica de la investigación en el área; seguidamente, y también sobre la base de ésta revisión, se propone un modelo didáctico que ejemplifica los movimientos relativos del sistema Tierra - Luna - Sol. Se describe a continuación una aplicación de este modelo en un entorno de aprendizaje con alumnos del ciclo primario. Los conceptos iniciales presentados en la literatura se confirman y las cuestiones planteadas por los estudiantes durante la implementación del modelo proporcionan evidencia de que se ha producido un aprendizaje significativo, al menos en cierta medida.

Lesion of medial prefrontal dopamine terminals abolishes habituation of accumbens shell dopamine responsiveness to taste stimuli.

PubMed

Bimpisidis, Zisis; De Luca, Maria Antonietta; Pisanu, Augusta; Di Chiara, Gaetano

2013-02-01

Taste stimuli increase extracellular dopamine (DA) in the nucleus accumbens (NAc) and in the medial prefrontal cortex (mPFC). This effect shows single-trial habituation in NAc shell but not in core or in mPFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in mPFC. These observations support the hypothesis of an inhibitory influence of mPFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of mPFC 6-hydroxy-dopamine (6-OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6-OHDA was infused bilaterally in the mPFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6-OHDA infusion reduced tissue DA in the mPFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the mPFC. mPFC 6-OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre-exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre-exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top-down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Complicated function of dopamine in Aβ-related neurotoxicity: Dual interactions with Tyr10 and SNK(26-28) of Aβ.

PubMed

Liu, Mengmeng; Kou, Lu; Bin, Yannan; Wan, Liping; Xiang, Juan

2016-11-01

With the capability to inhibit the formation of amyloid β peptides (Aβ) fibril, dopamine (DA) and other catechol derivatives have been considered for the potential treatment of Alzheimer's disease (AD). Such treatment, however, remains debatable because of the diverse functions of Aβ and DA in AD pathology. Moreover, the complicated oxidation accompanying DA has caused the majority of the previous research to focus on the binding of DA oxides onto Aβ. The molecular mechanism by which Aβ interacts with the reduction state of DA, which is correlative with the brain function, should be urgently explored. By controlling rigorous anaerobic experimental conditions, this work investigated the molecular mechanism of the Aβ/DA interaction, and two binding sites were revealed. For the binding of DA, Tyrosine (Tyr 10 ) was identified as the strong binding site, and serine-asparagine-lysing (SNK(26-28)) segment was the weak binding segment. Furthermore, the Thioflavin T (THT) fluorescence confirmed DA's positive function of inhibiting Aβ aggregation through its weakly binding with SNK(26-28) segment. Meanwhile, 7-OHCCA fluorescence exhibited DA's negative function of enhancing OH generation through inhibiting the Aβ/Cu 2+ coordination. The viability tests of the neuroblastoma SH-SY5Y cells displayed that the coexistence of DA, Cu 2+ , and Aβ induced lower cell viability than free Cu 2+ , indicating the significant negative effect of excessive DA on AD progression. This research revealed the potential DA-induced damage in AD brain, which is significant for understanding the function of DA in AD neuropathology and for designing a DA-related therapeutic strategy for AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Intranasal administration of dopamine attenuates unconditioned fear in that it reduces restraint-induced ultrasound vocalizations and escape from bright light.

PubMed

Talbot, Teddy; Mattern, Claudia; de Souza Silva, Maria Angelica; Brandão, Marcus Lira

2017-06-01

Although substantial evidence suggests that dopamine (DA) enhances conditioned fear responses, few studies have examined the role of DA in unconditioned fear states. Whereas DA does not cross the blood-brain barrier, intranasally-applied dopamine reaches the brain directly via the nose-brain pathways in rodents, providing an alternative means of targeting DA receptors. Intranasal dopamine (IN-DA) has been demonstrated to bind to DA transporters and to increase extracellular DA in the striatum as well as having memory-promoting effects in rats. The purpose of this study was to examine the influence of IN-DA in three tests of fear/anxiety. The three doses of DA hydrochloride (0.03, 0.3, or 1 mg/kg) were applied in a viscous castor oil gel in a volume of 5 µl to each of both nostrils of adult Wistar rats prior to testing of (a) escape from a bright light, using a two-chamber procedure, (b) restraint-induced 22 kHz ultrasound vocalizations (USVs), and (c) exploratory behavior in the elevated plus-maze (EPM). IN-DA dose-dependently reduced escape from bright light and the number of USV responses to restraint. It had no influence on the exploratory behavior in the EPM. IN-DA application reduced escape behavior in two tests of unconditioned fear (escape from bright light and USV response to immobilization). These findings may be interpreted in light of the known antidepressant action of IN-DA and DA reuptake blockers. The results also confirm the promise of the nasal route as an alternative means for targeting the brain's dopaminergic receptors with DA.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

PubMed

Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

2017-07-01

Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits.

PubMed Central

Fearnley, I M; Finel, M; Skehel, J M; Walker, J E

1991-01-01

The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit. Images Fig. 1. PMID:1832859

Advancing Data Assimilation in Operational Hydrologic Forecasting: Progresses, Challenges, and Emerging Opportunities

NASA Technical Reports Server (NTRS)

Liu, Yuqiong; Weerts, A.; Clark, M.; Hendricks Franssen, H.-J; Kumar, S.; Moradkhani, H.; Seo, D.-J.; Schwanenberg, D.; Smith, P.; van Dijk, A. I. J. M.;

Assessment of SWE data assimilation for ensemble streamflow predictions

NASA Astrophysics Data System (ADS)

Franz, Kristie J.; Hogue, Terri S.; Barik, Muhammad; He, Minxue

2014-11-01

An assessment of data assimilation (DA) for Ensemble Streamflow Prediction (ESP) using seasonal water supply hindcasting in the North Fork of the American River Basin (NFARB) and the National Weather Service (NWS) hydrologic forecast models is undertaken. Two parameter sets, one from the California Nevada River Forecast Center (RFC) and one from the Differential Evolution Adaptive Metropolis (DREAM) algorithm, are tested. For each parameter set, hindcasts are generated using initial conditions derived with and without the inclusion of a DA scheme that integrates snow water equivalent (SWE) observations. The DREAM-DA scenario uses an Integrated Uncertainty and Ensemble-based data Assimilation (ICEA) framework that also considers model and parameter uncertainty. Hindcasts are evaluated using deterministic and probabilistic forecast verification metrics. In general, the impact of DA on the skill of the seasonal water supply predictions is mixed. For deterministic (ensemble mean) predictions, the Percent Bias (PBias) is improved with integration of the DA. DREAM-DA and the RFC-DA have the lowest biases and the RFC-DA has the lowest Root Mean Squared Error (RMSE). However, the RFC and DREAM-DA have similar RMSE scores. For the probabilistic predictions, the RFC and DREAM have the highest Continuous Ranked Probability Skill Scores (CRPSS) and the RFC has the best discrimination for low flows. Reliability results are similar between the non-DA and DA tests and the DREAM and DREAM-DA have better reliability than the RFC and RFC-DA for forecast dates February 1 and later. Despite producing improved streamflow simulations in previous studies, the hindcast analysis suggests that the DA method tested may not result in obvious improvements in streamflow forecasts. We advocate that integration of hindcasting and probabilistic metrics provides more rigorous insight on model performance for forecasting applications, such as in this study.

Wirelessly controlled micro- and nanostructures for bioapplications

NASA Astrophysics Data System (ADS)

Lindo, Andre Machado

Apresentar uma contribuicao para a caracterizacao e compreensao do comportamento hidrodinâmico da laguna Ria de Aveiro, baseada num estudo experimental e num estudo de modelacao numerica, e o objectivo deste trabalho. As caracteristicas hidrologicas da Ria de Aveiro foram investigadas atraves da realizacao de varias campanhas de amostragem, tendo sido efectuadas medicoes de altura de agua, salinidade, temperatura da agua e velocidade da corrente em varias estacoes distribuidas ao longo de quatro canais principais da laguna. None

Ultrasonic irradiation enhanced the ability of Fluorescein-DA-Fe(III) on sonodynamic and sonocatalytic damages of DNA molecules.

PubMed

Wu, Qiong; Chen, Xia; Jia, Lizhen; Wang, Yi; Sun, Ying; Huang, Xingjun; Shen, Yuxiang; Wang, Jun

2017-11-01

The interaction of DNA with Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein-Ferrous(III) (Fluorescein-DA-Fe(III)) with dual functional (sonodynamic and sonocatalytic) activity was studied by UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. And then, the damage of DNA caused by Fluorescein-DA-Fe(III) under ultrasonic irradiation (US) was researched by agarose gel electrophoresis and cytotoxicity assay. Meanwhile, some influenced factors such as ultrasonic irradiation time and Fluorescein-DA-Fe(III) concentration on the damage degree of DNA molecules were also examined. As a control, for Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein (Fluorescein-DA), the same experiments were carried out. The results showed that both Fluorescein-DA-Fe(III) and Fluorescein-DA can interact with DNA molecules. Under ultrasonic irradiation, Fluorescein-DA shows sonodynamic activity, which can damage DNA molecules. While, in the presence of Fe(III) ion, the Fluorescein-DA-Fe(III) displays not only sonodynamic activity but also sonocatalytic activity under ultrasonic irradiation, which injures DNA more serious than Fluorescein-DA. The researches confirmed the dual function (sonodynamic activity and sonocatalytic activity) of Fluorescein-DA-Fe(III) and expanded the usage of Fluorescein-DA-Fe(III) as a sonosensitizer in sonodynamic therapy (SDT). Copyright © 2017 Elsevier B.V. All rights reserved.

Impact cratering calculations

NASA Technical Reports Server (NTRS)

Ahrens, Thomas J.; Okeefe, J. D.; Smither, C.; Takata, T.

1991-01-01

In the course of carrying out finite difference calculations, it was discovered that for large craters, a previously unrecognized type of crater (diameter) growth occurred which was called lip wave propagation. This type of growth is illustrated for an impact of a 1000 km (2a) silicate bolide at 12 km/sec (U) onto a silicate half-space at earth gravity (1 g). The von Misses crustal strength is 2.4 kbar. The motion at the crater lip associated with this wave type phenomena is up, outward, and then down, similar to the particle motion of a surface wave. It is shown that the crater diameter has grown d/a of approximately 25 to d/a of approximately 4 via lip propagation from Ut/a = 5.56 to 17.0 during the time when rebound occurs. A new code is being used to study partitioning of energy and momentum and cratering efficiency with self gravity for finite-sized objects rather than the previously discussed planetary half-space problems. These are important and fundamental subjects which can be addressed with smoothed particle hydrodynamic (SPH) codes. The SPH method was used to model various problems in astrophysics and planetary physics. The initial work demonstrates that the energy budget for normal and oblique impacts are distinctly different than earlier calculations for silicate projectile impact on a silicate half space. Motivated by the first striking radar images of Venus obtained by Magellan, the effect of the atmosphere on impact cratering was studied. In order the further quantify the processes of meteor break-up and trajectory scattering upon break-up, the reentry physics of meteors striking Venus' atmosphere versus that of the Earth were studied.

Entropy driven chain effects on ligation chemistry† †Electronic supplementary information (ESI) available: Synthetic details, applied MHKS parameters, SEC chromatograms of all samples, (HT) NMR data, experimental debonding values, SANS measurements, computational data (energy contributions and geometries in the form of Gaussian archive entries). See DOI: 10.1039/c4sc02908a Click here for additional data file.

PubMed Central

Pahnke, Kai; Brandt, Josef; Gryn'ova, Ganna; Lindner, Peter; Schweins, Ralf; Schmidt, Friedrich Georg

2015-01-01

We report the investigation of fundamental entropic chain effects that enable the tuning of modular ligation chemistry – for example dynamic Diels–Alder (DA) reactions in materials applications – not only classically via the chemistry of the applied reaction sites, but also via the physical and steric properties of the molecules that are being joined. Having a substantial impact on the reaction equilibrium of the reversible ligation chemistry, these effects are important when transferring reactions from small molecule studies to larger or other entropically very dissimilar systems. The effects on the DA equilibrium and thus the temperature dependent degree of debonding (%debond) of different cyclopentadienyl (di-)functional poly(meth-)acrylate backbones (poly(methyl methacrylate), poly(iso-butyl methacrylate), poly(tert-butyl methacrylate), poly(iso-butyl acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(methyl acrylate) and poly(isobornyl acrylate)), linked via a difunctional cyanodithioester (CDTE) were examined via high temperature (HT) NMR spectroscopy as well as temperature dependent (TD) SEC measurements. A significant impact of not only chain mass and length with a difference in the degree of debonding of up to 30% for different lengths of macromonomers of the same polymer type but – remarkably – as well the chain stiffness with a difference in bonding degrees of nearly 20% for isomeric poly(butyl acrylates) is found. The results were predicted, reproduced and interpreted via quantum chemical calculations, leading to a better understanding of the underlying entropic principles. PMID:29560194

The da vinci robot system eliminates multispecialty surgical trainees' hand dominance in open and robotic surgical settings.

PubMed

Badalato, Gina M; Shapiro, Edan; Rothberg, Michael B; Bergman, Ari; RoyChoudhury, Arindam; Korets, Ruslan; Patel, Trushar; Badani, Ketan K

2014-01-01

Handedness, or the inherent dominance of one hand's dexterity over the other's, is a factor in open surgery but has an unknown importance in robot-assisted surgery. We sought to examine whether the robotic surgery platform could eliminate the effect of inherent hand preference. Residents from the Urology and Obstetrics/Gynecology departments were enrolled. Ambidextrous and left-handed subjects were excluded. After completing a questionnaire, subjects performed three tasks modified from the Fundamentals of Laparoscopic Surgery curriculum. Tasks were performed by hand and then with the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, California). Participants were randomized to begin with using either the left or the right hand, and then switch. Left:right ratios were calculated from scores based on time to task completion. Linear regression analysis was used to determine the significance of the impact of surgical technique on hand dominance. Ten subjects were enrolled. The mean difference in raw score performance between the right and left hands was 12.5 seconds for open tasks and 8 seconds for robotic tasks (P<.05). Overall left-right ratios were found to be 1.45 versus 1.12 for the open and robot tasks, respectively (P<.05). Handedness significantly differed between robotic and open approaches for raw time scores (P<.0001) and left-right ratio (P=.03) when controlling for the prior tasks completed, starting hand, prior robotic experience, and comfort level. These findings remain to be validated in larger cohorts. The robotic technique reduces hand dominance in surgical trainees across all task domains. This finding contributes to the known advantages of robotic surgery.

Domoic acid toxicokinetics in Dungeness crabs: new insights into mechanisms that regulate bioaccumulation.

PubMed

Schultz, Irvin R; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

2013-09-15

Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20mg/kg. After a 1mg/kg oral dose, DA disappeared from the foregut within 2h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100-1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (Vss) was 123-197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA uptake and distribution is regulated by crustacean orthologs of ATP-binding cassette (ABC) type transporters. We tested this hypothesis by co-exposing crabs to DA and known inhibitors of ABC transporters (verapamil, cyclosporine A and MK-571) and through in vitro studies using isolated hepatopancreas tissue and mixed cell suspensions prepared from hepatopancreas tissue. The in vivo results were inconclusive in that the toxicokinetics of DA was not consistently altered by co-administration of the inhibitors. Two exceptions were MK-571, which significantly increased the total body clearance of DA and co-administration of verapamil, which significantly increased the hepatopancreas tissue content of DA 24h after IV injection. Isolated pieces of hepatopancreas tissue were able to readily absorb DA from incubation media, but mixed cell suspensions did not. The absorption of DA or lack thereof was largely unaffected by co-incubation with verapamil although cell suspensions appeared to accumulate small quantities of DA in the presence of verapamil. Collectively, the results of this study suggest DA accumulates in the extracellular spaces of the hepatopancreas, such as the tubular lumen. Under natural circumstances, crabs feeding on contaminated shellfish would be expected to readily absorb DA, which is then stored and slowly eliminated in urine. If the DA exposure level exceeds the storage capacity of the tissue (as occurred with the 20mg/kg dose), breakthrough occurs resulting in much higher systemic exposure and potential for DA toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Pathomechanisms of Dopamine Dysregulation in DYT1 Dystonia: Targets for Therapeutics

DTIC Science & Technology

2016-10-01

DA release in DYT1(ΔE) knockin mice by assessing VMAT2 function, vesicle utilization, the ultrastructure of DA terminals, and D2 DA...in slice, the ultrastructure of DA terminals, D2 DA autoreceptor function nicotinic AChR (nAChR) heteroreceptors function. 2) To determine the

Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation.

PubMed

Sapountzi, Vasileia; Logan, Ian R; Nelson, Glyn; Cook, Susan; Robson, Craig N

2008-01-01

Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat-interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function.

Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release

PubMed Central

Acevedo-Rodriguez, Alexandra; Zhang, Lifen; Zhou, Fuwen; Gong, Suzhen; Gu, Howard; De Biasi, Mariella; Zhou, Fu-Ming; Dani, John A.

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. PMID:25237305

Determination of Domoic Acid in Plankton Net Samples from Golden Horn Estuary, Turkey, Using HPLC with Fluorescence Detection.

PubMed

Dursun, Fuat; Ünlü, Selma; Yurdun, Türkan

2018-03-01

This study focused on the fluctuations of domoic acid (DA) levels in plankton net samples collected from the Golden Horn Estuary (GHE), Turkey, between August 2011 and July 2012. DA concentrations were determined by high-performance liquid chromatography (HPLC), using a fluorenylmethoxycarbonyl (FMOC) derivatization technique. Monthly and biweekly data were evaluated with environmental variables, and their influence on DA production is discussed. DA levels in plankton net samples varied between 0.36 and 94.34 µg L - 1 . DA levels showed remarkable seasonal variation and they were generally higher in May, 2012, but no DA was detected between February and April, 2012. DA production was mostly controlled by temperature, with nitrate and silicate limitations being secondary factors that influenced DA concentrations.

Packaging of the virion host shutoff (Vhs) protein of herpes simplex virus: two forms of the Vhs polypeptide are associated with intranuclear B and C capsids, but only one is associated with enveloped virions.

PubMed

Read, G Sullivan; Patterson, Mary

2007-02-01

The virion host shutoff (Vhs) protein (UL41) is a minor component of herpes simplex virus virions which, following penetration, accelerates turnover of host and viral mRNAs. Infected cells contain 58-kDa and 59.5-kDa forms of Vhs, which differ in the extent of phosphorylation, yet only a 58-kDa polypeptide is incorporated into virions. In pulse-chase experiments, the primary Vhs translation product comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the 58-kDa virion polypeptide, and could be chased to 59.5 kDa. While both 59.5-kDa and 58-kDa forms were found in nuclear and cytoplasmic fractions, the 59.5-kDa form was significantly enriched in the nucleus. Both forms were associated with intranuclear B and C capsids, yet only the 58-kDa polypeptide was found in enveloped cytoplasmic virions. A 58-kDa form, but not the 59.5-kDa form, was found in L particles, noninfectious particles that contain an envelope and tegument but no capsid. The data suggest that virions contain two populations of Vhs that are packaged by different pathways. In the first pathway, the primary translation product is processed to 59.5 kDa, is transported to the nucleus, binds intranuclear capsids, and is converted to 58 kDa at some stage prior to final envelopment. The second pathway does not involve the 59.5-kDa form or interactions between Vhs and capsids. Instead, the primary translation product is phosphorylated to the 58-kDa virion form and packaged through interactions with other tegument proteins in the cytoplasm or viral envelope proteins at the site of final envelopment.

Within-family environmental transmission of drug abuse: a Swedish national study.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2013-02-01

CONTEXT Drug abuse (DA) strongly runs in families. Does this result solely from genetic factors or does the family environment contribute? OBJECTIVE To determine the familial environmental contribution to the risk for DA. DESIGN Follow-up in 9 public databases (1961-2009) in siblings and spouses. SETTING Sweden. PARTICIPANTS A total of 137 199 sibling pairs and 7561 spousal pairs containing a proband with DA and matched control probands. MAIN OUTCOME MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS In the best-fit model, which contained significant linear, quadratic, and cubic effects, among full sibling pairs containing a proband with DA, the relative risk for DA in the sibling declined from more than 6.0 for siblings born within 2 years of each other to less than 4.5 when born 10 years apart. Controlling for age differences in full sibling pairs, the hazard rate for DA in a sibling when the affected proband was older vs younger was 1.42 (95% CI, 1.31-1.54). In the best-fit model, which contained significant linear, quadratic, and cubic effects, among spousal pairs containing a proband with DA, the relative risk for DA in the spouse declined from more than 25.0 within 1 year of proband DA registration to 6.0 after 5 years. CONCLUSIONS Controlling for genetic effects by examining only full siblings, sibling resemblance for the risk for DA was significantly greater in pairs closer vs more distant in age. Older siblings more strongly transmitted the risk for DA to their younger siblings than vice versa. After one spouse is registered for DA, the other spouse has a large short-lived increase in DA risk. These results support strong familial environmental influences on DA at various life stages. A complete understanding of the familial transmission of DA will require knowledge of how genetic and familial environmental risk factors act and interact over development.

DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

PubMed

Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

2015-01-01

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Toward development of an in vitro model of methamphetamine-induced dopamine nerve terminal toxicity.

PubMed

Kim, S; Westphalen, R; Callahan, B; Hatzidimitriou, G; Yuan, J; Ricaurte, G A

2000-05-01

To develop an in vitro model of methamphetamine (METH)-induced dopamine (DA) neurotoxicity, striatal synaptosomes were incubated at 37 degrees C with METH for different periods of time (10-80 min), washed once, then tested for DA transporter function at 37 degrees C. METH produced time- and dose-dependent reductions in the V(max) of DA uptake, without producing any change in K(m). Incubation of synaptosomes with the DA neurotoxins 1-methyl-4-phenyl-pyridinium ion, 6-hydroxydopamine, and amphetamine under similar conditions produced comparable effects. In contrast, incubation with fenfluramine, a serotonin neurotoxin, did not. METH-induced decreases in DA uptake were selective, insofar as striatal glutamate uptake was unaffected. Various DA transporter blockers (cocaine, methylphenidate, and bupropion) afforded complete protection against METH-induced decreases in DA uptake, without producing any effect themselves. METH's effects were also temperature dependent, with greater decreases in DA uptake occurring at higher temperatures. Tests for residual drug revealed small amounts (0.1-0.2 microM) of remaining METH, but kinetic studies indicated that decreases in DA uptake were not likely to be due to METH acting as a competitive inhibitor of DA uptake. Decreases in the V(max) of DA uptake were not accompanied by decreases in B(max) of [(3)H]WIN 35,428 binding, possibly because there is no mechanism for removing damaged DA nerve endings from the in vitro preparation Collectively, these results give good support to the development of a valid in vitro model that may prove helpful for elucidating the mechanisms underlying METH-induced DA neurotoxicity.

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Wagner, Amy K

2017-06-05

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Prognosis of carotid dissecting aneurysms

PubMed Central

Larsson, Susanna C.; King, Alice; Madigan, Jeremy; Levi, Christopher; Norris, John W.

2017-01-01

Objective: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA. Methods: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA. Results: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10–7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA. Conclusions: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered. PMID:28087823

A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

PubMed Central

Bernhard, Nirit; van der Kooy, Derek

2000-01-01

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

USDA-ARS?s Scientific Manuscript database

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons.

PubMed

Diaz-Ruiz, Oscar; Zhang, Yajun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R; Tagliaferro, Adriana; Brusco, Alicia; Bäckman, Cristina M

2012-07-20

In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine-induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories.

Genetic Dissection of Midbrain Dopamine Neuron Development in vivo

PubMed Central

Ellisor, Debra; Rieser, Caroline; Voelcker, Bettina; Machan, Jason T.; Zervas, Mark

2012-01-01

Midbrain dopamine (MbDA) neurons are partitioned into medial and lateral cohorts that control complex functions. However, the genetic underpinnings of MbDA neuron heterogeneity are unclear. While it is known that Wnt1-expressing progenitors contribute to MbDA neurons, the role of Wnt1 in MbDA neuron development in vivo is unresolved. We show that mice with a spontaneous point mutation in Wnt1 have a unique phenotype characterized by the loss of medial MbDA neurons concomitant with a severe depletion of Wnt1-expressing progenitors and diminished LMX1a-expressing progenitors. Wnt1 mutant embryos also have alterations in a hierarchical gene regulatory loop suggesting multiple gene involvement in the Wnt1 mutant MbDA neuron phenotype. To investigate this possibility, we conditionally deleted Gbx2, Fgf8, and En1/2 after their early role in patterning and asked whether these genetic manipulations phenocopied the depletion of MbDA neurons in Wnt1 mutants. The conditional deletion of Gbx2 did not result in re-positioning or distribution of MbDA neurons. The temporal deletion of Fgf8 did not result in the loss of either LMX1a-expressing progenitors nor the initial population of differentiated MbDA neurons, but did result in a complete loss of MbDA neurons at later stages. The temporal deletion and species specific manipulation of En1/2 demonstrated a continued and species specific role of Engrailed genes in MbDA neuron development. Notably, our conditional deletion experiments revealed phenotypes dissimilar to Wnt1 mutants indicating the unique role of Wnt1 in MbDA neuron development. By placing Wnt1, Fgf8, and En1/2 in the context of their temporal requirement for MbDA neuron development, we further deciphered the developmental program underpinning MbDA neuron progenitors. PMID:23041116

Synergistic electron transfer effect-based signal amplification strategy for the ultrasensitive detection of dopamine.

PubMed

Lu, Qiujun; Chen, Xiaogen; Liu, Dan; Wu, Cuiyan; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

2018-05-15

The selective and sensitive detection of dopamine (DA) is of great significance for the identification of schizophrenia, Huntington's disease, and Parkinson's disease from the perspective of molecular diagnostics. So far, most of DA fluorescence sensors are based on the electron transfer from the fluorescence nanomaterials to DA-quinone. However, the limited electron transfer ability of the DA-quinone affects the level of detection sensitivity of these sensors. In this work, based on the DA can reduce Ag + into AgNPs followed by oxidized to DA-quinone, we developed a novel silicon nanoparticles-based electron transfer fluorescent sensor for the detection of DA. As electron transfer acceptor, the AgNPs and DA-quinone can quench the fluorescence of silicon nanoparticles effectively through the synergistic electron transfer effect. Compared with traditional fluorescence DA sensors, the proposed synergistic electron transfer-based sensor improves the detection sensitivity to a great extent (at least 10-fold improvement). The proposed sensor shows a low detection limit of DA, which is as low as 0.1 nM under the optimal conditions. This sensor has potential applicability for the detection of DA in practical sample. This work has been demonstrated to contribute to a substantial improvement in the sensitivity of the sensors. It also gives new insight into design electron transfer-based sensors. Copyright © 2018. Published by Elsevier B.V.

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells.

PubMed

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-10-13

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.

Dehydroandrographolide, an iNOS inhibitor, extracted from from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells

PubMed Central

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-01-01

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer. PMID:26356821

Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.

PubMed

Radl, Daniela B; Zárate, Sandra; Jaita, Gabriela; Ferraris, Jimena; Zaldivar, Verónica; Eijo, Guadalupe; Seilicovich, Adriana; Pisera, Daniel

2008-01-01

Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis. 2008 S. Karger AG, Basel.

Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

PubMed

Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

2017-03-15

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Possibility of the transformation of eEF-2 (100 kDa) to eEF-2 (65 kDa) in the peptide elongation process in vitro.

PubMed

Gajko, A; Sredzińska, K; Galasiński, W; Gindzieński, A

1999-02-16

Two active eEF-2 polypeptides of approximately 100 and 65 kDa were copurified from rat liver cells and separated. The fate of eEF-2 (100 kDa) during its binding to ribosomes and in the translocation step of the peptide elongation process was investigated. It was shown that eEF-2 (100 kDa) did not change its form during the process of binding to the ribosomes. In the postribosomal supernatant, obtained from the postincubation mixture of the elongation process, only eEF-2 (65 kDa) was found. These results suggest that the form of eEF-2 (100 kDa), when bound to the ribosome during the elongation process, is transformed to eEF-2 (65 kDa). Copyright 1999 Academic Press.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Design of New Bridge-Ring Energetic Compounds Obtained by Diels-Alder Reactions of Tetranitroethylene Dienophile.

PubMed

He, Piao; Mei, Hao-Zheng; Wu, Le; Yang, Jun-Qing; Zhang, Jian-Guo; Cohen, Adva; Gozin, Michael

2018-03-29

The density functional theory method was employed to calculate three-dimensional structures for a series of novel explosophores. The design of new molecules (DA1-DA12) was based on the bridge-ring structures that could be formed via Diels-Alder (DA) reaction of selected nitrogen-rich dienes and tetranitroethylene dienophile. The feasibility of the proposed DA reactions was predicted on the basis of the molecular orbital theory. The strong interactions between the HOMO of dienes, with electron-donating groups (Diene2, Diene6, and Diene8), and the LUMO of tetranitroethylene dienophile suggested thermodynamically favorable formation of the desired DA reaction products. In addition to molecular structures of the explored DA compounds, their physicochemical and energetic properties were also calculated in detail. Due to compact bridge-ring structures, new energetic molecules have highly positive heats of formation (up to 1124.90 kJ·mol -1 ) and high densities (up to 2.04 g·cm -3 ). Also, as a result of all-right ratios of nitrogen and oxygen, most of the new compounds possess high detonation velocities (8.28-10.02 km·s -1 ) and high detonation pressures (30.87-47.83 GPa). Energetic compounds DA1, DA4, and DA12 exhibit a superior detonation performance over widely used HMX explosive, and DA5, DA7, and DA10 could be comparable to the state-of-the-art CL-20 and ONC explosives. Our proposed designs and synthetic methodology should provide a platform for the development of novel energetic materials with superior performance.

Heterotetrameric composition of aquaporin-4 water channels.

PubMed

Neely, J D; Christensen, B M; Nielsen, S; Agre, P

1999-08-24

Aquaporin (AQP) water channel proteins are tetrameric assemblies of individually active approximately 30 kDa subunits. AQP4 is the predominant water channel protein in brain, but immunoblotting of native tissues has previously yielded multiple poorly resolved bands. AQP4 is known to encode two distinct mRNAs with different translation initiating methionines, M1 or M23. Using SDS-PAGE urea gels and immunoblotting with anti-peptide antibodies, four polypeptides were identified in brain and multiple other rat tissues with the following levels of expression: 32 kDa > 34 kDa > 36 kDa > 38 kDa. The 34 and 38 kDa polypeptides react with an antibody specific for the N-terminus of the M1 isoform, and 32 and 36 kDa correspond to the shorter M23 isoform. Immunogold electron microscopic studies with rat cerebellum cryosections demonstrated that the 34 kDa polypeptide colocalizes in perivascular astrocyte endfeet where the 32 kDa polypeptide is abundantly expressed. Velocity sedimentation, cross-linking, and immunoprecipitation analyses of detergent-solubilized rat brain revealed that the 32 and 34 kDa polypeptides reside within heterotetramers. Immunoprecipitation of AQP4 expressed in Xenopus laevis oocytes demonstrated that heterotetramer formation reflects the relative expression levels of the 32 and 34 kDa polypeptides; however, tetramers containing different compositions of the two polypeptides exhibit similar water permeabilities. These studies demonstrate that AQP4 heterotetramers are formed from two overlapping polypeptides and indicate that the 22-amino acid sequence at the N-terminus of the 34 kDa polypeptide does not influence water permeability but may contribute to membrane trafficking or assembly of arrays.

Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone.

PubMed

Hryhorczuk, Cecile; Sheng, Zhenyu; Décarie-Spain, Léa; Giguère, Nicolas; Ducrot, Charles; Trudeau, Louis-Éric; Routh, Vanessa H; Alquier, Thierry; Fulton, Stephanie

2018-02-01

Long-chain fatty acids (FAs) act centrally to decrease food intake and hepatic glucose production and alter hypothalamic neuronal activity in a manner that depends on FA type and cellular transport proteins. However, it is not known whether FAs are sensed by ventral tegmental area (VTA) dopamine (DA) neurons to control food-motivated behavior and DA neurotransmission. We investigated the impact of the monounsaturated FA oleate in the VTA on feeding, locomotion, food reward, and DA neuronal activity and DA neuron expression of FA-handling proteins and FA uptake. A single intra-VTA injection of oleate, but not of the saturated FA palmitate, decreased food intake and increased locomotor activity. Furthermore, intra-VTA oleate blunted the rewarding effects of high-fat/sugar food in an operant task and inhibited DA neuronal firing. Using sorted DA neuron preparations from TH-eGFP mice we found that DA neurons express FA transporter and binding proteins, and are capable of intracellular transport of long-chain FA. Finally, we demonstrate that a transporter blocker attenuates FA uptake into DA neurons and blocks the effects of intra-VTA oleate to decrease food-seeking and DA neuronal activity. Together, these results suggest that DA neurons detect FA and that oleate has actions in the VTA to suppress DA neuronal activity and food seeking following cellular incorporation. These findings highlight the capacity of DA neurons to act as metabolic sensors by responding not only to hormones but also to FA nutrient signals to modulate food-directed behavior.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons

PubMed Central

Linehan, Victoria; Trask, Robert B.; Briggs, Chantalle; Rowe, Todd M.; Hirasawa, Michiru

2017-01-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups, where orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying DA action on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using whole cell patch clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration dependent, bidirectional manner. Low (1 μM) and high concentrations (100 μM) of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors, whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. PMID:26036709

Age, period and cohort trends in drug abuse hospitalizations within the total Swedish population (1975-2010)*

PubMed Central

Giordano, Giuseppe N.; Ohlsson, Henrik; Kendler, Kenneth S.; Winkleby, Marilyn A.; Sundquist, Kristina; Sundquist, Jan

2014-01-01

Background: The societal consequences of drug abuse (DA) are severe and well documented, the World Health Organization recommending tracking of population trends for effective policy responses in treatment of DA and delivery of health care services. However, to correctly identify possible sources of DA change, one must first disentangle three different time-related influences on the need for treatment due to DA: age effects, period effects and cohort effects. Methods: We constructed our main Swedish national DA database (spanning four decades) by linking healthcare data from the Swedish Hospital Discharge Register to individuals, which included hospitalisations in Sweden for 1975-2010. All hospitalized DA cases were identified by ICD codes. Our Swedish national sample consisted of 3,078,129 men and 2,921,816 women. We employed a cross-classified multilevel logistic regression model to disentangle any net age, period and cohort effects on DA hospitalization rates. Results: We found distinct net age, period and cohort effects, each influencing the predicted probability ofhospitalisation for DA in men and women. Peak age for DA in both sexes was 33-35 years; net period effects showed an increase in hospitalisation for DA from 1996 to 2001; and in birth cohorts 1968-74, we saw a considerable reduction (around 75%) in predicted probability of hospitalisation for DA. Conclusions: The use of hospital admissions could be regarded as a proxy of the population's health service use for DA. Our results may thus constitute a basis for effective prevention planning, treatment and other appropriate policy responses. PMID:24300899

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal

PubMed Central

Kaufling, Jennifer

2015-01-01

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA–VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA–VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. SIGNIFICANCE STATEMENT Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. PMID:26180204

Effect of gamma irradiation on the expressed proteins in the foodborne pathogen Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Trudeau, Karine; Dang Vu, Khanh; Shareck, François; Lacroix, Monique

2012-08-01

A capillary electrophoresis method with UV detection was developed to analyze protein composition of the foodborne pathogen Staphylococcus aureus. Bacterial samples containing 109 CFU/ml, obtained after two cycles of incubations of 24 h, were gamma irradiated at different doses of 1.2, 3.5 and 2.9 kGy to respectively create damage cells, to kill cells and to provoke viable but non cultivable cells (VBNC). It was observed that an irradiation at a sensitive dose of 1.2 kGy caused a significantly increase in the protein with molecular weight (MW) of 17.7 kDa (from 0.61% to 1.2%). This treatment also caused decreases in the expressed proteins with the MWs of 16.3 kDa (from 6.2% to 5.3%) and of 23.4 kDa (from 4.0% to 2.30%). Irradiation at a VBCN dose of 2.9 kGy caused increases in expressed proteins with the MWs of 17.7 kDa (from 0.61% to 3.43%), 18.7 kDa (from 1.04% to 4.30%), 19.5 kDa (from 0.71% to 2.30%), 21.1 kDa (from 1.20% to 3.80%). Moreover, this treatment (2.9 kGy) also caused significantly decreases (P≤0.05) in the expressed proteins with the MW of 30.7 kDa (from 8.6% to 5.15%), 36.3 kDa (from 3.1% to 2.7%) and 40.5 kDa (from 11.3% to 8.5%). Finally, for the irradiation at a lethal dose of 3.5 kGy, it can be found that the expressed proteins with the MW of 17.7 kDa, 18.7 kDa and 19.5 kDa were increased less than that of expressed proteins at the VCNC dose (2.9 kGy) and these might be the very important proteins which are responsible for the survival of the S. aureus. Further, there were also the decreases in expressed proteins with the MW of 30.7 kDa, 36.3 kDa and 75.1 kDa at this dose of treatment (3.5 kGy) which can be expected that these proteins are seriously affected at high dose of γ-irradiation treatment.

TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning.

PubMed

Luo, Sarah X; Timbang, Leah; Kim, Jae-Ick; Shang, Yulei; Sandoval, Kadellyn; Tang, Amy A; Whistler, Jennifer L; Ding, Jun B; Huang, Eric J

2016-12-20

Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Apomorphine and the dopamine hypothesis of schizophrenia: a dilemma?

PubMed Central

Dépatie, L; Lal, S

2001-01-01

The dopamine (DA) hypothesis of schizophrenia implicates an enhancement of DA function in the pathophysiology of the disorder, at least in the genesis of positive symptoms. Accordingly, apomorphine, a directly acting DA receptor agonist, should display psychotomimetic properties. A review of the literature shows little or no evidence that apomorphine, in doses that stimulate postsynaptic DA receptors, induces psychosis in non-schizophrenic subjects or a relapse or exacerbation of psychotic symptoms in patients with schizophrenia. After a detailed review of the literature reporting psychotogenic effects of apomorphine in patients with Parkinson's disease, an interpretation of these data is difficult, in part because of several confounding factors, such as the concomitant use of drugs known to induce psychosis and the advanced state of the progressive neurological disorder. In the context of the DA hypothesis of schizophrenia, the limited ability of apomorphine to induce psychosis, in contrast to indirectly acting DA agonists that increase synaptic DA, may be explained by the relatively weak affinity of apomorphine for the D3 receptor compared with DA. Alternatively, enhancement of DA function, though necessary, may be insufficient by itself to induce psychosis. PMID:11394190

Electrospray ionization mass analysis of normal and genetic variants of human serum albumin.

PubMed

Brennan, S O

1998-11-01

Both normal albumin (Al A) and genetically modified forms were isolated from six heterozygous subjects. Albumins from each individual were analyzed by electrospray ionization mass spectrometry (ESI MS), and the mass was compared with that predicted from the protein sequence. In all cases, the Al A was heterogeneous, with components of mass (+/- SE) 66463+/-4, 66586+/-3, and 66718+/-5 Da. Each genetic variant showed similar heterogeneity. The mass increase in Al Casebrook (2214 Da) was very close to that predicted (2205 Da) from protein and carbohydrate sequence analysis, whereas the increase in Al Redhill (2378 Da) was close to that expected (2392 Da) for an Arg-albumin with a disialylated N-linked biantennary oligosaccharide and an Ala-->Thr mutation. The circulating proalbumins, Christchurch and Blenheim, had mass increases of 748 and 756 Da, respectively, over Al A; in excellent agreement with theoretical values of 744 and 756. Clear shifts in mass were also detected for the point substitutions 177Cys-->Phe (44 Da), 1Asp-->Val (20 Da), and Arg-albumin (160 Da).

Time- and dose-related effects of a gonadotropin-releasing hormone agonist and dopamine antagonist on reproduction in the Northern leopard frog (Lithobates pipiens).

PubMed

Vu, Maria; Weiler, Bradley; Trudeau, Vance L

2017-12-01

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone release to control ovulation and spermiation in vertebrates. Dopamine (DA) has a clear inhibitory role in the control of reproduction in numerous teleosts, and emerging evidence suggests that similar mechanisms may exist in amphibians. The interactions between GnRH and DA on spawning success and pituitary gene expression in the Northern leopard frog (Lithobates pipiens) were therefore investigated. Frogs were injected during the natural breeding season with a GnRH agonist [GnRH-A; (Des-Gly 10 , D-Ala 6 , Pro-NHEt 9 )-LHRH; 0.1μg/g and 0.4μg/g] alone and in combination with the dopamine receptor D2 antagonist metoclopramide (MET; 5μg/g and 10μg/g). Injected animals were allowed to breed in outdoor mesocosms. Time to amplexus and oviposition were assessed, and egg mass release, incidences of amplexus, egg mass weight, total egg numbers and fertilization rates were measured. To examine gene expression, female pituitaries were sampled at 12, 24 and 36h following injection of GnRH-A (0.4μg/g) alone and in combination with MET (10μg/g). The mRNA levels of the genes lhb, fshb, gpha, drd2 and gnrhr1 were measured using quantitative real-time PCR. Data were analyzed by a two-way ANOVA. Both GnRH-A doses increased amplexus, oviposition and fertilization alone. Co-injection of MET with GnRH-A did not further enhance spawning success. Injection of GnRH-A alone time-dependently increased expression of lhb, fshb, gpha and gnrhr1. The major effect of MET alone was to decrease expression of drd2. Importantly, the stimulatory effects of GnRH-A on lhb, gpha and gnrhr1 were potentiated by the co-injection of MET at 36h. At this time, expression of fshb was increased only in animals injected with both GnRH-A and MET. Spawning success was primarily driven by the actions of GnRH-A. The hypothesized inhibitory action of DA was supported by pituitary gene expression analysis. The results from this study provide a fundamental framework for future time- and dose-response investigations to improve current spawning methods in amphibians. Copyright © 2017. Published by Elsevier Inc.

The First 24 Robotic Surgeries of Hospital da Luz.

PubMed

Eurico Reis, João; Santos Silva, João; Costa, Ana Rita; Palma Martelo, Fernando

2017-01-01

Robotic assisted thoracic surgery (RATS) has been growing all over the world, presenting itself as an improvement over video-assisted thoracic surgery (VATS). The main advantages are the precision of the movements, as well as the three-dimensional vision with the consequent perception of the depth of the surgical field. Thus, technically more difficult procedures, such as anatomic segmentectomies and bronchoplastic resections, are facilitated. This surgical approach also improves the quality of mediastinal lymph node dissection, extremely important in lung cancer patients. Analysis of the first 24 robotic thoracic surgeries performed at Hospital da Luz. All robotic thoracic surgeries performed at Hospital da Luz from 2/6/2016 to this date were evaluated, concerning diagnosis, type of surgery, chest drainage time, hospitalization time, morbidity and mortality. Twenty-four RATS were performed, with patients having a mean age of 60.5 (39-76) years, eleven of them being male. All surgeries were performed with 3 ports of 8mm and a 12mm port for the assistant. Eighteen surgeries of pulmonary resection (75%), five surgeries for mediastinal lesions (20.8%), and one for intercostal nerve harvest for reinnervation of the brachial plexus, were performed. In the pulmonary surgeries, eleven were lobectomies (61.1%), five were anatomic segmentectomies (27.8%) and two wedge resections (11.1%). Neoplastic disease was the reason for the sixteen lung anatomic resections, two for metastatic disease and fourteen for primary lung cancer. In each case, a systemic lymph node dissection was performed. All procedures were performed without intra- or postoperative complications. Mean drainage time was 3.4 days [2-6], and mean hospitalization time was 4.8 days [3-8]. There were no mortality or major morbidity. There were two patients with prolonged air-leak up to 6 days. The morbidity after discharge was 12.5%, consisting of an apical pneumothorax that resolved spontaneously, a basal pleural effusion that resolved with outpatient thoracentesis, and a respiratory infection treated with antibiotic. The overall evaluation of this technique is still precocious, but allows to affirm that an experienced surgeon in vats surgery has a faster learning curve with this new approach. The innovation and development of new techniques in thoracic surgery are fundamental in order to allow more effective treatments, with less pain and, when possible, lung parenchyma sparing surgeries in patients with early neoplastic lung disease.

Comparison of spectral estimators for characterizing fractionated atrial electrograms

PubMed Central

2013-01-01

Background Complex fractionated atrial electrograms (CFAE) acquired during atrial fibrillation (AF) are commonly assessed using the discrete Fourier transform (DFT), but this can lead to inaccuracy. In this study, spectral estimators derived by averaging the autocorrelation function at lags were compared to the DFT. Method Bipolar CFAE of at least 16 s duration were obtained from pulmonary vein ostia and left atrial free wall sites (9 paroxysmal and 10 persistent AF patients). Power spectra were computed using the DFT and three other methods: 1. a novel spectral estimator based on signal averaging (NSE), 2. the NSE with harmonic removal (NSH), and 3. the autocorrelation function average at lags (AFA). Three spectral parameters were calculated: 1. the largest fundamental spectral peak, known as the dominant frequency (DF), 2. the DF amplitude (DA), and 3. the mean spectral profile (MP), which quantifies noise floor level. For each spectral estimator and parameter, the significance of the difference between paroxysmal and persistent AF was determined. Results For all estimators, mean DA and mean DF values were higher in persistent AF, while the mean MP value was higher in paroxysmal AF. The differences in means between paroxysmals and persistents were highly significant for 3/3 NSE and NSH measurements and for 2/3 DFT and AFA measurements (p<0.001). For all estimators, the standard deviation in DA and MP values were higher in persistent AF, while the standard deviation in DF value was higher in paroxysmal AF. Differences in standard deviations between paroxysmals and persistents were highly significant in 2/3 NSE and NSH measurements, in 1/3 AFA measurements, and in 0/3 DFT measurements. Conclusions Measurements made from all four spectral estimators were in agreement as to whether the means and standard deviations in three spectral parameters were greater in CFAEs acquired from paroxysmal or in persistent AF patients. Since the measurements were consistent, use of two or more of these estimators for power spectral analysis can be assistive to evaluate CFAE more objectively and accurately, which may lead to improved clinical outcome. Since the most significant differences overall were achieved using the NSE and NSH estimators, parameters measured from their spectra will likely be the most useful for detecting and discerning electrophysiologic differences in the AF substrate based upon frequency analysis of CFAE. PMID:23855345

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax.

PubMed

Binger, Cathy; Kent-Walsh, Jennifer; King, Marika

2017-07-12

The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions-that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures.

Developmental analysis of the dopamine-containing neurons of the Drosophila brain

PubMed Central

Hartenstein, Volker; Cruz, Louie; Lovick, Jennifer K.; Guo, Ming

2016-01-01

The Drosophila dopaminergic (DA) system consists of a relatively small number of neurons clustered throughout the brain and ventral nerve cord. Previous work shows that clusters of DA neurons innervate different brain compartments, which in part accounts for functional diversity of the DA system. In this paper, we analyzed the association between DA neuron clusters and specific brain lineages, developmental and structural units of the Drosophila brain which provide a framework of connections that can be followed throughout development. The hatching larval brain contains six groups of primary DA neurons (born in the embryo), which we assign to six distinct lineages. We can show that all larval DA clusters persist into the adult brain. Some clusters increase in cell number during late larval stages while others do not become DA-positive until early pupa. Ablating neuroblasts with hydroxyurea (HU) prior to onset of larval proliferation (generates secondary neurons) confirms these added DA clusters are primary neurons born in the embryo, rather than secondary neurons. A single cluster that becomes DA-positive in the late pupa, PAM1/lineage DALcm1/2, forms part of a secondary lineage which can be ablated by larval HU application. By supplying lineage information for each DA cluster, our analysis promotes further developmental and functional analyses of this important system of neurons. PMID:27350102

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

Nearest clusters based partial least squares discriminant analysis for the classification of spectral data.

PubMed

Song, Weiran; Wang, Hui; Maguire, Paul; Nibouche, Omar

2018-06-07

Partial Least Squares Discriminant Analysis (PLS-DA) is one of the most effective multivariate analysis methods for spectral data analysis, which extracts latent variables and uses them to predict responses. In particular, it is an effective method for handling high-dimensional and collinear spectral data. However, PLS-DA does not explicitly address data multimodality, i.e., within-class multimodal distribution of data. In this paper, we present a novel method termed nearest clusters based PLS-DA (NCPLS-DA) for addressing the multimodality and nonlinearity issues explicitly and improving the performance of PLS-DA on spectral data classification. The new method applies hierarchical clustering to divide samples into clusters and calculates the corresponding centre of every cluster. For a given query point, only clusters whose centres are nearest to such a query point are used for PLS-DA. Such a method can provide a simple and effective tool for separating multimodal and nonlinear classes into clusters which are locally linear and unimodal. Experimental results on 17 datasets, including 12 UCI and 5 spectral datasets, show that NCPLS-DA can outperform 4 baseline methods, namely, PLS-DA, kernel PLS-DA, local PLS-DA and k-NN, achieving the highest classification accuracy most of the time. Copyright © 2018 Elsevier B.V. All rights reserved.

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity

PubMed Central

Wilson, Walter B.; Sander, Lane C.; Oña-Ruales, Jorge O.; Mössner, Stephanie G.; Sidisky, Leonard M.; Lee, Milton L.; Wise, Stephen A.

2017-01-01

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184 Da PASHs, (2) 13 four-ring MM 234 Da PASHs, (3) 10 five-ring MM 258 Da PASHs, and (4) 20 five-ring MM 284 Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r = 0.50 (MM 284 Da) to r = 0.77 (MM 234 Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r = 0.31 (MM 234 Da) to r = 0.54 (MM 284 Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r = 0.14 (MM 258 Da) to r = 0.59 (MM 284 Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. PMID:28089272

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity.

PubMed

Wilson, Walter B; Sander, Lane C; Oña-Ruales, Jorge O; Mössner, Stephanie G; Sidisky, Leonard M; Lee, Milton L; Wise, Stephen A

2017-02-17

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184Da PASHs, (2) 13 four-ring MM 234Da PASHs, (3) 10 five-ring MM 258Da PASHs, and (4) 20 five-ring MM 284Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r=0.50 (MM 284Da) to r=0.77 (MM 234Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r=0.31 (MM 234Da) to r=0.54 (MM 284Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r=0.14 (MM 258Da) to r=0.59 (MM 284Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. Published by Elsevier B.V.

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax

PubMed Central

Kent-Walsh, Jennifer; King, Marika

2017-01-01

Purpose The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Method Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Results Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions—that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. Conclusion DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures. PMID:28614580

Sequence and expression variations suggest an adaptive role for the DA1-like gene family in the evolution of soybeans.

PubMed

Zhao, Man; Gu, Yongzhe; He, Lingli; Chen, Qingshan; He, Chaoying

2015-05-15

The DA1 gene family is plant-specific and Arabidopsis DA1 regulates seed and organ size, but the functions in soybeans are unknown. The cultivated soybean (Glycine max) is believed to be domesticated from the annual wild soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the evolution of soybeans, we compared variation at both sequence and expression levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). Sequence identities were extremely high between the orthologous pairs between soybeans, while the paralogous copies in a soybean species showed a relatively high divergence. Moreover, the expression variation of DA1-like paralogous genes in soybean was much greater than the orthologous gene pairs between the wild and cultivated soybeans during development and challenging abiotic stresses such as salinity. We further found that overexpressing GsoDA1 genes did not affect seed size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed germination sensitivity to salt stress. Moreover, most of these genes could improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a detection of expression variation of several key genes in the salt-tolerance pathways. Our work suggested that expression diversification of DA1-like genes is functionally associated with adaptive radiation of soybeans, reinforcing that the plant-specific DA1 gene family might have contributed to the successful adaption to complex environments and radiation of the plants.

Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice.

PubMed

Klejbor, Ilona; Myers, Jason M; Hausknecht, Kathy; Corso, Thomas D; Gambino, Angelo S; Morys, Janusz; Maher, Pamela A; Hard, Robert; Richards, Jerry; Stachowiak, Ewa K; Stachowiak, Michal K

2006-06-01

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

PubMed

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

78 FR 46930 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Counseling and Information Sheet; DA Form 5434; OMB Control Number 0702-TBD. Needs And Uses: The information.... Frequency: On Occasion. SUPPLEMENTARY INFORMATION: Summary of Information Collection Respondents are DA Civilian employees and Soldiers. Departing Soldiers or DA Civilian employees complete the DA Form 5434...

dK/da effects on the SCC growth rates of nickel base alloys in high-temperature water

NASA Astrophysics Data System (ADS)

Chen, Kai; Wang, Jiamei; Du, Donghai; Andresen, Peter L.; Zhang, Lefu

2018-05-01

The effect of dK/da on crack growth behavior of nickel base alloys has been studied by conducting stress corrosion cracking tests under positive and negative dK/da loading conditions on Alloys 690, 600 and X-750 in high temperature water. Results indicate that positive dK/da accelerates the SCC growth rates, and the accelerating effect increases with dK/da and the initial CGR. The FRI model was found to underestimate the dK/da effect by ∼100X, especially for strain hardening materials, and this underscores the need for improved insight and models for crack tip strain rate. The effect of crack tip strain rate and dK/dt in particular can explain the dK/da accelerating effect.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making.

PubMed

St Onge, Jennifer R; Ahn, Soyon; Phillips, Anthony G; Floresco, Stan B

2012-11-21

Mesocorticolimbic dopamine (DA) has been implicated in cost/benefit decision making about risks and rewards. The prefrontal cortex (PFC) and nucleus accumbens (NAc) are two DA terminal regions that contribute to decision making in distinct manners. However, how fluctuations of tonic DA levels may relate to different aspects of decision making remains to be determined. The present study measured DA efflux in the PFC and NAc with microdialysis in well trained rats performing a probabilistic discounting task. Selection of a small/certain option always delivered one pellet, whereas another, large/risky option yielded four pellets, with probabilities that decreased (100-12.5%) or increased (12.5-100%) across four blocks of trials. Yoked-reward groups were also included to control for reward delivery. PFC DA efflux during decision making decreased or increased over a session, corresponding to changes in large/risky reward probabilities. Similar profiles were observed from yoked-rewarded rats, suggesting that fluctuations in PFC DA reflect changes in the relative rate of reward received. NAc DA efflux also showed decreasing/increasing trends over the session during both tasks. However, DA efflux was higher during decision making on free- versus forced-choice trials and during periods of greater reward uncertainty. Moreover, changes in NAc DA closely tracked shifts in choice biases. These data reveal dynamic and dissociable fluctuations in PFC and NAc DA transmission associated with different aspects of risk-based decision making. PFC DA may signal changes in reward availability that facilitates modification of choice biases, whereas NAc DA encodes integrated signals about reward rates, uncertainty, and choice, reflecting implementation of decision policies.

Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli.

PubMed

Bassareo, Valentina; Musio, Paolo; Di Chiara, Gaetano

2011-04-01

Drugs of abuse and palatable food share the ability to stimulate dopamine (DA) transmission in the nucleus accumbens shell. However, while the stimulation of shell DA by food undergoes habituation, that by drugs of abuse does not. This study aims to directly compare the changes of extracellular DA, by microdialysis, in shell and core and prefrontal cortex (PFCX) in response to food- and drug-conditioned stimuli (CSs). Rats were trace-conditioned by Fonzies box (FB) or vanilla box (VB; CS), followed by food: Fonzies, intraoral chocolate solution (food-unconditioned stimulus (US)) and morphine (1.0 mg/Kg sc; drug US). Control (unconditioned) rats received standard food instead of Fonzies, tap water instead of chocolate, saline instead of morphine. Food-CSs increased core but not shell DA, while drug-CSs did the opposite. Food and drug-CSs both increased PFCX DA. Exposure to food-CSs potentiated core and PFCX DA response to food while shell responsiveness was dependent upon the relative CS and US nature. If the CS was intrinsic to the food US (CS = FB/US = Fonzies) the response of shell DA to the US was abolished. If the CS was extrinsic to the food US (CS = FB/US = chocolate; CS = VB/US = Fonzies), shell DA increased in response to the US. Exposure to the drug-CS potentiated the DA response to the drug-US in the shell and in the PFCX, but not in the core. Drug-CSs differentially activate DA as compared to food-CSs in shell and core and differentially affect DA response to the US in these areas. These differences might be relevant for the role of DA in the mechanism of drug addiction.

Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene (hlyA) and characterization of the processed products.

PubMed

Yamamoto, K; Ichinose, Y; Shinagawa, H; Makino, K; Nakata, A; Iwanaga, M; Honda, T; Miwatani, T

1990-12-01

Vibrio cholerae O1 biotype El Tor produces and secretes a 65-kDa cytolysin/hemolysin into the culture medium. We cloned the structural gene (hlyA) for the cytolysin from the total DNA of a V. cholerae O1 El Tor strain, N86. Nucleotide sequence analysis of hlyA revealed an open reading frame consisting of 2,223 bp which can code for a protein of 741 amino acids with a molecular weight of 81,961. Consistent with this, a 79-kDa protein was identified as the product of hlyA by maxicell analysis in Escherichia coli. N-terminal amino acids of this 79-kDa HlyA protein and those of a 65-kDa El Tor cytolysin purified from V. cholerae were Asn-26 and Asn-158, respectively. The 82- and 79-kDa precursors of the 65-kDa mature cytolysin were found in V. cholerae by pulse-chase labeling and Western blot (immunoblot) analysis of hlyA products. Hemolytic activity of the 79-kDa HlyA protein from E. coli was less than 5% that for the 65-kDa cytolysin from V. cholerae. Our results suggest that in V. cholerae, the 82-kDa preprotoxin synthesized in the cytoplasm is secreted through the membranes into the culture medium as the 79-kDa inactive protoxin after cleavage of the signal peptide and is then further processed into the 65-kDa active cytolysin by release of the N-terminal 15-kDa fragment.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

PubMed

Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

2015-08-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The causal nature of the association between neighborhood deprivation and drug abuse: a prospective national Swedish co-relative control study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background Risk for drug abuse (DA) is strongly associated with neighborhood social deprivation (SD). However, the causal nature of this relationship is unclear. Method Three Swedish population-based cohorts were followed up over 5 years for incident registration of DA in medical, legal or pharmacy records. In each cohort, we examined the SD–DA association, controlling carefully for individual socio-economic status (SES) with multiple measures, in the entire sample and among pairs of first cousins, paternal and maternal half-siblings, full siblings and monozygotic (MZ) twins discordant for SD exposure. The number of informative relative pairs ranged from 6366 to 166208. Results In all cohorts, SD was prospectively related to risk for incident DA. In relative pairs discordant for SD exposure, the SD–DA association was similar to that seen in the entire population in cousins, half-siblings, full siblings and MZ twins. Eliminating subjects who were residentially unstable or had DA in the first two follow-up years did not alter this pattern. When divided by age, in the youngest groups, the SD–DA association was weaker in siblings than in the entire population. Conclusions Across three cohorts, controlling for individual SES and confounding familial factors, SD prospectively predicted risk for incident DA registration. These results support the hypothesis that the SD–DA association is in part causal and unlikely to result entirely from personal attributes, which both increase risk for DA and cause selection into high SD environments. At least part of the SD–DA association arises because exposure to SD causes an increased risk of DA. PMID:25055172

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

PubMed

Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

2016-11-01

Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

Insulin stimulates the tyrosine phosphorylation of a 61-kilodalton protein in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1992-03-01

Insulin stimulated the tyrosine phosphorylation of a 61-kilodalton (kDa) protein in rat adipocytes prelabeled for 2 h with [32P]orthophosphate. Tyrosine phosphorylation of this 61-kDa protein displayed very similar insulin concentration dependency to receptor autophosphorylation and tyrosine phosphorylation of a high molecular mass receptor substrate of 160 kDa. Phosphorylation of the 61-kDa protein was very rapid with maximum labeling attained at 30 sec, paralleling that of the other two proteins. Phosphoamino acid analysis revealed that each of the insulin-responsive phosphoproteins contained phosphoserine as well as phosphotyrosine, though the ratio of two phosphoamino acids recovered from each protein differed. The 61-kDa protein yielded relatively equal proportions of phosphoserine and phosphotyrosine. In contrast, the insulin receptor yielded relatively more label on phosphotyrosine than phosphoserine, whereas label incorporated into the 160-kDa protein was recovered primarily on phosphoserine. Cleveland peptide maps using either Staphylococcus aureus V8 proteinase or chymotrypsin revealed no similarities between the 61-kDa protein and the other tyrosine phosphorylated proteins. With subcellular fractionation, the 160-kDa protein was found in equal proportions in the high speed pellet (100,000 g) and supernatant. The 61-kDa protein had a similar distribution to that of the 160-kDa protein but was also detected in the low speed pellet (10,000 g). The insulin receptor was localized to the low speed pellet. In summary, rat adipocytes contain an insulin-dependent phosphotyrosyl protein of 61 kDa which is distinct from the more prominent high molecular mass receptor substrate. This 61-kDa protein has characteristics consistent with it being a substrate for the insulin receptor tyrosine kinase.

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies.

PubMed

Bergamini, Giorgio; Sigrist, Hannes; Ferger, Boris; Singewald, Nicolas; Seifritz, Erich; Pryce, Christopher R

2016-10-01

Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chronic DA depletion, principally applied in rat to study NAcc DA regulation of reward motivation. Given the increasing focus on studying environmental and genetic regulation of DA function in mouse models, it is important to establish the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion processing. This mouse study investigated effects of 6-OHDA-induced NAcc DA depletion using the operant behavioural test battery of progressive ratio schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill, and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under effortful conditions in the PRS test; to a stimulus recently associated with gustatory non-reward in the LNR test; to escape footshock recently experienced as uncontrollable in the LH test; and to avoid footshock by physical effort in the treadmill test. Evidence for specificity of effects to NAcc DA was provided by lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests. These findings add significantly to the evidence that NAcc DA is a major regulator of behavioural responding, particularly at the motivational level, to both reward and aversion. They demonstrate the suitability of mouse models for translational study of causation and reversal of pathophysiological DA function underlying motivation psychopathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

PubMed

Bruno, J P; Byrnes, E M; Johnson, B J

1995-11-01

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Development and testing of a decision aid for women considering delayed breast reconstruction.

PubMed

Metcalfe, Kelly; Zhong, Toni; O'Neill, Anne C; McCready, David; Chan, Linda; Butler, Kate; Brennenstuhl, Sarah; Hofer, Stefan O P

2018-03-01

The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR. The DA was developed and evaluated in three phases. The first phase included the development of the DA with input and review by practitioners and key stakeholders. The second phase involved pilot testing of the feasibility and acceptability of the DA with a convenience sample of women with delayed PMBR. The third phase involved a pretest/post-test evaluation of the DA for women who were making decisions about their PMBR options. The DA was developed using the Ottawa Decision Support Framework. In the second phase of the study, 21 women completed the acceptability survey, of whom 100% reported that they would recommend the DA to other women. In the third phase, decisional conflict decreased significantly (p < 0.001) and knowledge increased significantly (p < 0.001) from prior to using the DA to 1-2 weeks after using the DA. The DA is feasible and acceptable to women considering delayed PMBR. Furthermore, the DA is effective at reducing decisional conflict and increasing knowledge about delayed PMBR. The DA is an appropriate tool to be used in addition with standard care in women considering PMBR. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

PubMed

Gökce, Mehmet I; Wang, Xuemei; Frost, Jacqueline; Roberson, Pamela; Volk, Robert J; Brooks, Durado; Canfield, Steven E; Pettaway, Curtis A

2017-02-15

The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society. © 2016 American Cancer Society.

High Doses of Amphetamine Augment, Rather Than Disrupt, Exocytotic Dopamine Release in the Dorsal and Ventral Striatum of the Anesthetized Rat

PubMed Central

Ramsson, Eric S.; Howard, Christopher D.; Covey, Dan P.; Garris, Paul A.

2011-01-01

High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action. PMID:21806614

Naval Supply Systems Command: Data Administration Planning and Implementation

DTIC Science & Technology

1989-03-01

determined that management’s lack of understanding is an inhibitor of successful DA. Equally important is the DA group’s comprehension of...is the actual staff responsible for DA. Kahn [Ref. 5] found that an insufficient DA staff was another inhibitor of successful DA implementation. Two...Logistic Network ( NLN ) architecture. 7 3. NAVSUP Strategic Directions Three of NAVSUP’s strategic directions pertain to this study. The first is the

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor microenvironment.« less

The Protective Effect of Pregnancy on Risk for Drug Abuse: A Population, Co-relative, Co-spouse, and Within-Individual Analysis

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Svikis, Dace S.; Sundquist, Kristina; Sundquist, Jan

2017-01-01

Objective To determine whether pregnancy is an intrinsic motivator for drug abuse (DA) cessation. Method We conducted, in Swedish females born 1980–1990 who gave birth at ages 20–35 (N=149,512), prospective cohort, co-relative, co-spouse, and within-person analyses of registration for DA during pregnancy. DA was assessed from medical, criminal and pharmacy registries. Results In the population, rates of DA were lower during pregnancy (unadjusted OR=0.67, 95% CIs 0.60–0.74). Compared to population results, the negative association between pregnancy and DA was moderately stronger in cousins (OR=0.49, 0.39–0.62) and substantially stronger in siblings (OR=0.35, 0.24–0.51) discordant for pregnancy. The estimated OR for DA in pregnancy-discordant monozygotic twins was even stronger: 0.17 (0.10–0.31). Within-individuals, the OR for DA while pregnant compared to an equivalent pre-pregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins: 0.22 (0.19–0.26). Compared to cohabiting fathers, mothers had a greater reduction in risk for DA during pregnancy (OR=0.40, 0.34–0.47). Pregnancy was more protective in those with low parental education and without a cohabiting actively drug abusing father. Compared to pre-pregnancy baseline, within-individual analyses indicate risk for DA is also substantially reduced post-partum e.g. day 0–242 OR=0.13 (0.11–0.16). Conclusions Risk for DA in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for DA cessation. Similar strong protective effects may be present immediately post-partum. Our results have implications for our etiologic models of DA and especially for contingency management programs seeking to reduce DA risk. PMID:28595490

Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations

PubMed Central

Carta, Manolo; Tronci, Elisabetta

2014-01-01

In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson’s disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications. PMID:24904522

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

PubMed

Yucesoy, Berran; Kissling, Grace E; Johnson, Victor J; Lummus, Zana L; Gautrin, Denyse; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Luster, Michael I; Bernstein, David I

2015-12-01

To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

Performances on simulator and da Vinci robot on subjects with and without surgical background.

PubMed

Moglia, Andrea; Ferrari, Vincenzo; Melfi, Franca; Ferrari, Mauro; Mosca, Franco; Cuschieri, Alfred; Morelli, Luca

2017-08-17

To assess whether previous training in surgery influences performance on da Vinci Skills Simulator and da Vinci robot. In this prospective study, thirty-seven participants (11 medical students, 17 residents, and 9 attending surgeons) without previous experience in laparoscopy and robotic surgery performed 26 exercises at da Vinci Skills Simulator. Thirty-five then executed a suture using a da Vinci robot. The overall scores on the exercises at the da Vinci Skills Simulator show a similar performance among the groups with no statistically significant pair-wise differences (p < .05). The quality of the suturing based on the unedited videos of the test run was similar for the intermediate (7 (4, 10)) and expert group (6.5 (4.5, 10)), and poor for the untrained groups (5 (3.5, 9)), without statistically significant difference (p < .05). This study showed, for subjects new to laparoscopy and robotic surgery, insignificant differences in the scores at the da Vinci Skills Simulator and at the da Vinci robot on inanimate models.

( sup 3 H)Dopamine uptake by platelet storage granules in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabey, J.M.; Graff, E.; Oberman, Z.

1992-01-01

({sup 3}H)Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p>0.05). The apparent Michaelis constant (kM) of DA uptake in acute patients was also significantly different from chronic patients a substantial diminution of DA uptake, while haloperidol produced a substantial diminution of DA uptake, while haloperidol (10{sup {minus}4}, 10{sup {minus}5} M) did not affect the assay. Considering that a DA disequilibrium in schizophrenia maymore » be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.« less

Da Vinci robot-assisted system for thymectomy: experience of 55 patients in China.

PubMed

Jun, Yi; Hao, Li; Demin, Li; Guohua, Dong; Hua, Jing; Yi, Shen

2014-09-01

Da Vinci robot-assisted thymectomy has been used in the past several years in China, however, practical experience in performing this approach in China remains limited. Thus, the study aimed to evaluate the experience of da Vinci robot-assisted thymectomy in China. From June 2010 to December 2012, 55 patients with diseases of the thymus underwent thymectomy using the da Vinci surgical HD robotic system. The clinical data of the da Vinci robot-assisted thymectomies were compared with the data of video-assisted thoracoscopic thymectomies in the same period. All da Vinci robot operations were successful. This is a retrospective analysis which demonstrated that compared with video-assisted thoracoscopic thymectomy in the same period, the clinical outcomes of da Vinci robot-assisted thymectomy were not significantly different. The da Vinci robot-assisted thymectomy is a safe, minimally invasive, and convenient operation, and shows promise for general thoracic surgery in China. Copyright © 2014 John Wiley & Sons, Ltd.

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

2015-10-01

Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The results indicate that nepicastat enhances DA release from noradrenergic terminals supposedly by removing NA from α2-autoreceptors. In addition to the inhibition of DA uptake, the latter mechanism may explain the synergistic effect of cocaine on nepicastat-induced DA release.

Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis)

PubMed Central

Xu, Min-jie; Zhang, Cong; Yang, Zhigang

2018-01-01

Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light adaptation and digestive functions of the DA2 receptor in decapods. PMID:29554147

Deciding how many embryos to transfer after in vitro fertilisation: development and pilot test of a decision aid.

PubMed

van Peperstraten, Arno M; Hermens, Rosella P M G; Nelen, Willianne L D M; Stalmeier, Peep F M; Wetzels, Alex M M; Maas, Pettie H M; Kremer, Jan A M; Grol, Richard P T M

2010-01-01

When deciding how many embryos to transfer during in vitro fertilisation (IVF), clinicians and patients have to balance optimizing the chance of pregnancy against preventing multiple pregnancies and the associated complications. This paper describes the development and pilot test of a patient decision aid (DA) for this purpose. The development of the DA consisted of a literature search, establishment of the format, and a pilot test among IVF patients. The DA development was supervised by a panel of experts in the fields of subfertility, obstetrics and DA-research and it was based on the criteria of the International Patient Decision Aid Standards. One Cochrane review and 34 articles were selected for the DA content. The DA presents information in text, summaries, tables, figures and through an interactive worksheet. The DA was reviewed positively and as acceptable for use in clinical practice by patients and professionals. The DA was thoroughly developed and is likely to be helpful for the decision-making process for the number of embryos transferred after IVF. Physicians and researchers can use the DA without restriction in clinical practice or research related to decision-making.

Biosynthesis and intracellular transport of the receptor for platelet-derived growth factor.

PubMed Central

Claesson-Welsh, L; Rönnstrand, L; Heldin, C H

1987-01-01

The biosynthesis of the receptor for platelet-derived growth factor (PDGF) was examined in metabolically labeled human foreskin fibroblasts. The receptor was synthesized as a 145-kDa precursor, which, when incubated with endo-beta-N-acetylglucosaminidase H (endo H), underwent a 15-kDa decrease in molecular mass. This indicates that the size of the core protein is about 130 kDa and that the 145-kDa form represents a receptor precursor carrying high-mannose N-linked oligosaccharide groups. Within 15 min after synthesis, the receptor was converted to a 165-kDa form. This form was entirely resistant to endo H treatment and probably represents a receptor molecule that has undergone further posttranslational modification, including O-linked glycosylation. Subsequently, within 30 min, a molecule of 170 kDa--i.e., the size of the mature receptor--appeared. A slightly larger molecule, of 175 kDa, which could be immunoprecipitated from PDGF-stimulated 32P-labeled cells, probably represents a receptor further modified by autophosphorylation. The 170-kDa molecule had an isoelectric point of about 4.5. Addition of PDGF increased the turnover rate of the 170-kDa PDGF receptor. Images PMID:2827155

Do laparoscopic skills transfer to robotic surgery?

PubMed

Panait, Lucian; Shetty, Shohan; Shewokis, Patricia A; Sanchez, Juan A

2014-03-01

Identifying the set of skills that can transfer from laparoscopic to robotic surgery is an important consideration in designing optimal training curricula. We tested the degree to which laparoscopic skills transfer to a robotic platform. Fourteen medical students and 14 surgery residents with no previous robotic but varying degrees of laparoscopic experience were studied. Three fundamentals of laparoscopic surgery tasks were used on the laparoscopic box trainer and then the da Vinci robot: peg transfer (PT), circle cutting (CC), and intracorporeal suturing (IS). A questionnaire was administered for assessing subjects' comfort level with each task. Standard fundamentals of laparoscopic surgery scoring metric were used and higher scores indicate a superior performance. For the group, PT and CC scores were similar between robotic and laparoscopic modalities (90 versus 90 and 52 versus 47; P > 0.05). However, for the advanced IS task, robotic-IS scores were significantly higher than laparoscopic-IS (80 versus 53; P < 0.001). Subgroup analysis of senior residents revealed a lower robotic-PT score when compared with laparoscopic-PT (92 versus 105; P < 0.05). Scores for CC and IS were similar in this subgroup (64 ± 9 versus 69 ± 15 and 95 ± 3 versus 92 ± 10; P > 0.05). The robot was favored over laparoscopy for all drills (PT, 66.7%; CC, 88.9%; IS, 94.4%). For simple tasks, participants with preexisting skills perform worse with the robot. However, with increasing task difficulty, robotic performance is equal or better than laparoscopy. Laparoscopic skills appear to readily transfer to a robotic platform, and difficult tasks such as IS are actually enhanced, even in subjects naive to the technology. Copyright © 2014 Elsevier Inc. All rights reserved.

New objects with the B[e] phenomenon in the Large Magellanic Cloud

NASA Astrophysics Data System (ADS)

Levato, H.; Miroshnichenko, A. S.; Saffe, C.

2014-08-01

Aims: The study is aimed at discovering new objects with the B[e] phenomenon in the Large Magellanic Cloud. Methods: We report medium-resolution optical spectroscopic observations of two newly found (ARDB 54 and NOMAD 0181-0125572) and two previously known (Hen S-59 and Hen S-137) supergiants with the B[e] phenomenon in the Large Magellanic Cloud. The observations were obtained with the GMOS spectrograph at the southern Gemini telescope. Results: The optical spectra and the fundamental parameters of ARDB 54 and NOMAD 0181-0125572 are presented for the first time. We found that the Balmer line profiles of Hen S-59 and Hen S-137 were different from those observed in their spectra nearly 20 years ago. We suggest a higher effective temperature and luminosity for both objects. With the new fundamental parameters, the lowest luminosity for known supergiants with the B[e] phenomenon in the Magellanic Clouds is higher that previously thought (log L/L⊙ ~ 4.5 instead of 4.0). The object Hen S-59 may be a binary system based on its UV excess, variable B - V color-index and radial velocity of emission lines, and periodically variable I-band brightness. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência, Tecnologia e Inovacão (Brazil) and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina).

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal.

PubMed

Kaufling, Jennifer; Aston-Jones, Gary

2015-07-15

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA-VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA-VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. Copyright © 2015 the authors 0270-6474/15/3510290-14$15.00/0.

Estudo espectral em raios-X duros de fontes do tipo Z com o HEXTE/RXTE

NASA Astrophysics Data System (ADS)

D'Amico, F.; Heindl, W. A.; Rothschild, R. E.

2003-08-01

Apresentam-se os resultados de um estudo espectral em raios-X de fontes do tipo Z. As fontes do tipo Z são binárias de raios-X de baixa massa (BXBM) com campo magnético intermediário (B~109G). Esta classe de fontes é composta por apenas 6 fontes Galácticas (a saber: ScoX-1, 9, 7, CygX-2, 5 e 0). A nossa análise se concentra na faixa de raios-X duros (E ~ 20keV), até cerca de 200keV, faixa ótima de operação do telescópio "High Energy X-ray Timing Experiment" (HEXTE), um dos três telescópios de raios-X à bordo do Rossi X-ray Timing Explorer (RXTE). Nossa motivação para tal estudo, uma busca de caudas em raios-X duros em fontes do tipo Z, foi o pouco conhecimento sobre a emissão nesta faixa de energia das referidas fontes quando comparadas, por exemplo, as fontes do tipo atoll (também BXBM). Apresentam-se a análise/redução de dados e explicita-se a maneira como o HEXTE mede o ru1do de fundo. Especial atenção é direcionada a este item devido a localização das fontes do tipo Z e também ao problema de contaminação por fontes próximas. Com exceção de ScoX-1, nenhuma cauda em raios-X duros foi encontrada para as outras fontes, a despeito de resultados de detecção dessas caudas em algumas fontes pelo satélite BeppoSAX. As interpretações deste resultado serão apresentadas. Do ponto de vista deste estudo, nós deduzimos que a produção de caudas de raios-X duros em fontes do tipo Z é um processo disparado quando, pelo menos, uma condição é satisfeita: o brilho da componente térmica do espectro precisa estar acima de um certo valor limiar de ~4´1036ergs-1.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice.

PubMed

McCall, Nora M; Kotecki, Lydia; Dominguez-Lopez, Sergio; Marron Fernandez de Velasco, Ezequiel; Carlblom, Nicholas; Sharpe, Amanda L; Beckstead, Michael J; Wickman, Kevin

2017-02-01

The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K + (GIRK/Kir3) channels mediate the direct inhibitory effect of GABA B receptor (GABA B R) and D 2 DA receptor (D 2 R) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on D 2 R-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors. Selective ablation of Girk2 in DA neurons did not alter the baseline excitability of VTA DA neurons but significantly reduced the magnitude of D 2 R-dependent inhibitory somatodendritic currents and blunted the impact of D 2 R activation on spontaneous activity and neuronal excitability. Mice lacking GIRK channels in DA neurons exhibited increased locomotor activation in response to acute cocaine administration and an altered locomotor sensitization profile, as well as increased responding for and intake of cocaine in an intravenous self-administration test. These mice, however, showed unaltered cocaine-induced conditioned place preference. Collectively, our data suggest that feedback inhibition to VTA DA neurons, mediated by GIRK channel activation, tempers the locomotor stimulatory effect of cocaine while also modulating the reinforcing effect of cocaine in an operant-based self-administration task.

Enhanced Dopamine Detection Sensitivity by PEDOT/Graphene Oxide Coating on in vivo Carbon Fiber Electrodes

PubMed Central

Taylor, I. Mitch; Robbins, Elaine M.; Catt, Kasey A.; Cody, Patrick A.; Weaver, Cassandra L.; Cui, Xinyan Tracy

2016-01-01

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID:27268013

Evidence for a dopamine intrinsic direct role in the regulation of the ovary reproductive function: in vitro study on rabbit corpora lutea.

PubMed

Parillo, Francesco; Maranesi, Margherita; Mignini, Fiorenzo; Marinelli, Lisa; Di Stefano, Antonio; Boiti, Cristiano; Zerani, Massimo

2014-01-01

Dopamine (DA) receptor (DR) type 1 (D1R) has been found to be expressed in luteal cells of various species, but the intrinsic role of the DA/DRs system on corpora lutea (CL) function is still unclear. Experiments were devised to characterize the expression of DR types and the presence of DA, as well as the in vitro effects of DA on hormone productions by CL in pseudopregnant rabbits. Immunoreactivity and gene expression for D1R decreased while that for D3R increased in luteal and blood vessel cells from early to late pseudopregnant stages. DA immunopositivity was evidenced only in luteal cells. The DA and D1R agonist increased in vitro release of progesterone and prostaglandin E2 (PGE2) by early CL, whereas the DA and D3R agonist decreased progesterone and increased PGF2α in vitro release by mid- and late CL. These results provide evidence that the DA/DR system exerts a dual modulatory function in the lifespan of CL: the DA/D1R is luteotropic while the DA/D3R is luteolytic. The present data shed new light on the physiological mechanisms regulating luteal activity that might improve our ability to optimize reproductive efficiency in mammal species, including humans.

Effectivity of immunostimulant from Zoothamnium penaei protein membrane for decreasing the mortality rate of white shrimp (Litopenaeus vannamei) in traditional plus pond

NASA Astrophysics Data System (ADS)

Mahasri, G.; Kusdarwati, R.; Kismiyati; Rozi; Gustrifandi, H.

2018-04-01

The purpose of this research was to analys immunogenic membrane protein as immunostimulant development material to control the mortality of white shrimp in traditional plus pond. This research was designed to use explorative experiment and experimental laboratory methods which used completed random sampling design. Collected data was analyzed with analysis of variance for examination of survival rate (SR), total haemocyte count (THC) and differensial haemocyte Count (DHC). The research divided into 2 part of riset: (1) Identification, cultivation Zoothamnium penaei, analysed of membrane protein by SDS-PAGE, (2) Field test protein membran on Survival Rate level, immune response (THC and/or DHC level) and infestation of Zoothamnium penaei in traditional plus pond. The result showed that there were seven bands membrane protein of Zoothamnium penaei with molecular weight 38 kDa, 48 kDa, 67 kDa, 71 kDa, 77 kDa, 98 kDa dan 104 kDa by using SDS-PAGE. Immunogenicity tested decrease by using ELISA and western blotting there are only found three bands with molecular weight 38 kDa, 48 kDa dan 67 kDa. The membrane protein could increase the immun respons and decrease the mortality, by subsequenly, it could increase the survival rate from 17% until 68% and pressured the parasite infestation of white shrimp.

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

PubMed

Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

2017-01-01

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

2016-09-01

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.

PubMed

Herrera-Mundo, Nieves; Sitges, María

2013-01-01

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

PubMed

Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

32 CFR 537.16 - Scope for maritime claims.

Code of Federal Regulations, 2010 CFR

2010-07-01

... claims for damage to: (1) DA-accountable properties of a kind that are within the federal maritime jurisdiction. (2) Property under the DA's jurisdiction or DA property damaged by a vessel or floating object... services (including contract salvage and towage) performed by the DA. Claims for salvage services are based...

Xenopus-FV3 host-pathogen interactions and immune evasion.

PubMed

Jacques, Robert; Edholm, Eva-Stina; Jazz, Sanchez; Odalys, Torres-Luquis; Francisco, De Jesús Andino

2017-11-01

We first review fundamental insights into anti-ranavirus immunity learned with the Xenopus laevis/ranavirus FV3 model that are generally applicable to ectothermic vertebrates. We then further investigate FV3 genes involved in immune evasion. Focusing on FV3 knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD)-like protein (Δ64R-FV3), a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3), and an immediate-early18kDa protein (FV3-Δ18K), we assessed the involvement of these viral genes in replication, dissemination and interaction with peritoneal macrophages in tadpole and adult frogs. Our results substantiate the role of 64R and 52L as critical immune evasion genes, promoting persistence and dissemination in the host by counteracting type III IFN in tadpoles and type I IFN in adult frogs. Comparably, the substantial accumulation of genome copy numbers and exacerbation of type I and III IFN gene expression responses but deficient release of infectious virus suggests that 18K is a viral regulatory gene. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Functional diversification and specialization of cytosolic 70-kDa heat shock proteins.

PubMed

McCallister, Chelsea; Siracusa, Matthew C; Shirazi, Farzaneh; Chalkia, Dimitra; Nikolaidis, Nikolas

2015-03-20

A fundamental question in molecular evolution is how protein functional differentiation alters the ability of cells and organisms to cope with stress and survive. To answer this question we used two paralogous Hsp70s from mouse and explored whether these highly similar cytosolic molecular chaperones, which apart their temporal expression have been considered functionally interchangeable, are differentiated with respect to their lipid-binding function. We demonstrate that the two proteins bind to diverse lipids with different affinities and therefore are functionally specialized. The observed lipid-binding patterns may be related with the ability of both Hsp70s to induce cell death by binding to a particular plasma-membrane lipid, and the potential of only one of them to promote cell survival by binding to a specific lysosomal-membrane lipid. These observations reveal that two seemingly identical proteins differentially modulate cellular adaptation and survival by having acquired specialized functions via sequence divergence. Therefore, this study provides an evolutionary paradigm, where promiscuity, specificity, sub- and neo-functionalization orchestrate one of the most conserved systems in nature, the cellular stress-response.

Underwater Inherent Optical Properties Estimation Using a Depth Aided Deep Neural Network.

PubMed

Yu, Zhibin; Wang, Yubo; Zheng, Bing; Zheng, Haiyong; Wang, Nan; Gu, Zhaorui

2017-01-01

Underwater inherent optical properties (IOPs) are the fundamental clues to many research fields such as marine optics, marine biology, and underwater vision. Currently, beam transmissometers and optical sensors are considered as the ideal IOPs measuring methods. But these methods are inflexible and expensive to be deployed. To overcome this problem, we aim to develop a novel measuring method using only a single underwater image with the help of deep artificial neural network. The power of artificial neural network has been proved in image processing and computer vision fields with deep learning technology. However, image-based IOPs estimation is a quite different and challenging task. Unlike the traditional applications such as image classification or localization, IOP estimation looks at the transparency of the water between the camera and the target objects to estimate multiple optical properties simultaneously. In this paper, we propose a novel Depth Aided (DA) deep neural network structure for IOPs estimation based on a single RGB image that is even noisy. The imaging depth information is considered as an aided input to help our model make better decision.

A mathematical model for the thrust force generated by a flapping elastic wing

NASA Astrophysics Data System (ADS)

Tarasov, Alexander E.; Sumbatyan, Mezhlum A.

2012-11-01

The physical nature of the thrust force generated by flapping wings is of a long-time interest of many researchers. The idea of the thrust effect came from the observation of birds' flight. Apparently, Leonardo da Vinci was first who tried to explain the mechanism of the flapping wing trust, for possible engineering applications. Nevertheless, the fundamental basics of a theoretical study of wing oscillations were laid only near the beginning of the 20th century. The thrust effect of the flapping wing was explained by Knoller in 1909 and Betz in 1912, independently. The principal problem in this theory is to define an optimal deformation law which provides the flapping wing to work with highest efficiency. In the present paper we study a rectangular elastic wing of finite span as a propulsion device. We propose an analytical approach, to study harmonic oscillations of a thin elastic rectangular wing at zero attack angle in a flow of inviscid incompressible fluid. The problem is reduced to an integro-differential equation, in frames of the "plane sections" hypothesis.

RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

PubMed

Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

2011-01-05

The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

Comparative study of wine tannin classification using Fourier transform mid-infrared spectrometry and sensory analysis.

PubMed

Fernández, Katherina; Labarca, Ximena; Bordeu, Edmundo; Guesalaga, Andrés; Agosin, Eduardo

2007-11-01

Wine tannins are fundamental to the determination of wine quality. However, the chemical and sensorial analysis of these compounds is not straightforward and a simple and rapid technique is necessary. We analyzed the mid-infrared spectra of white, red, and model wines spiked with known amounts of skin or seed tannins, collected using Fourier transform mid-infrared (FT-MIR) transmission spectroscopy (400-4000 cm(-1)). The spectral data were classified according to their tannin source, skin or seed, and tannin concentration by means of discriminant analysis (DA) and soft independent modeling of class analogy (SIMCA) to obtain a probabilistic classification. Wines were also classified sensorially by a trained panel and compared with FT-MIR. SIMCA models gave the most accurate classification (over 97%) and prediction (over 60%) among the wine samples. The prediction was increased (over 73%) using the leave-one-out cross-validation technique. Sensory classification of the wines was less accurate than that obtained with FT-MIR and SIMCA. Overall, these results show the potential of FT-MIR spectroscopy, in combination with adequate statistical tools, to discriminate wines with different tannin levels.

Robust Induction of DARPP32-Expressing GABAergic Striatal Neurons from Human Pluripotent Stem Cells.

PubMed

Fjodorova, Marija; Li, Meng

2018-01-01

Efficient generation of disease relevant neuronal subtypes from human pluripotent stem cells (PSCs) is fundamental for realizing their promise in disease modeling, pharmaceutical drug screening and cell therapy. Here we describe a step-by-step protocol for directing the differentiation of human embryonic and induced PSCs (hESCs and hiPSCs, respectively) toward medium spiny neurons, the type of cells that are preferentially lost in Huntington's disease patients. This method is based on a novel concept of Activin A-dependent induction of the lateral ganglionic/striatal fate using a simple monolayer culture paradigm under chemically defined conditions. Transplantable medium spiny neuron progenitors amenable for cryopreservation are produced in less than 20 days, which differentiate and mature into a high yield of dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP32) expressing gamma-aminobutyric acid (GABA)-ergic neurons in vitro and in the adult rat brain after transplantation. This method has been validated in multiple hESC and hiPSC lines, and is independent of the regime for PSC maintenance.

Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages

PubMed Central

Krizman, Jennifer; Marian, Viorica; Shook, Anthony; Skoe, Erika; Kraus, Nina

2012-01-01

Bilingualism profoundly affects the brain, yielding functional and structural changes in cortical regions dedicated to language processing and executive function [Crinion J, et al. (2006) Science 312:1537–1540; Kim KHS, et al. (1997) Nature 388:171–174]. Comparatively, musical training, another type of sensory enrichment, translates to expertise in cognitive processing and refined biological processing of sound in both cortical and subcortical structures. Therefore, we asked whether bilingualism can also promote experience-dependent plasticity in subcortical auditory processing. We found that adolescent bilinguals, listening to the speech syllable [da], encoded the stimulus more robustly than age-matched monolinguals. Specifically, bilinguals showed enhanced encoding of the fundamental frequency, a feature known to underlie pitch perception and grouping of auditory objects. This enhancement was associated with executive function advantages. Thus, through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound. This study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. PMID:22547804

Evolution of the Astronomy Concepts Along Basic Education Cycle. (Breton Title: Evolução dos Conceitos de Astronomia no Decorrer da Educação Básica.) La Evolución de los Conceptos de Astronomía Durante la Educación Básica

NASA Astrophysics Data System (ADS)

Darroz, Luiz Marcelo; da Rosa, Cleci Werner; Becker da Rosa, Álvaro; Samudio Pèrez, Carlos Ariel

2014-07-01

Although astronomy is considered one of the older sciences of humanity and that the understanding of its concepts has brought tremendous advances to Science and therefore, to society, it is observed that a significant portion of people live outside of this kind of knowledge. According to the Parâmetros Curriculares Nacionais for basic education, it is the school responsibility the dissemination of scientifically correct concepts, including those related to astronomy. Concerning this issue, we present a survey of 140 students of ninth grade of elementary school and 120 third-grade high-school students from four schools in the region of Passo Fundo/RS. We sought to determine, through a questionnaire consisting of open and multiple choice questions, the knowledge of this group of students about the basic terms and astronomical phenomena, and also verify that the hit rate increases as they advance through the different and progressive grades of primary and secondary education. Overall, the results show that the teaching of astronomy in basic education is facing problems. Of the 20 issues investigated, in 17 the indicators are similar in the correct answers given by students for elementary and middle school, revealing that many misconceptions still remain along basic education. This demonstrates that such issues are not - or are rarely - covered during these two school levels. Thus, we conclude that the discussion of concepts related to astronomy should receive greater emphasis on approaching different subjects, requiring a national action in support of their teaching. It is believed that a national action should be supported by a triple pillar of collective actors: the scientific community, semi-professional astronomy community and the school community. Finally, this pillar would be the basis for future discussions related to the performance of these protagonists as a means to promote active changes in the curricular structure, providing, in more effective ways, the learning of astronomy in basic education. Embora a astronomia seja considerada uma das ciências mais antigas da humanidade e ainda que a compreensão de seus conceitos tenha trazido enormes avanços para a Ciência e, consequentemente, para a sociedade, observa-se que uma parcela significativa de pessoas encontra-se à margem desses conhecimentos. De acordo com os Parâmetros Curriculares Nacionais para a Educação Básica, cabe à escola a difusão dos conceitos cientificamente corretos, entre eles os relacionados à área de astronomia. Pertinente a essa questão, apresenta-se uma pesquisa realizada com 140 estudantes do nono ano do ensino fundamental e com 120 estudantes da terceira série do ensino médio de quatro escolas da região de Passo Fundo/RS. Buscou-se averiguar, por meio de um questionário composto de questões abertas e de múltipla escolha, o conhecimento desse grupo de estudantes acerca de termos e fenômenos astronômicos básicos e, também, verificar se o índice de acertos cresce à medida que eles avançam nas diferentes e gradativas séries dos ensinos fundamental e médio. De modo geral, os resultados apresentados demonstram que o ensino de astronomia na educação básica enfrenta deficiências. Das 20 questões investigadas, em 17 os índices de acertos são semelhantes nas respostas dadas por estudantes de nível fundamental e médio, revelando que muitas concepções equivocadas permanecem ao longo da educação básica. Isso evidencia que tais temas não são - ou são pouco - abordados durante esses dois níveis de escolarização. Assim, conclui-se que a discussão dos conceitos relacionados com a astronomia deve receber maior ênfase na abordagem dos diferentes conteúdos, sendo necessária uma ação nacional em prol do seu ensino. Acredita-se que essa ação nacional deve estar apoiada em um pilar triplo de atores coletivos: comunidade científica, comunidade astronômica semiprofissional e comunidade escolar. Por fim, esse pilar seria a base para futuras discussões relacionadas à atuação dessas instâncias como meio de promover mudanças ativistas na estrutura curricular, proporcionando, mais efetivamente, a educação em astronomia no ensino básico. Si bien la astronomía es considerada una de las ciencias más antiguas de la humanidad y aunque la comprensión de sus conceptos haya traído enormes avances para la ciencia y, consecuentemente, para la sociedad, se observa que una parte significativa de personas se encuentran al margen de estos conocimientos. De acuerdo con los Parámetros Curriculares Nacionales para la Educación Básica, corresponde a la escuela la difusión de los conceptos científicamente correctos, entre ellos los relacionados al área de astronomía. Sobre esta cuestión, se presenta una investigación realizada con 140 estudiantes del noveno año de la enseñanza fundamental y con 120 estudiantes del tercer año de la enseñanza de nivel medio de cuatro escuelas de la región de Passo Fundo/RS. Se pretendía averiguar, por medio de un cuestionario compuesto de preguntas abiertas y de opción múltiple, el conocimiento de este grupo de alumnos sobre términos y fenómenos astronómicos básicos y, también, si el índice de aciertos crece en la medida que los alumnos avanzan a los diferentes y sucesivos años de la enseñanza fundamental y media. De modo general, los resultados demuestran que la enseñanza de astronomía en la educación básica muestra deficiencias. De los 20 asuntos investigados, 17 revelan índices de aciertos semejantes en las respuestas dadas por los estudiantes de nivel básico y medio, mostrando que muchas concepciones equivocadas permanecen a lo largo de la educación básica. Esto hace evidente que estos temas no son - o son poco - abordados durante esos niveles de escolarización. Así, puede concluirse que la discusión de los conceptos relacionados a la astronomía debe recibir un mayor énfasis en cuanto al abordaje de los diferentes contenidos, siendo necesaria una acción nacional en pro de su enseñanza. Es necesario destacar que esa acción nacional debe estar apoyada en un pilar triple de actores colectivos: comunidad científica, comunidad de astronomía semi profesional y la comunidad escolar. En fin, ese pilar sería la base para futuras discusiones relacionadas a la actuación de esas instancias como vía para promover cambios en la estructura curricular, proporcionando más efectivamente, la educación en astronomía en la enseñanza de nivel básico.

Setting health priorities in a community: a case example.

PubMed

Sousa, Fábio Alexandre Melo do Rego; Goulart, Maria José Garcia; Braga, Antonieta Manuela Dos Santos; Medeiros, Clara Maria Oliveira; Rego, Débora Cristina Martins; Vieira, Flávio Garcia; Pereira, Helder José Alves da Rocha; Tavares, Helena Margarida Correia Vicente; Loura, Marta Maria Puim

2017-03-02

To describe the methodology used in the process of setting health priorities for community intervention in a community of older adults. Based on the results of a health diagnosis related to active aging, a prioritization process was conceived to select the priority intervention problem. The process comprised four successive phases of problem analysis and classification: (1) grouping by level of similarity, (2) classification according to epidemiological criteria, (3) ordering by experts, and (4) application of the Hanlon method. These stages combined, in an integrated manner, the views of health team professionals, community nursing and gerontology experts, and the actual community. The first stage grouped the identified problems by level of similarity, comprising a body of 19 issues for analysis. In the second stage these problems were classified by the health team members by epidemiological criteria (size, vulnerability, and transcendence). The nine most relevant problems resulting from the second stage of the process were submitted to expert analysis and the five most pertinent problems were selected. The last step identified the priority issue for intervention in this specific community with the participation of formal and informal community leaders: Low Social Interaction in Community Participation. The prioritization process is a key step in health planning, enabling the identification of priority problems to intervene in a given community at a given time. There are no default formulas for selecting priority issues. It is up to each community intervention team to define its own process with different methods/techniques that allow the identification of and intervention in needs classified as priority by the community. Descrever a metodologia utilizada no processo de estabelecimento de prioridades em saúde para intervenção comunitária, numa comunidade idosa. Partindo dos resultados de um diagnóstico de saúde no âmbito da promoção do envelhecimento ativo, concebeu-se um processo de estabelecimento de prioridades a fim de selecionar o problema prioritário para intervenção. O processo integrou quatro etapas sucessivas de análise e classificação dos problemas: (1) agrupamento por nível de similitude, (2) classificação de acordo com critérios epidemiológicos, (3) ordenação por peritos e (4) aplicação do método de Hanlon. No decurso destas etapas, combinaram-se, de forma integrada, as perspetivas dos profissionais da equipe de saúde, de peritos em enfermagem comunitária e gerontologia e da própria comunidade. Na primeira etapa, agruparam-se por nível de similitude os problemas identificados, constituindo-se um corpo de 19 problemas para análise. Na segunda, esses problemas foram classificados pelos elementos da equipe de saúde, mediante a aplicação de critérios de cariz epidemiológico (magnitude, vulnerabilidade e transcendência). Os nove problemas mais relevantes resultantes da operacionalização da segunda etapa do processo foram submetidos a análise por peritos, e selecionados os cinco problemas com maior pertinência de atuação. Na última etapa, com recurso à participação de líderes formais e informais da comunidade, identificou-se o problema prioritário para intervenção nessa comunidade específica: a Baixa Interação Social na Participação Comunitária. O processo de estabelecimento de prioridades é uma etapa fundamental do planejamento em saúde, permitindo identificar os problemas prioritários a intervir numa determinada comunidade e num determinado momento. Não existem fórmulas predeterminadas para a seleção de problemas prioritários. Cabe a cada equipe de intervenção comunitária a definição de um processo próprio com diferentes métodos/técnicas que possibilitem a identificação e intervenção em necessidades classificadas como prioritárias pela comunidade.

Astronomy, Art and Mythology in a Public Elementary School in Itaocara/rj. (Spanish Title: Astronomía, Arte y Mitologia en el Ensino Fundamental en Una Escuela de la Red Estatal en ITAOCARA/RJ.) Astronomia, Arte e Mitologia no Ensino Fundamental em Escola da Rede Estadual em ITAOCARA/RJ

NASA Astrophysics Data System (ADS)

Oliveira Bernardes, Adriana; Ramos dos Santos, Arleidimar

2008-12-01

Volunteer advisors at Itaocara Astronomy Club Marcos Pontes(CAIMP), in their majority high school students, introduced students at Teotônio Brandão Vilela Elementary School to basic concepts in Astronomy, Physics, and Mythology. Computer Science, Arts, puppetry, and educational videos were used to stimulate students to share their feelings and test their knowledge of the concepts presented. The work done by the volunteers helped boost the student's self-esteem and improved their oral skills by applying their knowledge of Physics and Astronomy in Lab experiments. The main goals of the CAIMP are the possibility of including astronomy in Elementary school curricula and developing an interdisciplinary work involving Astronomy, Arts, and Mythology. Through tests and reports, the students who participated in the Brazilian Astronomy Olympics, showed an increase in their knowldge of the sujects presented during the volunteer work. Durante el curso de un trabajo voluntario con estudiantes de nivel primario (1 º a 4 º grado), los guías de Astronomía miembros del CAIMP (Club de Astronomía de Itaocara "Marcos Puentes"), en su mayoría estudiantes secundarios, desarrollaron un trabajo de introducción a las Ciencias y Astronomía con alumnos del colegio estatal Teotônio Vilela Brandão. A través de talleres de informática, artes, videos educativos y teatro de títeres, los estudiantes pudieron expresar sus conocimientos y emociones frente a las leyendas mitológicas con las que se inició el trabajo de introducción. La labor desarrollada por los guías con los alumnos promovió la integración entre las aulas del colegio haciéndolos participar en actividades con el fin de estimular su expresión verbal y aumentar su autoestima. Trabajando diversas formas de expresión, los alumnos pudieron realizar experimentos y conocer algunos conceptos de Física y Astronomía al mismo tiempo que adquirían autonomía para la libre expresión de sus sentimientos y de los conocimientos recibidos. El trabajo en sí ha mostrado además de la posibilidad de la inclusión de la Astronomía en la Educación Primaria, la posibilidad de un trabajo interdisciplinario en los niveles iniciales incluyendo Astronomía, Arte y Mitología. Los resultados presentados por los estudiantes en las Olimpiadas promovidas en la escuela y por la OBA (Olimpiada Brasilera de Astronomía) permitieron verificar un creciente aprendizaje y estimulo hacia las materias científicas, comprobados por la apropiada expresión de los conceptos adquiridos de astronomía y presentados en evaluaciones o en informes obtenidos de ellos mismos, sus familias y profesores. Desenvolvendo um trabalho voluntário junto aos alunos do ensino fundamental no 1º ciclo (1ª a 4ª série), os monitores de Astronomia membros do CAIMP (Clube de Astronomia de Itaocara Marcos Pontes), que eram em sua maioria alunos do ensino médio, desenvolveram um trabalho de aproximação entre os alunos do Colégio Estadual Teotônio Brandão Vilela e os temas envolvendo Ciências e Astronomia. Através de oficinas de informática, artes, vídeos educativos e teatros de fantoches, os alunos puderam expressar seus conhecimentos e emoções diante das lendas mitológicas com as quais começaram a ter contato. O trabalho desenvolvido pelos monitores junto aos alunos proporcionou a integração entre as turmas do colégio e os levou a participação em atividades de maneira a estimular sua oralidade e aumentar sua auto-estima. Trabalhando várias formas de expressões, os alunos puderam realizar seus experimentos e conhecer alguns conceitos de Física e Astronomia, enquanto adquiriam autonomia para se expressarem de acordo com seus sentimentos e conhecimentos adquiridos. O trabalho em si mostrou além da possibilidade de inserção de Astronomia no Ensino Fundamental, a possibilidade de realização de um trabalho interdisciplinar nas séries iniciais envolvendo Astronomia, Arte e Mitologia. Os resultados apresentados pelos alunos nas Olimpíadas promovidas na escola e pela OBA (Olimpíada Brasileira de Astronomia) possibilitaram a verificação de uma crescente aprendizagem e estímulo ao conhecimento de temas científicos, que foi comprovado diante da apropriação dos conceitos de Astronomia adquiridos e apresentados em resultados como avaliações, ou ainda, diante dos relatos obtidos dos mesmos, suas famílias e professores.

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Immunoblot patterns of Taenia asiatica taeniasis.

PubMed

Jeon, Hyeong-Kyu; Eom, Keeseon S

2009-03-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica.

Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda)

PubMed Central

Choi, Min-Ho; Ryu, Jin-Sook; Lee, Mejeong; Li, Shunyu; Chung, Byung-Suk; Chai, Jong-Yil; Sithithaworn, Paiboon; Tesana, Smarn

2003-01-01

The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection. PMID:12972729

Immunoblot Patterns of Taenia asiatica Taeniasis

PubMed Central

Jeon, Hyeong-Kyu

2009-01-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica. PMID:19290097

Dopamine in Drosophila: setting arousal thresholds in a miniature brain

PubMed Central

Van Swinderen, Bruno; Andretic, Rozi

2011-01-01

In mammals, the neurotransmitter dopamine (DA) modulates a variety of behaviours, although DA function is mostly associated with motor control and reward. In insects such as the fruitfly, Drosophila melanogaster, DA also modulates a wide array of behaviours, ranging from sleep and locomotion to courtship and learning. How can a single molecule play so many different roles? Adaptive changes within the DA system, anatomical specificity of action and effects on a variety of behaviours highlight the remarkable versatility of this neurotransmitter. Recent genetic and pharmacological manipulations of DA signalling in Drosophila have launched a surfeit of stories—each arguing for modulation of some aspect of the fly's waking (and sleeping) life. Although these stories often seem distinct and unrelated, there are some unifying themes underlying DA function and arousal states in this insect model. One of the central roles played by DA may involve perceptual suppression, a necessary component of both sleep and selective attention. PMID:21208962

Dopamine Receptors and Parkinson's Disease

PubMed Central

Hisahara, Shin; Shimohama, Shun

2011-01-01

Parkinson's disease (PD) is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa) significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS). In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist. PMID:25954517

Using Dynamic Assessment to Evaluate the Expressive Syntax of Children who use Augmentative and Alternative Communication

PubMed Central

King, Marika R.; Binger, Cathy; Kent-Walsh, Jennifer

2015-01-01

The developmental readiness of four 5-year-old children to produce basic sentences using graphic symbols on an augmentative and alternative communication (AAC) device during a dynamic assessment (DA) task was examined. Additionally, the ability of the DA task to predict performance on a subsequent experimental task was evaluated. A graduated prompting framework was used during DA. Measures included amount of support required to produce the targets, modifiability (change in participant performance) within a DA session, and predictive validity of DA. Participants accurately produced target structures with varying amounts of support. Modifiability within DA sessions was evident for some participants, and partial support was provided for the measures of predictive validity. These initial results indicate that DA may be a viable way to measure young children’s developmental readiness to learn how to sequence simple, rule-based messages via aided AAC. PMID:25621928

Dopamine modulates hemocyte phagocytosis via a D1-like receptor in the rice stem borer, Chilo suppressalis

USDA-ARS?s Scientific Manuscript database

Dopamine (DA) is a signal moiety bridging the nervous and immune systems. DA dysregulation is linked to serious human diseases, including addiction, schizophrenia, and Parkinson's disease. However, DA actions in the immune system remain incompletely understood. In this study, we found that DA modula...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

32 CFR 635.13 - Amendment of records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... delegable. If the decision is made to amend an MPR, a supplemental DA Form 3975 will be prepared. The supplemental DA Form 3975 will change information on the original DA Form 3975 and will be mailed to the... file the supplemental DA Form 3975 with the original MPR and notify the requestor of the amendment of...

32 CFR 536.119 - Scope for maritime claims.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vessel of, or in the service of, the Department of the Army (DA) or by other property under the jurisdiction of the DA. (b) Compensation for towage and salvage service, including contract salvage, rendered to a vessel of, or in the service of, the DA or other property under the jurisdiction of the DA. (c...

76 FR 31457 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation... reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance... DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance. Depending on...

76 FR 14346 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... been reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard... condition for the specified products. The MCAI states: Cracks have been reportedly found on DA 42 Main...

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Discourse analysis: A useful methodology for health-care system researches

PubMed Central

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system. PMID:29296612

Discourse analysis: A useful methodology for health-care system researches.

PubMed

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system.

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin

PubMed Central

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-01-01

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition. PMID:28467382

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin.

PubMed

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-05-03

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition.

Soybean P34 Probable Thiol Protease Probably Has Proteolytic Activity on Oleosins.

PubMed

Zhao, Luping; Kong, Xiangzhen; Zhang, Caimeng; Hua, Yufei; Chen, Yeming

2017-07-19

P34 probable thiol protease (P34) and Gly m Bd 30K (30K) show high relationship with the protease of 24 kDa oleosin of soybean oil bodies. In this study, 9 day germinated soybean was used to separate bioprocessed P34 (P32) from bioprocessed 30K (28K). Interestingly, P32 existed as dimer, whereas 28K existed as monomer; a P32-rich sample had proteolytic activity and high cleavage site specificity (Lys-Thr of 24 kDa oleosin), whereas a 28K-rich sample showed low proteolytic activity; the P32-rich sample contained one thiol protease. After mixing with purified oil bodies, all P32 dimers were dissociated and bound to 24 kDa oleosins to form P32-24 kDa oleosin complexes. By incubation, 24 kDa oleosin was preferentially hydrolyzed, and two hydrolyzed products (HPs; 17 and 7 kDa) were confirmed. After most of 24 kDa oleosin was hydrolyzed, some P32 existed as dimer, and the other as P32-17 kDa HP. It was suggested that P32 was the protease.

The butter flavorant, diacetyl, exacerbates β-amyloid cytotoxicity.

PubMed

More, Swati S; Vartak, Ashish P; Vince, Robert

2012-10-15

Diacetyl (DA), an ubiquitous butter-flavoring agent, was found to influence several aspects of amyloid-β (Aβ) aggregation--one of the two primary pathologies associated with Alzheimer's disease. Thioflavin T fluorescence and circular dichroism spectroscopic measurements revealed that DA accelerates Aβ¹⁻⁴² aggregation into soluble and ultimately insoluble β-pleated sheet structures. DA was found to covalently bind to Arg⁵ of Aβ¹⁻⁴² through proteolytic digestion-mass spectrometric experiments. These biophysical and chemical effects translated into the potentiation of Aβ¹⁻⁴² cytotoxicity by DA toward SH-SY5Y cells in culture. DA easily traversed through a MDR1-MDCK cell monolayer, an in vitro model of the blood-brain barrier. Additionally, DA was found not only to be resistant to but also inhibitory toward glyoxalase I, the primary initiator of detoxification of amyloid-promoting reactive dicarbonyl species that are generated naturally in large amounts by neuronal tissue. In light of the chronic exposure of industry workers to DA, this study raises the troubling possibility of long-term neurological toxicity mediated by DA.

Fluorescent light induces neurodegeneration in the rodent nigrostriatal system but near infrared LED light does not.

PubMed

Romeo, Stefania; Vitale, Flora; Viaggi, Cristina; di Marco, Stefano; Aloisi, Gabriella; Fasciani, Irene; Pardini, Carla; Pietrantoni, Ilaria; Di Paolo, Mattia; Riccitelli, Serena; Maccarone, Rita; Mattei, Claudia; Capannolo, Marta; Rossi, Mario; Capozzo, Annamaria; Corsini, Giovanni U; Scarnati, Eugenio; Lozzi, Luca; Vaglini, Francesca; Maggio, Roberto

2017-05-01

We investigated the effects of continuous artificial light exposure on the mouse substantia nigra (SN). A three month exposure of C57Bl/6J mice to white fluorescent light induced a 30% reduction in dopamine (DA) neurons in SN compared to controls, accompanied by a decrease of DA and its metabolites in the striatum. After six months of exposure, neurodegeneration progressed slightly, but the level of DA returned to the basal level, while the metabolites increased with respect to the control. Three month exposure to near infrared LED light (∼710nm) did not alter DA neurons in SN, nor did it decrease DA and its metabolites in the striatum. Furthermore mesencephalic cell viability, as tested by [ 3 H]DA uptake, did not change. Finally, we observed that 710nm LED light, locally conveyed in the rat SN, could modulate the firing activity of extracellular-recorded DA neurons. These data suggest that light can be detrimental or beneficial to DA neurons in SN, depending on the source and wavelength. Copyright © 2017 Elsevier B.V. All rights reserved.

Different protein profile in amniotic fluid with nervous system malformations by surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

PubMed

Ma, Zhe; Liu, Cun; Deng, Biping; Dong, Shaogang; Tao, Guowei; Zhan, Xinfeng; Wang, Chuner; Liu, Shaoping; Qu, Xun

2010-12-01

To detect the distinct proteins in amniotic fluid (AF) between nervous system malformations fetuses and normal fetuses. Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry was used to characterize AF peptides in AF between nervous system malformations fetuses and normal fetuses. WCX2 protein chips were used to characterize AF peptides in AF. Protein chips were examined in a PBSIIC protein reader, the protein profiling was collected by ProteinChip software version 3.1 (Ciphergen Biosystems, Fremont, CA, USA) and analyzed by Biomarker Wizard software (Ciphergen Biosystems). Nine distinct proteins were identified in AF between nervous system malformations fetuses and normal fetuses. Compared with the control group, three proteins with m/z 4967.5 Da, 5258.0 Da, and 11,717.0 Da were down-regulated, and six proteins with m/z 2540.4 Da, 3107.1 Da, 3396.8 Da, 4590.965 Da, 5589.2 Da and 6429.4 Da up-regulated in nervous system malformations fetuses. The results suggest that there are distinct proteins in protein profiling of AF between nervous system malformations fetuses and normal fetuses. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Dopamine Receptors and Neurodegeneration

PubMed Central

Rangel-Barajas, Claudia; Coronel, Israel; Florán, Benjamín

2015-01-01

Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases. PMID:26425390

Amphetamine Augments Action Potential-Dependent Dopaminergic Signaling in the Striatum in Vivo

PubMed Central

Ramsson, Eric S.; Covey, Daniel P.; Daberkow, David P.; Litherland, Melissa T.; Juliano, Steven A.; Garris, Paul A.

2011-01-01

Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine Km and Vmax for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH. PMID:21443523

Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases

NASA Technical Reports Server (NTRS)

Roswit, W. T.; McCourt, D. W.; Partridge, N. C.; Jeffrey, J. J.

1992-01-01

Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin-Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels.

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

A monoclonal antibody that distinguishes latent and active forms of the proteasome (multicatalytic proteinase complex)

NASA Technical Reports Server (NTRS)

Weitman, D.; Etlinger, J. D.

1992-01-01

Monoclonal antibodies (mAbs) were generated to proteasome purified from human erythrocytes. Five of six proteasome-specific mAbs reacted with three subunits in the molecular mass range of 25-28 kDa, indicating a common epitope. The other mAb (AP5C10) exhibited a more restricted reactivity, recognizing a 32-kDa subunit of the proteasome purified in its latent state. However, when the proteasome is isolated in its active state, AP5C10 reacts with a 28-kDa subunit, evidence for processing of the proteasome subunits during purification. Purified proteasome preparations which exhibited partial latency have both AP5C10 reactive subunits. Although the 32-kDa subunit appears required for latency, loss of this component and generation of the 28-kDa component are not obligatory for activation. The 32- and 28-kDa subunits can each be further resolved into three components by isoelectric focusing. The apparent loss of 4 kDa during the conversion of the 32- to 28-kDa subunit is accompanied by a shift to a more basic pI for each polypeptide. Western blots of the early steps of proteasome purification reveal an AP5C10-reactive protein at 41 kDa. This protein was separated from proteasomes by sizing chromatography and may represent a pool of precursor subunits. Since the 32-kDa subunit appears necessary for latency, it is speculated to play a regulatory role in ATP-dependent proteolytic activity.

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

PubMed

Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

1996-04-01

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Impact of a web-based prostate cancer treatment decision aid on patient-reported decision process parameters: results from the Prostate Cancer Patient Centered Care trial.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Kil, Paul J M; van de Poll-Franse, Lonneke V; de Vries, Marieke

2018-05-12

To compare patients' evaluation of the treatment decision-making process in localized prostate cancer between counseling that included an online decision aid (DA) and standard counseling. Eighteen Dutch hospitals were randomized to DA counseling (n = 235) or the control group with standard counseling (n = 101) in a pragmatic, cluster randomized controlled trial. The DA was provided to patients at, or soon after diagnosis. Decisional conflict, involvement, knowledge, and satisfaction with information were assessed with a questionnaire after treatment decision-making. Anxiety and depression served as covariates. The levels of decision involvement and conflict were comparable between patients in both groups. Patients with a DA felt more knowledgeable but scored equally well on a knowledge test as patients without a DA. Small significant negative effects were found on satisfaction with information and preparation for decision-making. A preference for print over online and depression and anxiety symptoms was negatively associated with satisfaction and conflict scores in the DA group. The DA aimed to support shared decision-making, while outcomes for a majority of DA users were comparable to patients who received standard counseling. Patients, who are less comfortable with the online DA format or experience anxiety or depression symptoms, could require more guidance toward shared decision-making. To evaluate long-term DA effects, follow-up evaluation on treatment satisfaction and decisional regret will be done.

Electrochemical Detection of Dopamine via Assisted Ion Transfer at Nanopipet Electrode Using Cyclic Voltammetry.

PubMed

Colombo, Michelle L; McNeil, Swami; Iwai, Nicholas; Chang, Albert; Shen, Mei

2016-01-01

We present here the detection of dopamine (DA) at nanopipet electrodes with radii of hundreds of nanometers ranging from 160 nm to 480 nm. Dibenzo-18-crown-6 (DB18C6) was employed as an ionophore to facilitate DA transfer, resulting in a half-wave transfer potential, E 1/2, DA , of -0.322 (±0.020) V vs. E 1/2, TBA . Well-defined steady-state sigmoidal cyclic voltammograms were observed for the transfer of DA. High resolution scanning electron microscopy was used to measure the size and taper angle of the nanopipet electrodes. The detection is linear with concentration of DA ranging from 0.25 mM to 2 mM; calculated diffusion coefficient at nanopipet electrodes with above mentioned sizes is 4.87 (±0.28) × 10 -10 m 2 /s. The effect of the common interferent ascorbic acid on DA detection with nanopipet electrodes was evaluated, where DA detection still shows linear behavior with well-defined sigmoidal CVs with E 1/2, DA being -0.328 (±0.029) V vs. E 1/2, TBA . The diffusion coefficient for DA transfer in MgCl 2 with the presence of 2 mM AA was measured to be 1.93 (±0.59) × 10 -10 m 2 /s on nanoelectrodes with radii from 161 nm to 263 nm, but the physiological concentration of 0.1 mM AA had no effect on DA's diffusion coefficient.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons

PubMed Central

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C.; Bunney, Benjamin S.; Peterson, Bradley S.

2012-01-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. PMID:22831464

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Influence of Culture Conditions on Expression of the 40-Kilodalton Porin Protein of Vibrio anguillarum Serotype O2

PubMed Central

Davey, Michelle L.; Hancock, Robert E. W.; Mutharia, Lucy M.

1998-01-01

Vibrio anguillarum serotype O2 strains express a 40-kDa outer membrane porin protein. Immunoblot analysis revealed that antigenic determinants of the V. anguillarum O2 40-kDa porin were conserved within bacterial species of the genus Vibrio. The relative amounts of the V. anguillarum O2 40-kDa porin were enhanced by growth of V. anguillarum O2 in CM9 medium containing 5 to 10% sucrose or 0.1 to 0.5 M NaCl. In contrast, the levels of the porin were significantly reduced when cells were grown at 37°C, and a novel 60-kDa protein was also observed. However, the osmolarity or ionic concentration of the growth medium did not influence expression of the 60-kDa protein. Growth in medium containing greater than 0.6 mM EDTA reduced production of the V. anguillarum O2 40-kDa porin and enhanced levels of a novel 19-kDa protein. Thus, expression of the V. anguillarum O2 40-kDa porin was osmoregulated and possibly coregulated by temperature. The N-terminal amino acid sequence of the V. anguillarum O2 40-kDa protein and the effect of environmental factors on the cellular levels of the porin suggested that the V. anguillarum O2 40-kDa porin was functionally similar to the OmpC porin of Escherichia coli. However, pore conductance assays revealed that the V. anguillarum O2 40-kDa porin was a general diffusion porin with a pore size in the range of that of the OmpF porin of E. coli. PMID:9435071

Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

PubMed Central

Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

2015-01-01

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

Redox changes accompanying storage protein mobilization in moist chilled and warm incubated walnut kernels prior to germination.

PubMed

Shahmoradi, Zeynab; Tamaskani, Fatemeh; Sadeghipour, Hamid Reza; Abdolzadeh, Ahmad

2013-01-01

Alterations in the redox state of storage proteins and the associated proteolytic processes were investigated in moist-chilled and warm-incubated walnut (Juglans regia L.) kernels prior to germination. The kernel total protein labeling with a thiol-specific fluorochrome i.e. monobromobimane (mBBr) revealed more reduction of 29-32 kDa putative glutelins, while in the soluble proteins, both putative glutelins and 41, 55 and 58 kDa globulins contained reduced disulfide bonds during mobilization. Thus, the in vivo more reduced disulfide bonds of storage proteins corresponds to greater solubility. After the in vitro reduction of walnut kernel proteins pre-treated by N-ethyl maleimide (NEM) with dithioerythrethiol (DTT) and bacterial thioredoxin, the 58 kDa putative globulin and a 6 kDa putative albumin were identified as disulfide proteins. Thioredoxin stimulated the reduction of the H(2)O(2)-oxidized 6 kDa polypeptide, but not the 58 kDa polypeptide by DTT. The solubility of 6 kDa putative albumin, 58 and 19-24 kDa putative globulins and glutelins, respectively, were increased by DTT. The in vitro specific mobilization of the 58 kDa polypeptide that occurred at pH 5.0 by the kernel endogenous protease was sensitive to the serine-protease inhibitor phenylmethylsulfonyl fluoride (PMSF) and stimulated by DTT. The specific degradation of the 58 kDa polypeptide might be achieved through thioredoxin-mediated activation of a serine protease and/or reductive unfolding of its 58 kDa polypeptide substrate. As redox changes in storage proteins occurred equally in both moist chilled and warm incubated walnut kernels, the regulatory functions of thioredoxins in promoting seed germination may be due to other germination related processes. Copyright © 2012 Elsevier GmbH. All rights reserved.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Chemopreventive effects of Korean Angelica vs. its major pyranocoumarins on two lineages of transgenic adenocarcinoma of mouse prostate carcinogenesis

PubMed Central

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-01-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Since decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage-treated daily with excipient vehicle, AGN (5 mg per mouse) or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA and their common metabolite decursinol indicated similar retention from AGN vs. D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN-and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN-and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal-transition, invasion-metastasis and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. PMID:26116406

Chemopreventive Effects of Korean Angelica versus Its Major Pyranocoumarins on Two Lineages of Transgenic Adenocarcinoma of Mouse Prostate Carcinogenesis.

PubMed

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-09-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal transition, invasion-metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. ©2015 American Association for Cancer Research.

The causes of parent–offspring transmission of drug abuse: a Swedish population-based study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. Method We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n=2111074), ‘not-lived-with’ (n = 165315, where biological parents never lived with their offspring) and ‘step’ (n = 124800 offspring)], which reflected, respectively, the effects of genes+rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Results Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in ‘not-lived-with’ and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than ‘not-lived-with’ child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Conclusions Both genetic and environmental factors contribute substantially to parent–offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent–offspring resemblance. PMID:25066684

Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity.

PubMed

Wu, Jin; Zhang, Ruihua; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Chen, Kang; Cai, Wei

2015-01-01

MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-γ production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-γ-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy. © Society for Leukocyte Biology.

Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

PubMed

Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

2014-09-01

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

PubMed Central

Martin, H.L.; Alsaady, I.; Howell, G.; Prandovszky, E.; Peers, C.; Robinson, P.; McConkey, G.A.

2015-01-01

Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine (DA) in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced DA were not defined. In order to clarify the effects of infection on host DA biosynthetic enzymes and DA packaging we examined enzyme levels and activity and DA accumulation and release in T. gondii-infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH) and DOPA decarboxylase and AADC (DDC) did not change significantly in infected cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DDC was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of DA within tissue cysts in infected brain as a parasite-encoded enzyme with TH activity was also localized within tissue cysts. In contrast, cellular DA packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased DA was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated DA within dopaminergic cells without the toxic ramifications of free cytosolic DA. The mechanism for synthesis and packaging of DA by T. gondii-infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals. PMID:26297895

Dysfunctions in Dopamine Systems and ADHD: Evidence From Animals and Modeling

PubMed Central

Viggiano, Davide; Vallone, Daniela; Sadile, Adolfo

2004-01-01

Animal models are useful for characterizing neural substrates of neuropsychiatric disorders. Several models have been proposed for the study of Attention Deficit Hyperactivity Disorder (ADHD). The models can be divided into various groups: (i) genetically derived hyperactivity/ inattention, (ii) animal models showing symptoms after pharmacological intervention, and (iii) those based on spontaneous variations in a random population. Spontaneously hypertensive (SHR) and Naples High Excitability (NHE) rats show behavioral traits featuring the main aspects of ADHD in humans but show different changes in dopamine (DA) systems. In fact, the enzyme tyrosine hydroxylase is hyperexpressed in NHE rats and hypoexpressed in SHR. The DA transporter is hyperexpressed in both lines, although in the SHR, DAT activity is low (reduced DA uptake). The DA levels in the striatum and prefrontal cortex are increased in the juvenile SHR, but are decreased in handled young and non-handled older animals. The mRNA of the D1 DA receptor is upregulated in the prefrontal cortex of SHR and downregulated in NHE. The D2 DA receptors are likely to be hypofunctioning in SHR, although the experimental evidence is not univocal, whereas their mRNA is hyperexpressed in NHE. Thus, in SHR both the mesocortical and mesolimbic DA pathways appear to be involved, whereas in NHE only the mesocortical system. To understand the effects of methylphenidate, the elective ADHD drug treatment in humans, in a dysfunctioning DA system, we realized a simple mathematical model of DA regulation based on experimental data from electrophysiological, cyclic voltammetry, and microdialysis studies. This model allows the estimation of a higher firing frequency of DA neurons in SHR rats and suggests that methylphenidate increases attentive processes by regulating the firing rate of DA neurons. PMID:15303308

Cytochrome P450 isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica

PubMed Central

ZHANG, Jinhui; LI, Li; TANG, Suni; HALE, Thomas W.; XING, Chengguo; JIANG, Cheng; LÜ, Junxuan

2016-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 enzymes (CYP) whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal preparation, general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol and ketoconazole, substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0–48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0–48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D. PMID:26394652

Cytochrome P450 Isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica.

PubMed

Zhang, Jinhui; Li, Li; Tang, Suni; Hale, Thomas W; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 (CYP) enzymes, whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal (HLM) preparation, the general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol (NBN) and ketoconazole substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic (PK) study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0-48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0-48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barrett, Christopher A.; Martinez, Alonzo; McNamara, Bruce K.

International Atom Energy Agency (IAEA) safeguard verification measures in gaseous centrifuge enrichment plants (GCEPs) rely on environmental sampling, non-destructive assay (NDA), and destructive assay (DA) sampling and analysis to determine uranium enrichment. UF6 bias defect measurements are made by DA sampling and analysis to assure that enrichment is consistent with declarations. DA samples are collected from a limited number of cylinders for high precision, offsite mass spectrometer analysis. Samples are typically drawn from a sampling tap into a UF6 sample bottle, then packaged, sealed, and shipped under IAEA chain of custody to an offsite analytical laboratory. Future DA safeguard measuresmore » may require improvements in efficiency and effectiveness as GCEP capacities increase and UF6 shipping regulations become increasingly more restrictive. The Pacific Northwest National Laboratory (PNNL) DA sampler concept and Laser Ablation Absorption Ratio Spectrometry (LAARS) assay method are under development to potentially provide DA safeguard tools that increase inspection effectiveness and reduce sample shipping constraints. The PNNL DA sampler concept uses a handheld sampler to collect DA samples for either onsite LAARS assay or offsite laboratory analysis. The DA sampler design will use a small sampling planchet that is coated with an adsorptive film to collect controlled quantities of UF6 gas directly from a cylinder or process sampling tap. Development efforts are currently underway at PNNL to enhance LAARS assay performance to allow high-precision onsite bias defect measurements. In this paper, we report on the experimental investigation to develop adsorptive films for the PNNL DA sampler concept. These films are intended to efficiently capture UF6 and then stabilize the collected DA sample prior to onsite LAARS or offsite laboratory analysis. Several porous material composite films were investigated, including a film designed to maximize the chemical adsorption and binding of gaseous UF6 onto the sampling planchet.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nunes, O. A. C., E-mail: oacn@unb.br

We study the interaction of Dirac Fermions in monolayer graphene on a GaAs substrate in an applied electric field by the combined action of the extrinsic potential of piezoelectric surface acoustical phonons of GaAs (piezoelectric acoustical (PA)) and of the intrinsic deformation potential of acoustical phonons in graphene (deformation acoustical (DA)). We find that provided the dc field exceeds a threshold value, emission of piezoelectric (PA) and deformation (DA) acoustical phonons can be obtained in a wide frequency range up to terahertz at low and high temperatures. We found that the phonon amplification rate R{sup PA,DA} scales with T{sub BG}{supmore » S−1} (S=PA,DA), T{sub BG}{sup S} being the Block−Gru{sup ¨}neisen temperature. In the high-T Block−Gru{sup ¨}neisen regime, extrinsic PA phonon scattering is suppressed by intrinsic DA phonon scattering, where the ratio R{sup PA}/R{sup DA} scales with ≈1/√(n), n being the carrier concentration. We found that only for carrier concentration n≤10{sup 10}cm{sup −2}, R{sup PA}/R{sup DA}>1. In the low-T Block−Gru{sup ¨}neisen regime, and for n=10{sup 10}cm{sup −2}, the ratio R{sup PA}/R{sup DA} scales with T{sub BG}{sup DA}/T{sub BG}{sup PA}≈7.5 and R{sup PA}/R{sup DA}>1. In this regime, PA phonon dominates the electron scattering and R{sup PA}/R{sup DA}<1 otherwise. This study is relevant to the exploration of the acoustic properties of graphene and to the application of graphene as an acoustical phonon amplifier and a frequency-tunable acoustical phonon device.« less

The causes of parent-offspring transmission of drug abuse: a Swedish population-based study.

PubMed

Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

2015-01-01

While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n = 2,111,074), 'not-lived-with' (n = 165,315, where biological parents never lived with their offspring) and 'step' (n = 124,800 offspring)], which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in 'not-lived-with' and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than 'not-lived-with' child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats

PubMed Central

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-01-01

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats.

PubMed

Arnt, J; Hyttel, J

1985-01-01

The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

PubMed

Volkow, N D; Wang, G; Fowler, J S; Logan, J; Gerasimov, M; Maynard, L; Ding, Y; Gatley, S J; Gifford, A; Franceschi, D

2001-01-15

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that it elicits" and thus improving performance.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Gβγ subunit activation promotes dopamine efflux through the dopamine transporter

PubMed Central

Garcia-Olivares, J; Baust, T; Harris, S; Hamilton, P; Galli, A; Amara, SG; Torres, GE

2018-01-01

The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants—like cocaine and amphetamine—and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders. Previous studies have revealed a plethora of protein–protein interactions influencing DAT cellular localization and activity, suggesting that the fine-tuning of DA homeostasis involves multiple mechanisms. We recently reported that G-protein beta-gamma (Gβγ) subunits bind directly to DAT and decrease DA clearance. Here we show that Gβγ induces the release of DA through DAT. Specifically, a Gβγ-binding/activating peptide, mSIRK, increases DA efflux through DAT in heterologous cells and primary dopaminergic neurons in culture. Addition of the Gβγ inhibitor gallein or DAT inhibitors prevents this effect. Residues 582 to 596 in the DAT carboxy terminus were identified as the primary binding site of Gβγ. A TAT peptide containing the Gβγ-interacting domain of DAT blocked the ability of mSIRK to induce DA efflux, consistent with a direct interaction of Gβγ with the transporter. Finally, activation of a G-protein-coupled receptor, the muscarinic M5R, results in DAT-mediated DA efflux through a Gβγ-dependent mechanism. Collectively, our data show that Gβγ interacts with DAT to promote DA efflux. This novel mechanism may have important implications in the regulation of brain DA homeostasis. PMID:28894302

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

PubMed

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-04-30

DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

Biochemical and mass spectrometric characterization of the human CB2 cannabinoid receptor expressed in Pichia pastoris--importance of correct processing of the N-terminus.

PubMed

Zhang, Rundong; Kim, Tae-Kang; Qiao, Zhaun-Hong; Cai, Jian; Pierce, William M; Song, Zhao-Hui

2007-10-01

This study was conducted to optimize the expression of human CB2 cannabinoid receptors in methylotrophic yeast Pichia pastoris (P. pastoris). Two major species of expressed CB2 proteins were seen on Western blot, i.e., a 42 kDa band which matches the calculated molecular weight for tagged CB2, and a 52/55 kDa doublet. Treatment of membranes with N-glycosidase F or inclusion of tunicamycin in the culture medium during induction resulted in the disappearance of the 55 kDa, but not the 52 kDa band, suggesting that the 3 kDa extra in the 55 kDa band is due to N-glycosylation, but the 10 kDa extra in the 52 kDa band is not due to N-glycosylation. Anti-FLAG M1 antibody had a much higher preference for the 42 kDa band over the 52/55 kDa doublet, and a 10 kDa fragment recognized by anti-FLAG M2 antibody was generated by CNBr digestion of the 52/55 doublet. These data strongly support the hypothesis that the 10 kDa increase in molecular weight was due to unprocessed alpha-factor sequence. This conclusion was further validated by finding several peptide sequences for alpha-factor fragments at the N-terminal of the CB2 receptor using pepsin/chymotrypsin digestion and LC/MS/MS approaches. Importantly, unprocessed alpha-factor was found to be associated with poor ligand binding. In addition, controlling the level of CB2 protein expression was found to be critical for minimizing the presence of unprocessed alpha-factor sequence. The information gained from this study should aid the proper expression of not only CB2 receptor but also other members of the GPCR family in P. pastoris.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases.

PubMed

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca(2+) or Cl(-). Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase-glucoamylase and sucrase-isomaltase complexes.

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

PubMed

Özkan, Mazhar; Johnson, Nicholas W; Sehirli, Umit S; Woodhall, Gavin L; Stanford, Ian M

2017-01-01

The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases

PubMed Central

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca2+ or Cl−. Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase–glucoamylase and sucrase–isomaltase complexes. PMID:25161866

cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

PubMed

Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

2016-09-01

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. Copyright © 2016 Elsevier B.V. All rights reserved.

Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1991-03-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism.

The Atypical MAP Kinase SWIP-13/ERK8 Regulates Dopamine Transporters through a Rho-Dependent Mechanism

PubMed Central

Bermingham, Daniel P.; Snider, Sam L.; Miller, David M.

2017-01-01

The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/ hyperactivity disorder, schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking, and function, particularly in vivo, remain poorly understood, though recent studies have implicated rho-linked pathways in psychostimulant action. To identify genes that dictate the ability of DAT to sustain normal levels of DA clearance, we pursued a forward genetic screen in Caenorhabditis elegans based on the phenotype swimming-induced paralysis (Swip), a paralytic behavior observed in hermaphrodite worms with loss-of-function dat-1 mutations. Here, we report the identity of swip-13, which encodes a highly conserved ortholog of the human atypical MAP kinase ERK8. We present evidence that SWIP-13 acts presynaptically to insure adequate levels of surface DAT expression and DA clearance. Moreover, we provide in vitro and in vivo evidence supporting a conserved pathway involving SWIP-13/ERK8 activation of Rho GTPases that dictates DAT surface expression and function. SIGNIFICANCE STATEMENT Signaling by the neurotransmitter dopamine (DA) is tightly regulated by the DA transporter (DAT), insuring efficient DA clearance after release. Molecular networks that regulate DAT are poorly understood, particularly in vivo. Using a forward genetic screen in the nematode Caenorhabditis elegans, we implicate the atypical mitogen activated protein kinase, SWIP-13, in DAT regulation. Moreover, we provide in vitro and in vivo evidence that SWIP-13, as well as its human counterpart ERK8, regulate DAT surface availability via the activation of Rho proteins. Our findings implicate a novel pathway that regulates DA synaptic availability and that may contribute to risk for disorders linked to perturbed DA signaling. Targeting this pathway may be of value in the development of therapeutics in such disorders. PMID:28842414

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

PubMed

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Analysis of suffering at work in Family Health Support Centers.

PubMed

Nascimento, Débora Dupas Gonçalves do; Oliveira, Maria Amélia de Campos

2016-01-01

Analyzing the work process in the Family Health Support Center. An exploratory, descriptive case study using a qualitative approach. Focus groups were conducted with 20 workers of a Family Health Support Center, and the empirical material was subjected to content analysis technique and analyzed in light of Work Psychodynamics. The category of suffering is presented herein as arising from the dialectical contradiction between actual work and prescribed work, from resistance to the Family Health Support Center's proposal and a lack of understanding of their role; due to an immediatist and curative culture of the users and the Family Health Strategy; of the profile, overload and identification with work. The dialectical contradiction between expectations from Family Health Strategy teams and the work in the Family Health Support Center compromises its execution and creates suffering for workers. Analisar o processo de trabalho no Núcleo de Apoio à Saúde da Família. Estudo de caso exploratório, descritivo e de abordagem qualitativa. Grupos focais foram realizados com 20 trabalhadores do Núcleo de Apoio à Saúde da Família, o material empírico foi submetido à técnica de análise de conteúdo e analisado à luz da Psicodinâmica do Trabalho. Apresenta-se aqui a categoria sofrimento que neste estudo decorre da contradição dialética entre o trabalho real e o trabalho prescrito, da resistência à proposta do Núcleo de Apoio à Saúde da Família e da falta de compreensão de seu papel; da cultura imediatista e curativa do usuário e da Estratégia Saúde da Família; do perfil, sobrecarga e identificação com o trabalho. A contradição dialética entre expectativas das equipes da Estratégia Saúde da Família e o trabalho no Núcleo de Apoio à Saúde da Família compromete sua efetivação e gera sofrimento aos trabalhadores.

Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1

PubMed Central

Ries, Christian; Pitsch, Thomas; Mentele, Reinhard; Zahler, Stefan; Egea, Virginia; Nagase, Hideaki; Jochum, Marianne

2007-01-01

MMP-9 (matrix metalloproteinase 9) plays a critical role in tumour progression. Although the biochemical properties of the secreted form of proMMP-9 are well characterized, little is known about the function and activity of cell surface-associated proMMP-9. We purified a novel 82 kDa species of proMMP-9 from the plasma membrane of THP-1 leukaemic cells, which has substantial differences from the secreted 94 kDa proMMP-9. The 82 kDa form was not detected in the medium even upon stimulation with a phorbol ester. It is truncated by nine amino acid residues at its N-terminus, lacks O-linked oligosaccharides present in the 94 kDa proMMP-9, but retains N-linked carbohydrates. Incubation of 94 kDa proMMP-9 with MMP-3 generated the well-known 82 kDa active form, but the 82 kDa proMMP-9 was converted into an active species of 35 kDa, which was also produced by autocatalytic processing in the absence of activating enzymes. The activated 35 kDa MMP-9 efficiently degraded gelatins, native collagen type IV and fibronectin. The enzyme was less sensitive to TIMP-1 (tissue inhibitor of metalloproteinase 1) inhibition with IC50 values of 82 nM compared with 1 nM for the 82 kDa active MMP-9. The synthetic MMP inhibitor GM6001 blocked the activity of both enzymes, with similar IC50 values below 1 nM. The 82 kDa proMMP-9 is also produced in HL-60 and NB4 leukaemic cell lines as well as ex vivo leukaemic blast cells. It is, however, absent from neutrophils and mononuclear cells isolated from peripheral blood of healthy individuals. Thus, the 82 kDa proMMP-9 expressed on the surface of malignant cells may escape inhibition by natural TIMP-1, thereby facilitating cellular invasion in vivo. PMID:17489740

Biosynthesis, processing, and subcellular localization of rat spermbeta-D-galactosidase.

PubMed

Chayko, C A; Orgebin-Crist, M C; Skudlarek, M D; Tulsiani, D R

2000-09-01

During spermatogenesis, spermatids synthesize constituent proteins present in mature spermatozoa; however, little information exists on the molecular processes involved. In previous studies, this laboratory reported the characterization of rat sperm beta-D-galactosidase. In this paper, we report the localization of this enzyme along with its biosynthesis and processing. An antibody against rat luminal fluid beta-D-galactosidase was used to immunolocalize the enzyme in the testis and in epididymal spermatozoa. We found that beta-D-galactosidase is localized within the acrosomal cap of spermatids and in the acrosome and cytoplasmic droplet of epididymal spermatozoa. A combination of germ cell radiolabeling, immunoprecipitation, SDS-PAGE, and autoradiography revealed that spermatids produce two forms of beta-D-galactosidase, 90 and 88 kDa. During pulse-chase analysis, a 56-kDa form appeared. Treatment of beta-D-galactosidase immunoprecipitates from testicular spermatozoa with N-glycanase or Endo H revealed that both the 90- and 88-kDa forms become a 70-kDa polypeptide on SDS-PAGE. Since Endo H or N-glycanase treatment provided similar results, the presence of extensive N-linked high mannose/hybrid-type glycans on these proteins is indicated. Treatment of the 56-kDa form of beta-D-galactosidase with Endo H or N-glycanase resulted in the appearance of 52- and 50-kDa forms, respectively. This result suggests that the 56-kDa form contains N-linked high mannose/hybrid as well as complex oligosaccharides. During epididymal maturation, the 90-kDa form of beta-D-galactosidase persists in caput epididymal spermatozoa and is gradually converted to a major 74-kDa form in cauda spermatozoa. In addition to the 90- to 74-kDa forms, cauda spermatozoa show a 56- to 52-kDa form on Western immunoblots. Since only the high-molecular weight forms of beta-D-galactosidase are present on immunoblots of isolated sperm heads, we suggest that they are acrosomal in origin and that the 56-kDa form, which is processed to 52 kDa in cauda spermatozoa, is associated with the cytoplasmic droplet.

Peer Deviance, Parental Divorce, and Genetic Risk in the Prediction of Drug Abuse in a Nationwide Swedish Sample

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-01-01

IMPORTANCE Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). OBJECTIVES To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS Studies of future DA registration in 1 401 698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. MAIN OUTCOMES AND MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND RELEVANCE With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors. PMID:24576925

Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-04-01

Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

PubMed

Zeller, Thomas; Langhoff, Ralf; Rocha-Singh, Krishna J; Jaff, Michael R; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-09-01

Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB ( P =0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P =0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB ( P =0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB ( P =0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB ( P =0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB ( P =0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB ( P =0.86). DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. Copyright © 2017 The Author(s).

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency

PubMed Central

Langhoff, Ralf; Rocha-Singh, Krishna J.; Jaff, Michael R.; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-01-01

Background— Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. Methods and Results— DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency—A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). Conclusions— DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. PMID:28916599

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers.

PubMed

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals' emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington's diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 10 7 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level.

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers

PubMed Central

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Background Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals’ emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington’s diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. Purpose The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Methods Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. Results A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 107 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. Conclusion A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level. PMID:29713165

Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell Mediated by Dopamine and Acetylcholine Receptors.

PubMed

Shin, Jung Hoon; Adrover, Martin F; Alvarez, Veronica A

2017-11-15

Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA-dependent behaviors such as reward-motivated learning and the response to drugs of abuse. A disynaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this disynaptic mechanism of DA transmission are not well understood in the NAc shell. In this study, in vitro fast-scan cyclic voltammetry was used to examine the modulation of DA transmission evoked by CINs firing in the shell of mice and compared with other striatal regions. We found that DA signals in the shell displayed significant degree of summation in response to train stimulation of CINs, contrary to core and dorsal striatum. The summation was amplified by a D2-like receptor antagonist and experiments with mice with targeted deletion of D2 receptors to DANs or CINs revealed that D2 receptors in CINs mediate a fast inhibition observed within 100 ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a slower inhibition that peaks at ∼500 ms. ACh also contributes to the use-dependent inhibition of DA release through muscarinic receptors only in the shell, where higher activity of acetylcholinesterase minimizes nAChR desensitization and promotes summation. These findings show that DA signals are modulated differentially by endogenous DA and ACh in the shell, which may underlie the unique features of shell DA signals in vivo SIGNIFICANCE STATEMENT The present study reports that dopamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summation in the shell and shows unique modulation by endogenous DA and acetylcholine. Desensitization of nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition in the nucleus accumbens core and dorsal striatum, is also minimal in the shell in part due to elevated acetylcholinesterase activity. This distinctive modulation of DA transmission in the shell may have functional implications in the acquisition of reward-motivated behaviors and reward seeking. Copyright © 2017 the authors 0270-6474/17/3711166-15$15.00/0.

Characterization of Optically and Electrically Evoked Dopamine Release in Striatal Slices from Digenic Knock-in Mice with DAT-Driven Expression of Channelrhodopsin

PubMed Central

2017-01-01

Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e.g., a receptor antagonist) indicate a regulatory role for the transmitter system interrogated. Optogenetic methods that allow specific stimulation of DA axons provide a complementary, bottom-up approach for elucidating factors that regulate DA release. To this end, we have characterized DA release evoked by local electrical and optical stimulation in striatal slices from mice that genetically express a variant of channelrhodopsin-2 (ChR2). Evoked increases in [DA]o in the dorsal and ventral striatum (dStr and vStr) were examined in a cross of a Cre-dependent ChR2 line (“Ai32” mice) with a DAT::Cre mouse line. In dStr, repeated optical pulse-train stimulation at the same recording site resulted in rundown of evoked [DA]o using heterozygous mice, which contrasted with the stability seen with electrical stimulation. Similar rundown was seen in the presence of a nicotinic acetylcholine receptor (nAChR) antagonist, implicating the absence of concurrent nAChR activation in DA release instability in slices. Rundown with optical stimulation in dStr could be circumvented by recording from a population of sites, each stimulated only once. Same-site rundown was less pronounced with single-pulse stimulation, and a stable baseline could be attained. In vStr, stable optically evoked increases in [DA]o at single sites could be achieved using heterozygous mice, although with relatively low peak [DA]o. Low release could be overcome by using mice with a second copy of the Ai32 allele, which doubled ChR2 expression. The characteristics reported here should help future practitioners decide which Ai32;DAT::Cre genotype and recording protocol is optimal for the striatal subregion to be examined. PMID:28177213

Differential effects of pyrethroid insecticides on extracellular dopamine in the striatum of freely moving rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mubarak Hossain, Muhammad; Suzuki, Tadahiko; United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193

2006-11-15

In order to obtain a more complete understanding of pyrethroid neurotoxicity, effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) on extracellular levels of dopamine (DA) and its metabolites in the striatum of conscious rats were studied by in vivo microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had a dual effect on DA release. The increase in the extracellular level of striatal DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60 mg/kg inhibited DA release to 63% and 52% of baseline with a peakmore » effect at 60-80 min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%, 56% and 45% of basal release, respectively, with a peak time of inhibition 40-80 min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the efflux for 40 min to 50% of basal release and then increased the efflux to a maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1 {mu}M tetrodotoxin, a Na{sup +} blocker through the dialysis probe completely prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was completely prevented by local infusion of 10 {mu}M nimodipine, an L-type Ca{sup ++} channel blocker. All three pyrethroids did not alter the extracellular levels of DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of deltamethrin. Our results demonstrate that striatal DA release and DA uptake are differentially affected by type I and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.« less

Phosphatidylcholine Coatings Deliver Local Antimicrobials and Reduce Infection in a Murine Model: A Preliminary Study.

PubMed

Harris, Michael A; Beenken, Karen E; Smeltzer, Mark S; Haggard, Warren O; Jennings, J Amber

2017-07-01

Phosphatidylcholine coatings have been shown to elute antibiotics for several days. A recently developed biofilm inhibitor, cis-2-decenoic acid (C2DA), has been shown to exhibit synergistic activity with several common antibiotics. This study aims to evaluate the effectiveness of C2DA and amikacin dual drug delivery from a phosphatidylcholine coating. (1) What are the in vitro elution profiles of amikacin and C2DA from phosphatidylcholine-coated coupons in incubated phosphate-buffered saline? (2) Does the presence of C2DA in eluate samples lower the amount of amikacin needed for bacterial inhibition in overnight bacterial turbidity assays? (3) Does addition of amikacin and C2DA result in decreased colony-forming units (CFUs) on wire implants and bone when compared with phosphatidylcholine coatings alone in a mouse model of periprosthetic joint infection? Effects of loading concentrations were assessed during 7-day in vitro elution studies for coatings containing all mixtures of 0%, 5%, 15%, and 25% wt of amikacin and C2DA (n = 4) through quantitative high-performance liquid chromatography concentration determination and plotting concentration eluted over time. Antimicrobial activity was assessed by overnight turbidity testing of elution study samples against Staphylococcus aureus or Pseudomonas aeruginosa. In vivo efficacy was assessed using phosphatidylcholine-coated wire implants in a murine (mouse) model of infection (n = 3). Wire implants were coated with phosphatidylcholine containing no antimicrobials, amikacin alone, C2DA alone, or amikacin and C2DA and then inserted into the intramedullary femur of each mouse and inoculated with S aureus. The number of viable bacterial colonies on the implant surface and in the surrounding bone was determined after 1 week with the goal of achieving complete bacterial clearance. Total viable CFU count and proportion of samples achieving complete clearance were compared between groups. Elution samples showed a burst response of amikacin and C2DA for 1 to 2 days with C2DA release continuing at low levels through Day 4. All tested eluate samples inhibited P aeruginosa. Samples from coatings containing 25% amikacin or 15% amikacin and any amount of C2DA were able to inhibit S aureus formation, but all coatings with 5% amikacin or 15% amikacin but no C2DA were not inhibitory. All in vivo treatment groups achieved complete bacterial clearance on the wire implant, and the C2DA alone and amikacin alone coatings cleared all CFUs in bone (pin: phosphatidylcholine only one of three; amikacin three of three, C2DA three of three, amikacin + C2DA three of three, p = 0.04 [Fisher's exact test]; bone: coating only: zero of three; amikacin: three of three; C2DA; three of three; C2DA + amikacin: one of three; p = 0.03 [Fisher's exact test]). Phosphatidylcholine coatings elute antimicrobials in vitro under infinite sink conditions for up to 4 days in phosphate-buffered saline and were able to reduce bacterial colonies in a preliminary in vivo model. Turbidity testing with eluate samples containing varying amounts of C2DA and amikacin agrees with previous studies showing synergy between them. Used as an adjunctive to systemic therapy, C2DA-loaded phosphatidylcholine coatings have potential value as a prophylactic infection prevention measure. Future studies may include different antibiotics, animal studies with larger sample sizes and more controls, and advanced coating delivery methods.

Does transition from the da Vinci Si to Xi robotic platform impact single-docking technique for robot-assisted laparoscopic nephroureterectomy?

PubMed

Patel, Manish N; Aboumohamed, Ahmed; Hemal, Ashok

2015-12-01

To describe our robot-assisted nephroureterectomy (RNU) technique for benign indications and RNU with en bloc excision of bladder cuff (BCE) and lymphadenectomy (LND) for malignant indications using the da Vinci Si and da Vinci Xi robotic platform, with its pros and cons. The port placement described for Si can be used for standard and S robotic systems. This is the first report in the literature on the use of the da Vinci Xi robotic platform for RNU. After a substantial experience of RNU using different da Vinci robots from the standard to the Si platform in a single-docking fashion for benign and malignant conditions, we started using the newly released da Vinci Xi robot since 2014. The most important differences are in port placement and effective use of the features of da Vinci Xi robot while performing simultaneous upper and lower tract surgery. Patient positioning, port placement, step-by-step technique of single docking RNU-LND-BCE using the da Vinci Si and da Vinci Xi robot are shown in an accompanying video with the goal that centres using either robotic system benefit from the hints and tips. The first segment of video describes RNU-LND-BCE using the da Vinci Si followed by the da Vinci Xi to highlight differences. There was no need for patient repositioning or robot re-docking with the new da Vinci Xi robotic platform. We have experience of using different robotic systems for single docking RNU in 70 cases for benign (15) and malignant (55) conditions. The da Vinci Xi robotic platform helps operating room personnel in its easy movement, allows easier patient side-docking with the help of its boom feature, in addition to easy and swift movements of the robotic arms. The patient clearance feature can be used to avoid collision with the robotic arms or the patient's body. In patients with challenging body habitus and in situations where bladder cuff management is difficult, modifications can be made through reassigning the camera to a different port with utilisation of the retargeting feature of the da Vinci Xi when working on the bladder cuff or in the pelvis. The vision of the camera used for da Vinci Xi was initially felt to be inferior to that of the da Vinci Si; however, with a subsequent software upgrade this was much improved. The base of the da Vinci Xi is bigger, which does not slide and occasionally requires a change in table placement/operating room setup, and requires side-docking especially when dealing with very tall and obese patients for pelvic surgery. RNU alone or with LND-BCE is a challenging surgical procedure that addresses the upper and lower urinary tract simultaneously. Single docking and single robotic port placement for RNU-LND-BCE has evolved with the development of different generations of the robotic system. These procedures can be performed safely and effectively using the da Vinci S, Si or Xi robotic platform. The new da Vinci Xi robotic platform is more user-friendly, has easy installation, and is intuitive for surgeons using its features. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2...

32 CFR 516.43 - Release of Army and other agency records.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Preservation of originals. To preserve the integrity of DA records, DA personnel will submit properly... otherwise by Litigation Division. (See 28 U.S.C. 1733.) (b) Authentication of copies. Copies of DA records approved for release can be authenticated for introduction in evidence by use of DA Form 4. (See § 516.25...

32 CFR 536.32 - Transfer of claims among armed services branches.

Code of Federal Regulations, 2010 CFR

2010-07-01

... take all actions on the claim. Where the DA is the lead agency, any final action will include other agencies. Similarly, where another agency is the lead agency, that agency will be requested to include DA... another agency has taken denial action on a claim that involves the DA, without informing the DA, and in...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

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Specificity and impact of adrenergic projections to the midbrain dopamine system

PubMed Central

Mejias-Aponte, Carlos A.

2016-01-01

Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. PMID:26820641

Gold Nanorod Mediated Mild Hyperthermia and PEGylated Human Serum Albumin Drug Delivery for Cancer Therapies

NASA Astrophysics Data System (ADS)

Mehtala, Jonathan G.

Photothermally active gold nanorods were used to sensitize cells to chemotherapeutic agents by producing mildly hyperthermic effects (42-43 °C). We examined the synergistic effects of GNR-mediated mild hyperthermia (MHT) on cisplatin (CP) activity against SKOV3 ovarian cancer cells. In vitro studies were performed using CP at cytostatic concentrations (5 μM) and mPEG-stabilized GNRs (lambdamax 815 nm) with near-infrared laser excitation for MHT (or external heating as a positive control), followed by 72 hours incubation at 37 °C. The amount of PEG-GNRs needed for GNR-mediated MHT was determined to be 1 μg/mL, several times lower than the loadings used in tumor tissue ablation. A cell viability assay indicated 80% enhancement in CP-mediated cytotoxicity 3 days after GNR-mediated MHT relative to the projected additive effect. A pilot in vivo study showed preliminary results that cisplatin chemotherapy can be developed in combination with low loadings of GNR-mediated MHT for localized MHT to treat tumors. Stable aqueous dispersions of citrate-stabilized gold nanorods were prepared in scalable fashion by surfactant exchange from cetyltrimethylammonium bromide (CTAB)-stabilized GNRs, using sodium polystyrenesulfonate (PSS) as a detergent. Nanoparticle tracking analysis (NTA) was used to measure the size of the Cit-GNR dispersions, which provides particle sizing resolution several times better than that of dynamic light scattering (DLS). Cit-GNRs were further functionalized with human serum albumin (HSA) and thiols and dithiocarbamates (DTCs) of varying molecular weights. The quality of the Cit-GNR dispersions allows us to address fundamental questions relating GNR stabilization to surface adsorption, including insights into the formation of the protein corona in serum-containing media. Mono-PEGylated human serum albumin was synthesized to investigate its ability to improve the bioavailability of the ability of paclitaxel (PTX), a poorly soluble drug. Matrix assisted laser desportion/ionization mass spectrometry was used to confirm the formation of the mono-PEGylated adduct, and HPLC analysis revealed that 70% of native HSA was converted to HSA-mPEG. A cell viability assay with MCF-7 breast cancer cells was used to measure the enhancement of the therapeutic efficacy of a PTX formulation with HSA, HSA-mPEG 5 kDa, or HSA-mPEG 20 kDa compared to PTX in PBS in the absence of HSA. We observed that the therapeutic efficacy of PTX was maximized when it was formulated in a 10:1 molar ratio with HSA, and for intermediate PTX doses (3.3 and 6.6 nM) the therapeutic efficacy of PTX with HSA-mPEG 20 kDa was greater than that for HSA-mPEG 5 kDa. These results suggest that PTX can bind to PEGylated HSA, and that most of the drug can be released.

Toxicity evaluation of glyphosate agrochemical components using Japanese medaka (Oryzias latipes) and DNA microarray gene expression analysis.

PubMed

Uchida, Masaya; Takumi, Shota; Tachikawa, Keiko; Yamauchi, Ryoko; Goto, Yoshiyuki; Matsusaki, Hiromi; Nakamura, Hiroshi; Kagami, Yoshihiro; Kusano, Teruhiko; Arizono, Koji

2012-01-01

Using glyphosate agrochemical components, we investigated their acute toxicity to juvenile Japanese medaka (Oryzias latipes) as well as their toxic impact at gene expression level on the liver tissues of adult medaka using DNA microarray. In our acute toxicity test, juvenile medaka were exposed for 96 hr to each of the following glyphosate agrochemical components: 10~160 mg/l of glyphosate, 1.25~20 mg/l of fatty acid alkanolamide surfactant (DA), and 12~416 mg/l of a fully formulated glyphosate herbicide. As a result, LC(50) values of glyphosate, DA, and the glyphosate herbicide were > 160 mg/l, 8.5 mg/l, and 76.8 mg/l, respectively. On the other hand, adult male medaka fish were exposed to each of the glyphosate agrochemical components for 48 hr at the following concentrations: 16 mg/l of glyphosate, 0.5 mg/l of DA, and 16 mg/l-glyphosate/0.5 mg/l-DA mixture. Interestingly, DNA microarray analysis revealed that there were no significant gene expression changes in the medaka liver after exposure to glyphosate. Nevertheless, 78 and 138 genes were significantly induced by DA and the glyphosate/DA mixture, respectively. Furthermore, we identified five common genes that were affected by DA and glyphosate/DA mixture. These results suggested that glyphosate itself possessed very low toxicity as previously reported by some researchers at least to the small laboratory fish, and the major toxicity of the glyphosate agrochemical resided mainly in DA and perhaps in unintentionally generated byproduct(s) of glyphosate-DA mixture.

The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation.

PubMed

Plesner, Bitten; Westh, Peter; Hvidt, Søren; Nielsen, Anders D

2011-06-01

The effects of GlycoPEGylation on the molar hydrodynamic volume of recombinant human rFVIIa were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10kDa PEG and a branched 40kDa PEG, respectively. Molar hydrodynamic volumes were determined by capillary viscometry and mass spectrometry. The intrinsic viscosities of rFVIIa, its two GlycoPEGylated compounds, and of linear 8kDa, 10kDa, 20kDa and branched 40kDa PEG polymers were determined. The measured intrinsic viscosity of rFVIIa is 6.0mL/g, while the intrinsic viscosities of 10kDa PEG-rFVIIa and 40kDa PEG-rFVIIa are 29.5mL/g and 79.0mL/g, respectively. The intrinsic viscosities of the linear PEG polymers are 20, 22.6 and 41.4mL/g for 8, 10, and 20kDa, respectively, and 61.1mL/g for the branched 40kDa PEG. From the results of the intrinsic viscosity and MALDI-TOF measurements it is evident, that the molar hydrodynamic volume of the conjugated protein is not just an addition of the molar hydrodynamic volume of the PEG and the protein. The molar hydrodynamic volume of the GlycoPEGylated protein is larger than the volume of its composites. These results suggest that both the linear and the branched PEG are not wrapped around the surface of rFVIIa but are chains that are significantly stretched out when attached to the protein. Copyright © 2011 Elsevier B.V. All rights reserved.

Electrochemical determination of dopamine and ascorbic acid at a novel gold nanoparticles distributed poly(4-aminothiophenol) modified electrode.

PubMed

Gopalan, Anantha Iyengar; Lee, Kwang-Pill; Manesh, Kalayil Manian; Santhosh, Padmanabhan; Kim, Jun Heon; Kang, Jae Soo

2007-03-15

A modified electrode is fabricated by embedding gold nanoparticles into a layer of electroactive polymer, poly(4-aminothiophenol) (PAT) on the surface of glassy carbon (GC) electrode. Cyclic voltammetry (CV) is performed to deposit PAT and concomitantly deposit Au nanoparticles. Field emission transmission electron microscopic image of the modified electrode, PAT-Au(nano)-ME, indicates the presence of uniformly distributed Au nanoparticles having the sizes of 8-10nm. Electrochemical behavior of the PAT-Au(nano)-ME towards detection of ascorbic acid (AA) and dopamine (DA) is studied using CV. Electrocatalytic determination of DA in the presence of fixed concentration of AA and vice versa, are studied using differential pulse voltammetry (DPV). PAT-Au(nano)-ME exhibits two well defined anodic peaks at the potential of 75 and 400mV for the oxidation of AA and DA, respectively with a potential difference of 325mV. Further, the simultaneous determination of AA and DA is studied by varying the concentration of AA and DA. PAT-Au(nano)-ME exhibits selectivity and sensitivity for the simultaneous determination of AA and DA without fouling by the oxidation products of AA or DA. PAT and Au nanoparticles provide synergic influence on the accurate electrochemical determination of AA or DA from a mixture having any one of the component (AA or DA) in excess. The practical analytical utilities of the PAT-Au(nano)-ME are demonstrated by the determination of DA and AA in dopamine hydrochloride injection and human blood serum samples.

Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex.

PubMed

Bassareo, Valentina; De Luca, Maria Antonietta; Di Chiara, Gaetano

2007-04-01

Conditioned stimuli (CSs) by pavlovian association with reinforcing drugs (US) are thought to play an important role in the acquisition, maintenance and relapse of drug dependence. The aim of this study was to investigate by microdialysis the impact of pavlovian drug CSs on behaviour and on basal and drug-stimulated dopamine (DA) in three terminal DA areas: nucleus accumbens shell, core and prefrontal cortex (PFCX). Conditioned rats were trained once a day for 3 days by presentation of Fonzies filled box (FFB, CS) for 10 min followed by administration of morphine (1 mg/kg), nicotine (0.4 mg/kg) or saline, respectively. Pseudo-conditioned rats were presented with the FFB 10 h after drug or saline administration. Rats were implanted with microdialysis probes in the shell, core and PFCX. The effect of stimuli conditioned with morphine and nicotine on DA and on DA response to drugs was studied. Drug CSs elicited incentive reactions and released DA in the shell and PFCX but not in the core. Pre-exposure to morphine CS potentiated DA release to morphine challenge in the shell but not in the core and PFCX. This effect was related to the challenge dose of morphine and was stimulus-specific since a food CS did not potentiate the shell DA response to morphine. Pre-exposure to nicotine CS potentiated DA release in the shell and PFCX. The results show that drug CSs stimulate DA release in the shell and medial PFCX and specifically potentiate the primary stimulant drug effects on DA transmission.

The occurrence of domoic acid linked to a toxic diatom bloom in a new potential vector: the tunicate Pyura chilensis (piure).

PubMed

López-Rivera, Américo; Pinto, Maricela; Insinilla, Andrea; Suárez Isla, Benjamín; Uribe, Eduardo; Alvarez, Gonzalo; Lehane, Mary; Furey, Ambrose; James, Kevin J

2009-11-01

The tunicate Pyura chilensis (Molina, 1782); Phylum Chordata; Subphylum Urochordata; Class Ascidiacea, common local name "piure" or sea squirt; a filter-feeder (plankton and suspended particles) sessile species; may play an important role in monitoring domoic acid (DA) the principal toxic component of Amnesic Shellfish Poisoning (ASP). Significant DA concentrations have been determined in tunicate samples, collected during a recent ASP outbreak in Bahía Inglesa, an important scallop (Argopecten purpuratus) farming area. Several infaunal species were tested for the presence of DA, in addition to the usual scallop monitoring programme. DA was found at sub-toxic levels in filtering bivalves such as mussels (Mytilus chilensis), large mussels (Aulacomya ater) and clams (Protothaca thaca) (6.4, 5.4 and 4.7 microg DA/g tissue respectively). Of particular interest was the observation of significant accumulations of toxic Pseudo-nitzschia sp. diatoms in the internal siphon and atrium spaces of the tunicate. Toxin distribution within major tunicate organs was heterogeneous with 8.7-15.5 microg DA/g in edible tissues, 14.9-17.9 microg DA/g in the fecal material and 13.6-32.7 microg DA/g in the gut content. DA was determined by HPLC-UV and confirmed by diode-array detection and LC-MS/MS analysis. This is the first report of the presence of DA in a tunicate that is regularly consumed by coastal populations. These results confirm the need to include these organisms in sanitation programs for marine toxins.

P2X1 Receptor-Mediated Ca2+ Influx Triggered by DA-9801 Potentiates Nerve Growth Factor-Induced Neurite Outgrowth.

PubMed

Back, Moon Jung; Lee, Hae Kyung; Lee, Joo Hyun; Fu, Zhicheng; Son, Mi Won; Choi, Sang Zin; Go, Hyo Sang; Yoo, Sungjae; Hwang, Sun Wook; Kim, Dae Kyong

2016-11-16

Nerve growth factor (NGF)-induced neuronal regeneration has emerged as a strategy to treat neuronal degeneration-associated disorders. However, direct NGF administration is limited by the occurrence of adverse effects at high doses of NGF. Therefore, development of a therapeutic strategy to promote the NGF trophic effect is required. In view of the lack of understanding of the mechanism for potentiating the NGF effect, this study investigated molecular targets of DA-9801, a well-standardized Dioscorea rhizome extract, which has a promoting effect on NGF. An increase in intracellular calcium ion level was induced by DA-9801, and chelation of extracellular calcium ions with ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) suppressed the potentiating effect of DA-9801 on NGF-induced neurite outgrowth. In addition, EGTA treatment reduced the DA-9801-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), the major mediators of neurite outgrowth. To find which calcium ion-permeable channel contributes to the calcium ion influx induced by DA-9801, we treated PC12 cells with various inhibitors of calcium ion-permeable channels. NF449, a P2X1 receptor selective antagonist, significantly abolished the potentiating effect of DA-9801 on NGF-induced neurite outgrowth and abrogated the DA-9801-induced ERK1/2 phosphorylation. In addition, transfection with siRNA of P2X1 receptor significantly reduced the DA-9801-enhanced neurite outgrowth. In conclusion, calcium ion influx through P2X1 receptor mediated the promoting effect of DA-9801 on NGF-induced neurite outgrowth via ERK1/2 phosphorylation.

PCA as a practical indicator of OPLS-DA model reliability.

PubMed

Worley, Bradley; Powers, Robert

Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) are powerful statistical modeling tools that provide insights into separations between experimental groups based on high-dimensional spectral measurements from NMR, MS or other analytical instrumentation. However, when used without validation, these tools may lead investigators to statistically unreliable conclusions. This danger is especially real for Partial Least Squares (PLS) and OPLS, which aggressively force separations between experimental groups. As a result, OPLS-DA is often used as an alternative method when PCA fails to expose group separation, but this practice is highly dangerous. Without rigorous validation, OPLS-DA can easily yield statistically unreliable group separation. A Monte Carlo analysis of PCA group separations and OPLS-DA cross-validation metrics was performed on NMR datasets with statistically significant separations in scores-space. A linearly increasing amount of Gaussian noise was added to each data matrix followed by the construction and validation of PCA and OPLS-DA models. With increasing added noise, the PCA scores-space distance between groups rapidly decreased and the OPLS-DA cross-validation statistics simultaneously deteriorated. A decrease in correlation between the estimated loadings (added noise) and the true (original) loadings was also observed. While the validity of the OPLS-DA model diminished with increasing added noise, the group separation in scores-space remained basically unaffected. Supported by the results of Monte Carlo analyses of PCA group separations and OPLS-DA cross-validation metrics, we provide practical guidelines and cross-validatory recommendations for reliable inference from PCA and OPLS-DA models.

Phosphorylation of the rat hepatic polymeric IgA receptor.

PubMed Central

Larkin, J M; Sztul, E S; Palade, G E

1986-01-01

In vivo labeling with [35S]cysteine has identified three transmembrane forms of the rat hepatic polymeric IgA receptor: (i) a 105-kDa core glycosylated precursor; (ii) a terminally glycosylated 116-kDa intermediate; and (iii) a mature 120-kDa form. In the current study we show that the 120-kDa form is phosphorylated. After in vivo labeling with [32P]orthophosphate, all receptor forms were immunoprecipitated from hepatic total microsomes (TM) (with an antireceptor antiserum), separated by NaDodSO4/PAGE, and detected by autoradiography. The 120-kDa form was selectively phosphorylated, whereas the 116- and 105-kDa forms incorporated no detectable 32P. To determine the topology of the phosphorylation sites, hepatic TM isolated from rats labeled in vivo with either [35S]cysteine or [32P]orthophosphate were treated with trypsin. TM were solubilized and receptors were immunoprecipitated from lysates. With increasing trypsin concentrations, the [35S]cysteine-labeled receptor triplet was degraded to a trypsin-resistant doublet of approximately 95 and 85 kDa, indicating that approximately 20 kDa was removed from the receptor endodomain by trypsin. The same treatment removed all detectable 32P from labeled receptors. Furthermore, no 32P was detected in the 80-kDa biliary form of the receptor. Serine was identified as the only phosphorylated residue in acid hydrolysates of 32P-labeled immunoprecipitated receptor. These findings indicate that (i) the 120-kDa form is the only phosphorylated species of the receptor; and (ii) the phosphorylated residues are serine(s) located in the endodomain of the protein. Images PMID:3460069

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

Enhanced dopamine release by dopamine transport inhibitors described by a restricted diffusion model and fast scan cyclic voltammetry

PubMed Central

Hoffman, Alexander F.; Spivak, Charles E.; Lupica, Carl R.

2016-01-01

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple, 5 parameter, two compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using non-linear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altered Ca2+/Mg2+ ratio or tetrodotoxin (TTX), reduced the release parameter with no effect on the uptake parameter. The DAT inhibitors methylenedioxypyrovalerone (MDPV), cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa-opioid receptor (KOR) agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data. PMID:27018734

Enhanced Dopamine Release by Dopamine Transport Inhibitors Described by a Restricted Diffusion Model and Fast-Scan Cyclic Voltammetry.

PubMed

Hoffman, Alexander F; Spivak, Charles E; Lupica, Carl R

2016-06-15

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple five-parameter, two-compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using nonlinear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altering the Ca(2+)/Mg(2+) ratio or adding tetrodotoxin reduced the release parameter with no effect on the uptake parameter. DAT inhibitors methylenedioxypyrovalerone, cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa opioid receptor agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons.

PubMed

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C; Bunney, Benjamin S; Peterson, Bradley S

2012-11-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Onsite Gaseous Centrifuge Enrichment Plant UF6 Cylinder Destructive Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong

2012-07-17

The IAEA safeguards approach for gaseous centrifuge enrichment plants (GCEPs) includes measurements of gross, partial, and bias defects in a statistical sampling plan. These safeguard methods consist principally of mass and enrichment nondestructive assay (NDA) verification. Destructive assay (DA) samples are collected from a limited number of cylinders for high precision offsite mass spectrometer analysis. DA is typically used to quantify bias defects in the GCEP material balance. Under current safeguards measures, the operator collects a DA sample from a sample tap following homogenization. The sample is collected in a small UF6 sample bottle, then sealed and shipped under IAEAmore » chain of custody to an offsite analytical laboratory. Current practice is expensive and resource intensive. We propose a new and novel approach for performing onsite gaseous UF6 DA analysis that provides rapid and accurate assessment of enrichment bias defects. DA samples are collected using a custom sampling device attached to a conventional sample tap. A few micrograms of gaseous UF6 is chemically adsorbed onto a sampling coupon in a matter of minutes. The collected DA sample is then analyzed onsite using Laser Ablation Absorption Ratio Spectrometry-Destructive Assay (LAARS-DA). DA results are determined in a matter of minutes at sufficient accuracy to support reliable bias defect conclusions, while greatly reducing DA sample volume, analysis time, and cost.« less

Dopamine modulates male sexual behavior in Japanese quail in part via actions on noradrenergic receptors.

PubMed

Cornil, Charlotte A; Dejace, Christel; Ball, Gregory F; Balthazart, Jacques

2005-08-30

In rats, dopamine (DA) facilitates male sexual behavior through its combined action on D1- and D2-like receptors, in the medial preoptic area (MPOA) as well as other brain areas. In Japanese quail, systemic injections of dopaminergic drugs suggested a similar pharmacology but central injections have never been performed. Recent electrophysiological experiments demonstrated that DA effects in the MPOA of quail are mediated mainly through the activation of alpha2-noradrenergic receptors. Previous studies of DA action on behavior used specific dopaminergic agonists/antagonists and therefore unintentionally avoided the potential cross-reaction with alpha2-receptors. The present study was thus designed to investigate directly the effects of DA on male sexual behavior and to test whether the interaction of DA with heterologous receptors affects this behavior. Intracerebroventricular (i.c.v.) injection of DA or NE inhibited copulation in a dose-dependent manner. Systemic injections of yohimbine, an alpha2-noradrenergic antagonist, modulated copulation in a bimodal manner depending on the dose injected. Interestingly, a behaviorally ineffective dose of yohimbine markedly reduced the inhibitory effects of DA when injected 15min before. Together, these results show for the first time that i.c.v. injections of DA itself inhibit male sexual behavior in quail and suggest that the interaction of DA with alpha2-receptors has behavioral significance.

Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model

PubMed Central

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-01-01

Background/Aims DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Methods Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. Results In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. Conclusions The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity. PMID:25071903

Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

PubMed

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-07-01

DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.

PubMed

Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min

2014-04-01

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

DA-Raf, a dominant-negative antagonist of the Ras-ERK pathway, is a putative tumor suppressor.

PubMed

Kanno, Emiri; Kawasaki, Osamu; Takahashi, Kazuya; Takano, Kazunori; Endo, Takeshi

2018-01-01

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Death Anxiety in Persons with HIV/AIDS: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Miller, Audrey K.; Lee, Brittany L.; Henderson, Craig E.

2012-01-01

One of the most commonly cited psychological sequelae of HIV/AIDS is anxiety regarding death due to the illness (i.e., death anxiety; DA). However, extant research is inconclusive on several empirical issues, such as DA's relation to HIV/AIDS diagnostic status, the impact of illness-related symptoms on DA, and factors that may protect against DA.…

The Case for Dynamic Assessment in Speech and Language Therapy

ERIC Educational Resources Information Center

Hasson, Natalie

2007-01-01

This paper highlights the appeal of dynamic assessment (DA) for speech and language therapists (SLTs), and describes the usefulness of various DA models and methods. It describes the background to DA, and the uses to which DA has been put, by educational psychologists in the UK, and by SLTs in the USA. The research and development of methods of DA…

32 CFR 635.18 - Identifying criminal incidents and subjects of investigation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reported as the subject of an offense on DA Form 3975 when credible information exists that the person or... actions will not be based solely on the listing of an individual or legal entity as a subject on DA Form... entity is entered in the subject block of the DA Form 3975, their identity is recorded in DA automated...

Explaining the disease phenotype of intergenic SNP through predicted long range regulation

PubMed Central

Chen, Jingqi; Tian, Weidong

2016-01-01

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID:27280978

"Click chemistry" in tailor-made polymethacrylates bearing reactive furfuryl functionality: a new class of self-healing polymeric material.

PubMed

Kavitha, A Amalin; Singha, Nikhil K

2009-07-01

This investigation reports the effective use of the Diels-Alder (DA) reaction, a "click reaction" in the preparation of thermally amendable and self-healing polymeric materials having reactive furfuryl functionality. In this case, the DA and retro-DA (rDA) reactions were carried out between the tailor-made homo- and copolymer of furfuryl methacrylate prepared by atom-transfer radical polymerization and a bismaleimide (BM). The kinetic studies of DA and rDA reactions were carried out using Fourier transform infrared spectroscopy. The DA polymers were insoluble in toluene at room temperature. When the DA polymers were heated at 100 degrees C in toluene, it was soluble. This is because of the cleavage between furfuryl functionality and BM. The chemical cross-link density was determined by the Flory-Rehner equation. The cross-linked polymer showed much greater adhesive strength at room temperature, but the adhesive strength was quite low at higher temperature. The self-healing capability was studied by using scanning electron microscopy analysis. The thermal and dynamic mechanical properties of the thermally amendable cross-linked materials were investigated by thermogravimetric analysis and dynamic mechanical analysis.

Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis.

PubMed

Karrer, Teresa M; Josef, Anika K; Mata, Rui; Morris, Evan D; Samanez-Larkin, Gregory R

2017-09-01

Many theories of cognitive aging are based on evidence that dopamine (DA) declines with age. Here, we performed a systematic meta-analysis of cross-sectional positron emission tomography and single-photon emission-computed tomography studies on the average effects of age on distinct DA targets (receptors, transporters, or relevant enzymes) in healthy adults (N = 95 studies including 2611 participants). Results revealed significant moderate to large, negative effects of age on DA transporters and receptors. Age had a significantly larger effect on D1- than D2-like receptors. In contrast, there was no significant effect of age on DA synthesis capacity. The average age reductions across the DA system were 3.7%-14.0% per decade. A meta-regression found only DA target as a significant moderator of the age effect. This study precisely quantifies prior claims of reduced DA functionality with age. It also identifies presynaptic mechanisms (spared synthesis capacity and reduced DA transporters) that may partially account for previously unexplained phenomena whereby older adults appear to use dopaminergic resources effectively. Recommendations for future studies including minimum required samples sizes are provided. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Absorption, distribution, metabolism, and excretion of decursin and decursinol angelate from Angelica gigas Nakai.

PubMed

Kim, Kang Min; Kim, Myo Jeong; Kang, Jae Seon

2009-12-01

The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.

Evaluation of cephamycins as supplements to selective agar for detecting Campylobacter spp. in chicken carcass rinses.

PubMed

Chon, Jung-Whan; Kim, Young-Ji; Kim, Hong-Seok; Kim, Dong-Hyeon; Kim, Hyunsook; Song, Kwang-Young; Sung, Kidon; Seo, Kun-Ho

2016-04-16

Although cefoperazone is the most commonly used antibiotic in Campylobacter-selective media, the distribution of cefoperazone-resistant bacteria such as extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is increasing. Here we evaluated the potential of cephamycins for use as supplements to improve modified charcoal-cefoperazone-deoxycholate agar (mCCDA) by replacing cefoperazone with the same concentrations (32 mg/L) of cefotetan (modified charcoal-cefotetan-deoxycholate agar, mCCtDA) and cefoxitin (modified charcoal-cefoxitin-deoxycholate agar, mCCxDA). In chicken carcass rinse samples, the number of mCCDA plates detecting for Campylobacter (18/70, 26%) was significantly lower than that of mCCtDA (42/70, 60%) or mCCxDA plates (40/70, 57%). The number of mCCDA plates (70/70, 100%) that were contaminated with non-Campylobacter species was significantly higher than that of mCCtDA (20/70, 29%) or mCCxDA plates (21/70, 30%). The most common competing species identified using mCCDA was ESBL-producing E. coli, while Pseudomonas species frequently appeared on mCCtDA and mCCxDA. Copyright © 2016. Published by Elsevier B.V.

Adolescent Stimulation of D2 Receptors Alters the Maturation of Dopamine-dependent Goal-Directed Behavior

PubMed Central

Naneix, Fabien; Marchand, Alain R; Pichon, Anaïs; Pape, Jean- Rémi; Coutureau, Etienne

2013-01-01

Adolescence is a period of high sensitivity to drugs and rewards, characterized by the immaturity of decision-making abilities. A chronic stimulation of reward systems during this period might constitute a factor of vulnerability to the development of psychiatric disorders. However, the long-term consequences of such an exposure have seldom been explored. Here, we investigate at the adult age the effects of chronic dopamine (DA) stimulation during adolescence on both the maturation of DA systems and the cognitive processes underlying goal-directed actions. We first demonstrate that chronic stimulation of D2 receptors by quinpirole during adolescence alters the development of DA systems. This treatment has particularly prominent effects on the mesocortical DA pathway where it decreases DA fibers density, DA concentration, and DA receptors expression. Furthermore, we show that quinpirole-treated rats exhibit specific impairments in instrumental goal-directed behavior, as they fail to adapt their action when action–outcome relationships change in a contingency degradation procedure. These results therefore highlight the vulnerability of DA system and prefrontal areas to prolonged stimulation during adolescence, and its potential long-term impact on cognitive functions. PMID:23443719

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time Task in Rats.

PubMed

Boekhoudt, Linde; Voets, Elisa S; Flores-Dourojeanni, Jacques P; Luijendijk, Mieneke Cm; Vanderschuren, Louk Jmj; Adan, Roger Ah

2017-05-01

Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats. We found that activation of DA neurons in both the VTA and SNc impaired attention by increasing trial omissions. In addition, SNc DA neuron activation decreased attentional accuracy. Surprisingly, enhanced DA neuron activity did not affect impulsive action in this task. These results show that enhanced midbrain DA neuronal activity induces deficits in attentional performance, but not impulsivity. Furthermore, DA neurons in the VTA and SNc have different roles in regulating attention. These findings contribute to our understanding of the neural substrates underlying attention deficits and impulsivity, and provide valuable insights to improve treatment of these symptoms.

Effect of β,β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo.

PubMed

Fan, Yingying; Jin, Shaoju; He, Jun; Shao, Zhenjun; Yan, Jiao; Feng, Ting; Li, Hong

2012-01-01

In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed that DA could inhibit tumor cell growth in a time- and dose-dependent manner. Flow cytometry showed that DA blocks the cell cycle at G(0)/G(1) phase. Western blotting results demonstrated that the induction of apoptosis by DA correlated with the induction of pro-apoptotic proteins Bax, and Bid, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. Furthermore, treatment of HCT-116 bearing nude mice with DA significantly retarded the growth of xenografts. Consistent with the results in vitro, the DA-mediated suppression of HCT-116 xenografts correlated with Bax and Bcl-2. Taken together, these results suggest that DA could be a novel and promising approach to the treatment of CRC.

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

PubMed

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.