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Sample records for isoformes neuronales des

  1. neuronales artificiales

    Directory of Open Access Journals (Sweden)

    Bartolomé Drozdowicz

    2005-01-01

    Full Text Available La segmentación de Imágenes de Resonancia Magnética (IRM es su descomposición en unidades naturales, tejidos normales (sustancia gris, sustancia blanca, fluido cerebro espinal, etc. y posibles tejidos patológicos (tumores, edema, etc. Las IRM son una herramienta de diagnóstico estándar, y, a diferencia de los otros métodos de estudios por imagen (TAC, PET, etc., tienen características multidimensionales, ya que existen diferentes modalidades para generar las imágenes (T1, T2, DP, que son utilizadas para conformar los patrones empleados durante el entrenamiento y el testeo de las redes. La segmentación es particularmente importante en aplicaciones como: extracción de características anatómicas, medición volumétrica, visualización 3D, compresión de datos, planeamiento de radioterapia y planeamiento de cirugía. El objetivo de la investigación cuyos resultados se exponen fue explorar el potencial de diferentes estructuras de redes neuronales para realizar la segmentación de IRM del cerebro y analizar los diferentes procesos de preprocesamiento de datos, necesarios para obtener la mayor eficiencia de las redes.

  2. Neuronale Korrelate sozialer Interaktion beim Menschen und deren genetische Modulation unter besonderer Berücksichtigung des Spiegelneuronensystems

    OpenAIRE

    Cordes, Andrea

    2013-01-01

    Die in vielen Lebenssituationen über Erfolg und Misserfolg, Sympathie und Antipathie entscheidende, unterschiedlich ausgeprägte Fähigkeit zur sozialen Interaktion ist Gegenstand neurowissenschaftlicher Untersuchungen. Die Versuche einer kortikalen Lokalisierung führten zur Beschreibung des Spiegelneuronensystems (SNS) in Hirnregionen, die sowohl beim Ausführen einer Aktion Aktivität zeigten als auch beim Beobachten derselben beim Gegenüber. Die stärkste Aktivierung dieser Areale wurde bei sch...

  3. Modélisation du changement d’échelles en télédétection par une méthode neuronale : application a l’étude de l’évolution de l’occupation hivernale des sols en Bretagne

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    Thomas Houet

    2004-05-01

    Full Text Available Le suivi de la couverture hivernale des sols constitue un des principaux enjeux de la réduction de la pollution de la ressource en eau en Bretagne, la présence de la végétation entravant les transferts de flux polluants vers les cours d’eau. Le suivi du ratio « sols nus / sols couverts » peut être réalisé à l’aide d’instruments satellitaires de façon quotidienne à une échelle régionale, mais à une résolution spatiale grossière par des capteurs de type SPOT VEGETATION (1 km. Il peut également être effectué à une résolution spatiale fine par des capteurs tel que SPOT HRVIR (20 m mais avec une acquisition d’images une ou deux fois par hiver seulement sur un territoire plus limité. Toute évolution de ce ratio, détectée à l’échelle régionale, peut être issue de variations de la couverture hivernale des sols, mais également de l’influence de facteurs climatiques. Les changements observés doivent alors être validés par une analyse à l’échelle locale. Le lien entre les images des deux capteurs est établi à partir du développement d’une méthode neuronale basée sur une carte de Kohonen. L’originalité de cette méthode réside dans l’utilisation de la dimension temporelle pour résoudre ce problème de changement d’échelles.

  4. Data mining utilizando redes neuronales

    OpenAIRE

    Ale, Juan María; Bot, Romina Laura

    2004-01-01

    Las Redes Neuronales son ampliamente utilizadas para tareas relacionadas con reconocimiento de patrones y clasificación. Aunque son clasificadores muy precisos, no son comúnmente utilizadas para Data Mining porque producen modelos de aprendizaje inexplicables. El algoritmo TREPAN extrae hipótesis explicables de una Red Neuronal entrenada. Las hipótesis producidas por el algoritmo se representan con un árbol de decisión que aproxima a la red. Los árboles de decisión extraídos por TREPAN no pue...

  5. Controladores neuronales en robótica evolutiva

    OpenAIRE

    Fernández León, José A.; Acosta, Gerardo

    2004-01-01

    Este trabajo consiste en el estudio de las características más relevantes de la metodología denominada Robótica Evolutiva, en cuanto a la construcción de controladores neuronales evolutivos genéticamente determinados. Dichos controladores son aplicados a un robot tipo Khepera para llevar a cabo tareas (por ejemplo: planificación de trayectorias en navegación de robots) dentro de un entrono no conocido previamente. Los controladores propuestos están basados en controladores neuronales de tiemp...

  6. Hypnose, sommeil, placebo ? : Les réponses de la Théorie neuronale de la Cognition – Tome 2

    OpenAIRE

    Touzet , Claude

    2014-01-01

    International audience; Initialement uniquement dédié aux quelques « faits » comme :l'hypnose, le plaisir, le sommeil et les rêves, la responsabilité, l'effet placebo et la schizophréniequi n'avaient pas reçu d'explications de la part de la Théorie neuronale de la Cognition (tome 1 – Conscience, intelligence, libre-arbitre), ce second opus a rapidement dévié de sa mission originale pour intégrer des aspects encore plus controversés, comme :- le paranormal,- l'influence de l'intention sur la r...

  7. CODIFICACIÓN DE ESTADOS FUNCIONALES EN REDES NEURONALES BIOLÓGICAS

    OpenAIRE

    Luis Carrillo-Reid; José Barga

    2008-01-01

    Un tema central para las neurociencias consiste en descifrar la forma en la cual las redes neuronales biológicas procesan la información y guardan memorias. En 1949 Donald Hebb propuso que la actividad reverberante de pequeños circuitos neuronales llamados "ensambles" funcionaría como el sustrato sobre el cual se construyen las rutas de la memoria. Sin embargo, para poder almacenar cualquier tipo de información compleja, los ensambles neuronales deberían tener la habilidad de organizarse en j...

  8. Aplicación de las Redes Neuronales en Medicina

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    Alberto Delgado

    1999-10-01

    Full Text Available Las redes neuronales artificiales son modelos matemáticos que pueden ser entrenados para aprender relaciones no lineales entre un conjunto de datos de entrada y un conjunto de datos de salida. En medicina la aplicación más común de estos modelos, es la clasificación de patrones con el propósito de apoyar al médico en el diagnóstico y tratamiento del paciente.

  9. Técnicas de reconocimiento facial mediante redes neuronales

    OpenAIRE

    Cabello Pardos, Enrique

    2011-01-01

    En esta Tesis se exploran soluciones a la verificación facial. Se han estudiado técnicas basadas en imágenes bidimensionales y se ha realizado un estudio inicial basado en un modelo tridimensional de la cara. Se han comparado tres clasificadores (k vecinos más cercanos, redes neuronales del tipo ñmciones de base radial y máquinas de vector soporte), mostrando los resultados obtenidos con los diferentes datos de entrada. En dos dimensiones se han propuesto dos técnicas de reducción de...

  10. Reconocimiento de imágenes utilizando redes neuronales artificiales

    OpenAIRE

    García García, Pedro Pablo

    2013-01-01

    Este trabajo describe el proceso de extracción de patrones característicos de imágenes,mediante la ayuda de Redes Neuronales Artificiales. La información de la Red Neuronal junto con datos adicionales de las imágenes, serán almacenados en una base de datos y consumidos por un servicio web. Un teléfono móvil con sistema operativo Android consumirá la información almacenada en el servicio web. Posteriormente al realizar una captura de imagen con la cámara del teléfono, este procesará la imag...

  11. Aplicaciones sobre plataformas de redes neuronales en tiempo real

    OpenAIRE

    Tosini, Marcelo Alejandro; Acosta, Nelson

    2003-01-01

    El presente trabajo pretende el diseño de una metodología para la construcción de aplicaciones basadas en redes neuronales sobre una plataforma Muren. Las aplicaciones se restringen a sistemas de control y reconocimiento de patrones por imágenes. Se describe la arquitectura del sistema de desarrollo Muren, basado en 2 procesadores ZISC de 78 neuronas cada uno, una FPGA Spartan II, bancos de memoria y lógica adicional de comunicación.

  12. Aplicaciones de redes neuronales en economía.

    Directory of Open Access Journals (Sweden)

    Pacheco Bonrostro, J.

    1997-01-01

    Full Text Available La metodología de las Redes Neuronales Artificiales, está siendo usada con profusión, dentro del campo de la Economía, hasta tal punto que existe una publicación bimensual, que trata específicamente estas aplicaciones a los mercados financieros: Neurove$t Journal. En este trabajo, se presentan las principales líneas de investigación existentes, a continuación la que nosotros estamos siguiendo, con algunos resultados iniciales, para finalizar con las líneas a seguir y una selección bibliográfica.

  13. Reconocimiento automático del habla con redes neuronales artificiales

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    Diego H. Milone

    2005-01-01

    Full Text Available En la última década se han investigado intensamente los fundamentos y aplicaciones de las redes neuronales artificiales y se ha invertido un gran esfuerzo en el área del reconocimiento automático del habla. Este trabajo presenta una extensa revisión y un análisis crítico de la aplicación de redes neuronales artificiales al reconocimiento automático del habla. Se mencionan los antecedentes de la década de los 80 y se describen los trabajos que constituyen una aplicación directa de técnicas clásicas de redes neuronales artificiales. Se discuten aquellos en los que se han desarrollado nuevas arquitecturas neuronales, orientadas a resolver el problema del reconocimiento automático del habla, y se presentan también numerosos trabajos que consisten en la combinación de redes neuronales artificiales y modelos ocultos de Markov. Finalmente se realiza un análisis comparativo de los diferentes enfoques y los puntos clave que guían las investigaciones en torno a nuevos paradigmas sobre este problema. ´

  14. Un nuevo enfoque para la resolución de problemas: redes neuronales

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    Jonatán Gómez Perdomo

    2015-05-01

    Full Text Available RESUMEN El siguiente artículo  expone los lineamientos generales de un nuevo enfoque para la resolución de problemas mediante computador. Inspiradas en las redes neuronales biológicas, las redes neuronales artifíciales han  mostrado mayor efectividad para resolver problemas que los enfoques tradicionales no han  solucionado o lo han hecho de manera parcial. En la actualidad este enfoque ha ganado un gran auge, lo cual ha generado en el país grupos de investigación que están trabajando sobre sí mismo. Como parte de su trabajo  en el grupo de la Universidad Nacional, los autores desarrollan una herramienta para el diseño, entrenamiento y simulación de redes neuronales artificiales. Las características generales de esta herramienta  se exponen al final.

  15. SISTEMA PARA EL ENTRENAMIENTO PARALELO DE REDES NEURONALES DE PROPAGACIÓN HACIA ATRÁS

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    Alejandro Rosete Suárez

    2006-04-01

    Full Text Available

    El objetivo principal de este trabajo es la exploración del uso de la programación paralela en la instrumentación de redes neuronales, específicamente este artículo trata del uso de tal procesamiento para acelerar la fase de entrenamiento de una red de propagación hacia atrás (BPN. Se describe la implementación y los resultados obtenidos con la red neuronal antes mencionada. El sistema está realizado de manera tal, que el usuario pueda ejecutarlo eficientemente con un amplio rango de aplicaciones neuronales. Para probar el algoritmo paralelo implementado se utilizó una aplicación neuronal real y los resultados obtenidos muestran lo beneficioso de usar el entrenamiento paralelo.

  16. Empleo de redes neuronales artificiales en redes de distribución eléctrica

    OpenAIRE

    Alexander Cabrera; Delmar Jaime; Dante Miraglia; Sergio de la Fé Dotres

    2011-01-01

    En el trabajo se muestran las experiencias alcanzadas  en la aplicación de las Redes Neuronales Artificiales para resolver problemas tales como  la predicción de carga y de pérdidas de energía en las líneas y la localización de zonas en falla en circuitos de distribución de la ciudad de Santiago de Cuba.

  17. CODIFICACIÓN DE ESTADOS FUNCIONALES EN REDES NEURONALES BIOLÓGICAS

    Directory of Open Access Journals (Sweden)

    Luis Carrillo-Reid

    2008-01-01

    Full Text Available Un tema central para las neurociencias consiste en descifrar la forma en la cual las redes neuronales biológicas procesan la información y guardan memorias. En 1949 Donald Hebb propuso que la actividad reverberante de pequeños circuitos neuronales llamados "ensambles" funcionaría como el sustrato sobre el cual se construyen las rutas de la memoria. Sin embargo, para poder almacenar cualquier tipo de información compleja, los ensambles neuronales deberían tener la habilidad de organizarse en jerarquías, es decir, pequeñas subrutinas que componen procedimientos más elaborados. Nuestros experimentos muestran que los circuitos con estas capacidades pueden encontrarse en pequeños pedazos de cerebro aislado in vitro y estudiarse con detalle. De esta manera, el cerebro como cualquier sistema puede ser entendido y estudiado de acuerdo con sus elementos básicos y sus reglas de composición; permitiéndonos entender desde la forma en la cual nos comunicamos hasta los hábitos que determinan nuestra vida cotidiana. Los hallazgos experimentales aquí descritos podrían sentar las bases para entender tanto los estados cerebrales normales como los patológicos, con lo cual será posible proponer soluciones para distintas enfermedades neurodegenerativas que tienen un gran impacto en la sociedad.

  18. Subpoblaciones neuronales presentes en el ganglio de la raíz dorsal

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    Marlén Martínez

    2000-09-01

    Full Text Available La función principal de las neuronas del ganglio de la raiz dorsal (GRD es transmitir la información sensorial desde la periferia hasta el sistema nervioso central. Dos clases de células están presentes en el ganglio: las células no neuronales y las neuronales. La heterogeneidad morfológica, fisiológica y bioquimica de la población neuronal permite diferenciarla en subpoblaciones. Morfológicarnente, se distinguen tres tipos neuronales (A, B y C segun el tamaño y las caracteristicas ultraestructurales. Fisiológicamente, hay una relación directa entre el tamaño, el diámetro de las fibras nerviosas y la velocidad con que conducen el impulso nervioso. Finalmente, el uso de marcadores (neuropéptidos, enzimas, receptores, etc. permite realizar una clasificación bioquímica, que es la más utilizada para estudiar la función neuronal. Este articulo revisa la evidencia experimental sobre el tema de la heterogeneidad neuronal del GRD v wresenta una correlación desde el punto de vista bioauimico v fisioló-o ico en los casos en dondé'hay información disponible. El esiudio de subpoblaciones en este ganglio resulta de bastante interés para investigaciones en neurociencias, principalmente en infecciones por virus neurotrópicos, traurnatismos del nervio periférico y el estudio de factores neurotróficos, entre otros.

  19. Redes neuronales en espectrometría y dosimetría de neutrones

    OpenAIRE

    Torre López, Jesús Alberto de la

    2017-01-01

    Este Trabajo de Fin de Grado tiene como objetivo fundamental la realización de experimentos y simulaciones que ayuden a la comprensión acerca de una de las herramientas de predicción de valores más potentes de la inteligencia artificial como son las Redes Neuronales Artificiales. Su aplicación en este trabajo será muy concreta, en el campo de la espectrometría y dosimetría de neutrones, sin embargo, sus posibles aplicaciones abarcan un campo mucho más amplio, lo cual hace de ellas una herr...

  20. Predicción de la demanda eléctrica horaria mediante redes neuronales artificiales.

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    Mallo González, Carlos

    2004-01-01

    Full Text Available En este trabajo se realiza una introducción a los modelos neuronales y se explora su aplicabilidad en el terreno de la economía cuantitativa como instrumento de modelización y predicción no paramétrica. A tal objeto hemos desarrollado un modelo de Red Neuronal Artificial que posteriormente aplicaríamos en la predicción de la demanda horaria de energía eléctrica con datos reales. Los resultados así obtenidos con los ofrecidos por las metodologías convencionales de ajuste y predicción

  1. Discriminación entre strain y temperatura en un sistema BOTDA mediante redes neuronales artificiales

    OpenAIRE

    Ruiz Lombera, Rubén; Piccolo, Arianna; Fuentes Cayón, Alberto; López Higuera, José Miguel; Mirapeix Serrano, Jesús María

    2017-01-01

    RESUMEN: En este artículo se propone el uso de un enfoque basado en inteligencia artificial, en particular en redes neuronales artificiales, para conseguir una discriminación automática en medidas de strain y temperatura en sistemas sensores distribuidos basados en la dispersión estimulada de Brillouin en fibra óptica, en particular en implementaciones BOTDA. ABSTRACT: We present in this paper the employment of artificial intelligence, in particular artificial neural networks, as a possibl...

  2. Herramientas modernas en redes neuronales: la librería Keras

    OpenAIRE

    Antona Cortés, Carlos

    2017-01-01

    El mundo de las redes neuronales está en auge. Poder simular el cerebro humano en un ordenador, parece ser uno de los hitos más prometedores de la informática. Es cierto que este hito todavía no se ha conseguido, pero mediante algoritmos de machine learning, ya es posible entrenar máquinas para que aprendan de forma parecida a como lo hará nuestro cerebro. El objetivo de este Trabajo de Fin de Grado es poner en práctica estos algoritmos utilizando la librería Keras. En primer lugar, se har...

  3. Using neuronal nets for modelling and control of internal combustion engines; Der Einsatz neuronaler Netze zur Modellierung, Steuerung und Regelung von Verbrennungsmotoren

    Energy Technology Data Exchange (ETDEWEB)

    Isermann, R.; Hafner, M.; Mueller, N.; Schueler, M. [Technische Univ. Darmstadt (Germany). Inst. fuer Regelungstechnik

    1999-07-01

    Design and testing of digital electronic control systems necessitate relatively accurate mathematical models of the static and dynamic characteristics of internal combustion engines. Control variables are injection volume, injection angle, ignition point and several others, which means a large number of characteristic fields and long measuring times in engine test stands. Neuronal nets enable a more compact description than characteristic field grids and are also more easily adaptable in test stand measurements. The contribution describes a particularly favourable local linear radial basis function net (LOLIMOT) and shows how it can be used for modelling the steady-state and dynamic exhaust characteristics of a diesel engine and the dynamic characteristics of an exhaust turbocharger. It also shows how combustion chamber control with adaptive control of the ignition pooint can be designed for a spark ignition engine with the aid of a neuronal net. [German] Entwurf und Test von digitalelektronischen Steuerungen und Regelungen erfordern in zunehmendem Masse relativ genaue mathematische Modelle fuer das statische und dynamische Gesamtverhalten von Verbrennungsmotoren. Ausser den Stellgroessen Einspritzmenge, Einspritzwinkel und Zuendzeitpunkt kommen noch weitere Stellgroessen hinzu. Die Zahl der in modernen Motorsteuerungen zu realisierenden Kennfelder steigt deshalb sehr stark an und damit auch die erforderliche Messzeit an Motorenpruefstaenden. Kuenstliche neuronale Netze bieten nun die Moeglichkeit, mehrdimensionale Kennfelder wesentlich kompakter zu beschreiben als Rasterkennfelder. Sie erlauben ausserdem eine wesentlich bessere Adaption bei Pruefstandsversuchen. Im Beitrag wird ein besonders geeignetes lokal lineares Radial-Basis-Funktions-Netz (LOLIMOT) beschrieben und dessen Anwendung gezeigt zur Modellierung des stationaeren und dynamischen Abgasverhaltens eines Dieselmotors und des dynamischen Verhaltens eines Abgas-Turboladers. Dann wird gezeigt, wie man eine

  4. Uso de redes neuronales para optimizar simulaciones en un modelo de flujo de pasajeros en aeropuertos

    Directory of Open Access Journals (Sweden)

    Joaquin Pacheco

    2002-01-01

    Full Text Available Uno de nuestros principales objetivos es el diseño de métodos de aprendizaje de redes neuronales que sean rápidos a la vez que den buenas soluciones o vectores de pesos. Una de las aplicaciones donde se necesita un método rápido (on-line de aprendizaje de las redes neuronales es en la optimización de simulaciones. En este informe se proponen un sencillo algoritmo de búsqueda local para optimizar simulaciones, con una aplicación a un interesante modelo de flujo de pasajeros en un aeropuerto. En este problema se contemplan la minimización del tiempo de recorrido de los pasajeros con una adecuada distribución de los recursos. Este método incorpora el uso de una red neuronal para acelerar la optimización. Se va a comparar el efecto del uso de los pesos obtenidos por diferentes métodos de aprendizaje de la red neuronal, propuestos recientemente para este fin.

  5. LAS REDES NEURONALES Y LA EVALUACIÓN DEL RIESGO DE CRÉDITO

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    Fredy Ocaris Pérez Ramírez

    2007-01-01

    Full Text Available A pesar del escepticismo del mundo académico sobre los avances de la inteligencia artificial, las redes neuronales han abierto un campo de exploración bursátil que aún tiene mucho por investigar. Atendiendo a las ventajas del uso de las redes neuronales artificiales (ANN, por sus siglas en inglés y a su capacidad para estimar modelos no lineales, en este artículo se muestra la aplicación de las redes neuronales a la cuantificación del riesgo de crédito. Además, se hace el desarrollo teórico de los fundamentos básicos de las redes neuronales. Para presentar las metodologías de medición de riesgo de crédito basados en redes neuronales, y aplicarlas a la base de datos de una cartera comercial, fue necesario elaborar un análisis exploratorio de cada una de las variables e investigar la correlación entre ellas. El objetivo del análisis es encontrar algunas relaciones para grupos determinados de la población, de acuerdo con sus características particulares. Por tanto, se cruzan variables de cada cliente, del crédito y del comportamiento contra la variable default (fallidos y no fallidos. Variable que establece un procedimiento de clasificación, y permite determinar las ponderaciones necesarias y, además, establece la probabilidad de fallido.In spite of the skepticism of the academic world on the advances of artificial intelligence, the neuronal networks have opened up a field of stock-exchange exploration that has still so much to research. Upon expounding the advantages of the usage of artificial neuronal network (ANN and its capacity to estimate nonlinear models this article shows the application of the neuronal networks on the quantification of the credit risk. Furthermore, the article carries out a theoretical development of the basic foundations of neuronal networks. In order to present the methodologies of measurements of credit risk, based upon the neuronal networks and to apply the to the data base of a commercial

  6. Aproximación de los problemas de optimización por redes neuronales artificiales

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    Caballero Fernandez, Rafael

    2001-01-01

    Full Text Available En el presente artículo, pretendemos aportar un conocimiento de cómo puede aproximarse un problema de optimización mediante la dinámica de las redes neuronales artificiales, específicamente mediante las redes de tipo Hopfield. La elección de este tipo de redes radica en el objetivo que nos hemos propuesto en el presente trabajo, la resolución on-line de los problemas de optimización lineal, cuadrática, no lineal y combinatoria. Construimos, desarrollamos y justificamos formalmente una metodología integral que permite recoger los distintos tipos de problemas de optimización y construir una red neuronal de tipo Hopfield que los resuelva de una manera computacionalmente adecuada y formalmente correcta, comparando los resultados obtenidos con los publicados más recientemente.

  7. Clasificación de semillas de malezas utilizando redes neuronales artificiales

    OpenAIRE

    Gavarini, Sebastián; Trípode, Martín; Tosini, Marcelo Alejandro; Ceccatto, Hermenegildo Alejandro

    2004-01-01

    El presente trabajo es continuación del estudio llevado a cabo en [Cec2000], trabajo en el que se desarrolló una herramienta para procesar imágenes de semillas de malezas capturadas por una cámara de video, a las que se les extraían características morfológicas, de color y de textura. Parte del trabajo fue precisamente la selección de las características más relevantes. Posteriormente se analizaron métodos de clasificación por Naïve Bayes [Alf2002] y Redes Neuronales Artificiales FeedForwa...

  8. SIMULACIÓN MEDIANTE REDES NEURONALES DEL ENFRIAMIENTO DEL ARCO ELÉCTRICO EN DISYUNTORES DE ALTA TENSIÓN

    Directory of Open Access Journals (Sweden)

    ALEXANDRO BRYANTSEVICH

    2010-07-01

    Full Text Available La formulación de los modelos analíticos de enfriamiento de los arcos eléctricos en disyuntores de alta tensión todavía presenta muchas dificultades, y requiere nuevas hipótesis que los simplifique sustancialmente en relación con la realidad. Desde un punto de vista técnico, la aplicación de las redes neuronales podría ser una fuente objetiva para la simulación del enfriamiento del arco eléctrico, y para obtener resultados más cercanos a las propiedades reales del interruptor. En este trabajo se describe la problemática del desarrollo de modelos analíticos vinculados al enfriamiento del arco eléctrico de disyuntores de alta tensión mediante redes neuronales.

  9. Neural correlates of working memory deficits in schizophrenic patients. Ways to establish neurocognitive endophenotypes of psychiatric disorders; Neuronale Korrelate gestoerter Arbeitsgedaechtnisfunktionen bei schizophrenen Patienten. Ansaetze zur Etablierung neurokognitiver Endophaenotypen psychiatrischer Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, O. [Universitaet des Saarlandes, Klinik fuer Psychiatrie und Psychotherapie, Homburg (Saar) (Germany); Max-Planck-Institut fuer Kognitions- und Neurowissenschaften, Leipzig (Germany); Gruber, E.; Falkai, P. [Universitaet des Saarlandes, Klinik fuer Psychiatrie und Psychotherapie, Homburg (Saar) (Germany)

    2005-02-01

    This article briefly reviews some methodological limitations of functional neuroimaging studies in psychiatric patients. We argue that the investigation of the neural substrates of cognitive deficits in psychiatric disorders requires a combination of functional neuroimaging studies in healthy subjects with corresponding behavioral experiments in patients. In order to exemplify this methodological approach we review recent findings regarding the functional neuroanatomy of distinct components of human working memory and provide evidence for selective dysfunctions of cortical networks that underlie specific working memory deficits in schizophrenia. This identification of subgroups of schizophrenic patients according to neurocognitive parameters may facilitate the establishment of behavioral and neurophysiological endophenotypes and the development of a neurobiological classification of psychiatric disorders. (orig.) [German] Dieser Beitrag befasst sich mit einigen methodischen Problemen funktionell-bildgebender Studien mit psychiatrischen Patienten, aufgrund derer die Untersuchung der neuronalen Korrelate kognitiver Defizite bei psychiatrischen Erkrankungen einer Kombination funktionell-bildgebender Studien bei gesunden Normalprobanden mit Verhaltensuntersuchungen bei Patienten bedarf. Dieser methodische Ansatz wird am Beispiel von Arbeitsgedaechtnisfunktionen erlaeutert, wobei zunaechst neuere Erkenntnisse zur funktionellen Neuroanatomie verschiedener Komponenten des menschlichen Arbeitsgedaechtnisses referiert werden. Anschliessend werden bei schizophrenen Patienten erhobene Befunde vorgestellt, die auf spezifische Stoerungen der funktionellen Integritaet neuronaler Netzwerke mit Arbeitsgedaechtnisfunktionen hinweisen. Die damit verbundene Identifikation von Subgruppen schizophrener Patienten koennte zur Etablierung verhaltensneurophysiologisch definierter Endophaenotypen psychiatrischer Stoerungsbilder fuehren und die Entwicklung einer neurowissenschaftlich

  10. Realidad Virtual Acústica: El Abordaje de las Redes Neuronales Artificiales

    Directory of Open Access Journals (Sweden)

    Jose Francisco Lucio

    2015-05-01

    Full Text Available En este trabajo se presenta un nuevo abordaje para obtener las respuestas impulsivas biauriculares (BIRs para un sistema de aurilización utilizando un conjunto de redes neuronales artificiales (RNAs. El método propuesto es capaz de reconstruir las respuestas impulsivas asociadas a la cabeza humana (HRIRs por medio de modificación espectral y de interpolación espacial. Para poder cubrir todo el espacio auditivo de recepción, sin aumentar la complejidad de la arquitectura de la red, una estructura con varias RNAs (conjunto fue adoptada, donde cada red opera en una región específica del espacio (gomo. El error de modelaje en el dominio de la frecuencia es investigado considerando la naturaleza logarítmica de la audición humana. A través de la metodología propuesta se obtuvo un ahorro del tiempo de procesamiento computacional de aproximadamente 62% en relación al método tradicional de procesamiento de señales utilizado para aurilización. La aplicabilidad del nuevo método en sistemas de aurilización es reforzada mediante un análisis comparativo de los resultados, que incluyen la generación de las BIRs y el cálculo de un parámetro acústico biauricular (IACF, los cuales muestran errores con magnitudes reducidas.

  11. Estrategias para el entrenamiento de redes neuronales de números difusos

    Directory of Open Access Journals (Sweden)

    Edwin Villarreal López

    2014-04-01

    Full Text Available El propósito de este artículo es presentar estrategias generales de entrenamiento para redes neuronales de números difusos utilizadas en el aprendizaje de sistemas a partir de información lingüística. Se exponen brevemente las principales tendencias en el entrenamiento de este tipo de sistemas y con base en ellas se proponen nuevas estrategias. La primera de ellas se basa en la retro-propagación del error cuadrático medio en todos los a-cortes para pesos crisp. La segunda hace uso de un algoritmo genético con codificación real para redes con pesos crisp. La tercera consiste en la retro-propagación del error en el valor promedio y la ambigüedad en todos los a-cortes para pesos difusos. Por último, se presenta una basada en la retro-propagación de una medida difusa del error para redes con pesos difusos. Se realiza una etapa experimental en la que se implementan los algoritmos desarrollados junto con algunos de los más representativos reportados en el estado del arte, permitiendo identificar para qué conjuntos de datos particulares resulta útil cada una de las estrategias. Finalmente, se aplican dichas estrategias para la implementación de un sistema de evaluación de impacto ambiental en vertederos.

  12. Geothermics and neural networks: A first approach; Geotermia y redes neuronales: Una primera aproximacion

    Energy Technology Data Exchange (ETDEWEB)

    Flores Armenta, Magaly del Carmen [Gerencia de Proyectos Geotermoelectricos de la Comision Federal de Electricidad, Morelia (Mexico); Barragan Orbe, Carlos [Comision Federal de Electricidad, Mexico, D. F. (Mexico)

    1995-09-01

    Neural networks have been hailed as the greatest technological advance since the transistor. They are predicted to be a common household item by the year 2000. This new form of machine intelligence is able to solve problems, without using rules of math, they only need examples to learn from. The first geothermal problem, to solve with this powerful tool, is the prediction of liquid and steam production, as well as the well`s termination in Los Humeros, Puebla, Mexico. The first attempt shows the learning`s capacity of the developed model, and its precision on the predictions that were done. [Espanol] Las redes neuronales se consideran como uno de los mas grandes avances tecnologicos desde la invencion del transistor, de tal forma que se perfilan como una de las herramientas mas comunes del ano 2000. Esta nueva forma de inteligencia artificial es capaz de resolver problemas sin utilizar reglas matematicas, solamente requiere de ejemplos para aprender de ellos. El primer problema geotermico, atacado con esta poderosa herramienta, es la prediccion de las producciones de vapor y liquido, asi como la terminacion de pozos en el campo geotermico de Los Humeros, Puebla, Mexico. Los primeros intentos demuestran la capacidad de aprender del modelo desarrollado, y su certeza en las predicciones realizadas.

  13. Un método cuantitativo para analizar redes neuronales marcadas por histoquímica para acetilcolinesterasa

    Directory of Open Access Journals (Sweden)

    Luz H. Camargo

    2004-12-01

    Full Text Available El análisis cualitativo de las redes neuronales por histoquímica enzimática se usa comúnmente en los estudios morfológicos tradicionales. Una limitante de este tipo de estudios consiste en la dificultad de obtener resultados cuantitativos. Este artículo presenta dos técnicas originales de procesamiento de imágenes para realizar estudios cuantitativos y un análisis comparativo entre ellas. Los resultados preliminares presentados permiten verificar la utilidad de la metodología aplicada.

  14. IDENTIFICACION DEL CILINDRO NUDOSO EN IMÁGENES TC DE TROZAS PODADAS DE PINUS RADIATA UTILIZANDO REDES NEURONALES ARTIFICIALES

    OpenAIRE

    Rojas Espinoza,Gerson; Ortiz Irribarren,Oscar

    2010-01-01

    La factibilidad de identificar el cilindro nudoso en imágenes de tomografía computarizada de rayos X (TC) de trozas podadas de pino radiata (Pinus radiata D. Don), fue evaluada utilizando un método de clasificación supervisada basado en Redes Neuronales Artificiales (RNA). El proceso de clasificación consideró también la identificación de la zona libre de defectos y nudos. Treinta trozas podadas de pino radiata fueron escaneadas en un escáner médico multi-slice de rayos X, donde las imágenes ...

  15. Pronóstico del IPC de la Bolsa Mexicana de Valores Mediante el Uso de Reglas y Redes Neuronales

    OpenAIRE

    Cázares Carrillo, Juan G.

    2004-01-01

    La presente investigación es un esfuerzo para el desarrollo de un pronosticador con resultados aceptables para el mercado de valores destinándose su uso como una herramienta de apoyo a la toma de decisiones financieras. El pronóstico se realiza mediante la identificación de patrones utilizando como herramientas técnicas de Inteligencia Artificial, específicamente Redes Neuronales de Retropropagación y Algoritmos Genéticos. Las principales aportaciones de la presente investigación son: la dete...

  16. Clasificación del clutter marino utilizando redes neuronales artificiales

    Directory of Open Access Journals (Sweden)

    Argel Gonzalez Padilla

    2013-04-01

    Full Text Available La detección de radar bajo la acción del clutter marino es un problema actual. La efectividad de esta detección puede ser mejorada o aún optimizada si el comportamiento estadístico de los parámetros de las señales dispersadas por la superficie del mar (clutter marino es conocida. En el presente trabajo, la mayoría de los modelos estadísticos del clutter marino bajo diferentes condiciones es dada y se logra en un solo documento de manera sintética agrupar un gran volumen de información, difícil de encontrar, y en muchos casos, de interpretar. La mayor contribución investigativa de este trabajo es la presentación de los fundamentos de un sistema auto adaptativo  para la detección de blancos de radar, basado en el reconocimiento de diferentes distribuciones que modelan las mediciones de amplituddelclutter marino, obtenida en un intervalo de tiempo dado. Realizando una clasificación más fina al especificar el rango de valores que toman los parámetros de la distribución, para el intervalo de tiempo que se analiza. Este sistema fue simulado satisfactoriamente utilizando redes neuronales.Los resultados revelaron que se puede realizar de forma efectiva el reconocimiento de distribuciones de mediciones de amplitud del clutter marino y de los parámetros de la distribución.

  17. Inflammatory lesions of the brainstem and the cerebellopontine angle; Entzuendungen des Hirnstamms und des Kleinhirnbrueckenwinkels

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, J.; Jaeger, L. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen (Germany). Institut fuer Klinische Radiologie

    2006-03-15

    Inflammatory lesions of the brainstem and the cerebellopontine angle are often critical for the patient, because crucial neuronal and vascular structures are found in this region. The patient's prognosis mainly depends on rapid identification of the inflammation site and the radiological evaluation of the inflammation pathogenesis to develop therapeutic strategies. Therefore, cross-sectional imaging is complementary to laboratory and CSF analysis as well as biopsies. This article gives a survey of inflammatory lesions of the brainstem and the cerebellopontine angle. (orig.) [German] Entzuendliche Erkrankungen des Hirnstamms und Kleinhirnbrueckenwinkels stellen nicht selten eine kritische Situation fuer den Patienten dar, da in diesen Regionen wichtige neuronale Strukturen und Gefaesse verlaufen. Die Prognose und das weitere therapeutische Vorgehen haengen entscheidend von einer schnellen Diagnose der Entzuendungslokalisation sowie einer bildmorphologischen Einordnung der Entzuendungspathogenese ab. Folglich ergaenzt die Schnittbildgebung entscheidend die Liquoranalyse, die Biopsie und die Laboruntersuchungen. In diesem Artikel soll eine Uebersicht ueber die verschiedenen entzuendlichen Veraenderungen des Hirnstamms und Kleinhirnbrueckenwinkels gegeben werden. (orig.)

  18. Redes Neuronales y su aplicación predictiva en la Bolsa de Valores española

    Directory of Open Access Journals (Sweden)

    Ibarra Alfaraz, J.A.

    1999-01-01

    Full Text Available Este trabajo recoge una visión general de las redes neuronales y su tendencia en la investigación actual. Además de las aplicaciones conocidas donde las redes neuronales han demostrado su aplicabilidad se abren nuevos campos de investigación. En nuestro caso, nos centraremos en el área económica y más concretamente en la financiera. Esta metodología se aplica al caso concreto del análisis predictivo de la bolsa de valores, concretamente se utiliza el índice del mercado continuo de la bolsa española, Ibex-35, y los recientemente aparecidos índices sectoriales del Ibex: Servicios, Financiero, Utilities y Complementario. La red neuronal utilizada, Perceptron, ha sido entrenada con los datos reales procedentes de la bolsa de valores utilizando diferentes periodos de tiempo y efectuando cambios en los parámetros que condicionan la capacidad predictiva de la red. Los resultado se han contrastado con los obtenidos en otros trabajos empíricos realizados con metodologías clásicas.

  19. Estimación de la resistencia a la penetración de suelos usando redes neuronales artificiales

    Directory of Open Access Journals (Sweden)

    Nidia Johana Valdés Holguín

    2011-07-01

    Full Text Available Las redes neuronales artificiales, simuladoras del proceso de aprendizaje de las neuronas biológicas, han sido utilizadas con éxito en el cálculo de parámetros en diversos problemas de ingeniería en que las variables involucradas tienen una alta relación no lineal entre sí y la modelación no permite representar el problema mediante una función matemática de fácil deducción. En la ciencia del suelo la predicción de algunas propiedades involucra diversas variables que hacen de su estimación por medio de modelos matemáticos un proceso complejo, y trasladan la solución del problema al campo de la inteligencia artificial. En el presente artículo se reporta la elaboración de redes neuronales artificiales para la estimación de la resistencia a la penetración a diferentes profundidades de un suelo; se consideran como variables influyentes el contenido de humedad, la densidad, la carga estática y la presión de inflado. Los resultados muestran una mejor estimación para profundidades entre 20 cm y 30 cm.

  20. GENOMIQUE ET LIPIDES Génomique et métabolisme des lipides des plantes

    Directory of Open Access Journals (Sweden)

    Delseny Michel

    2002-03-01

    Full Text Available Il existe dans les bases de données publiques une énorme quantité de séquences d’ADN dérivées de plantes, et notamment la séquence complète du génome d’Arabidopsis thaliana, une plante modèle pour les oléagineux, proche parente du colza. Ces données constituent une ressource importante non seulement pour la compréhension de métabolisme lipidique et de sa régulation, mais aussi pour la sélection et le développement de variétés nouvelles d’oléagineux produisant davantage d’huiles ou des huiles de composition nouvelle. Cette abondance de séquences peut être exploitée, en utilisant les recherches d’homologies, pour identifier les gènes, pour obtenir des informations sur leur fonction, comme pour repérer des gènes candidats codant des fonctions nouvelles. L’analyse de ces bases de données a révélé que la majeure partie des gènes codant des enzymes impliquées dans le métabolisme lipidique appartient à des petites familles multigéniques, reflétant la diversification des fonctions des isoformes. Une analyse du catalogue des ADNc séquencés en aveugle reflète les niveaux d’expression des différents gènes et fournit un aperçu des régulations des flux au travers des voies métaboliques conduisant à la biosynthèse des lipides de réserve. La disponibilité de mutants et de lignées transgéniques d’Arabidopsis et le développement de puces à ADN qui permettent l’analyse simultanée de plusieurs milliers de gènes conduiront à une meilleure compréhension des facteurs qui régulent le métabolisme des huiles dans les graines. Une telle connaissance facilitera la manipulation de la composition des huiles et des quantités produites dans les graines.

  1. Uso de redes neuronales artificiales para mejorar el tránsito en las vías

    Directory of Open Access Journals (Sweden)

    Edwin Mejía

    2016-11-01

    Full Text Available Este artículo pretende dar una idea de cómo las Redes Neuronales Artificiales (ANNs, una técnica de la Inteligencia Artificial (IA, se puede acoplar a resolver el problema del tráfico en las vías de la ciudad de Riobamba, provincia de Chimborazo, país Ecuador, usando cuatro semáforos estándar, a través de un ejemplo se indica el uso de componentes electrónicos como FPGAs (Field Programmable Gate array y los sensores en este campo, a través de detectar y contar autos puede dar mayor fluidez al tráfico. La vía que mayor cantidad de autos tenga se dará mayor prioridad para la luz verde. Usando el algoritmo de aprendizaje de un Perceptrón Simple.

  2. Pronóstico de los índices accionarios DAX y S&P 500 con redes neuronales diferenciales

    Directory of Open Access Journals (Sweden)

    Francisco Ortiz Arango

    2013-01-01

    Full Text Available En este trabajo se utiliza una red neuronal diferencial (RND para describir las series de valores de cierre diarios de los índices accionarios DAX de Alemania y S&P 500 de Estados Unidos entre el periodo del 3 de julio de 2000 y el 13 de enero de 2012. Con la RND se lleva a cabo el pronóstico de los valores de cierre diarios de esos índices durante un periodo de cuatro semanas (del 16 de enero al 10 de febrero de 2012. Los resultados obtenidos confirman el hecho de que las redes neuronales diferenciales pueden constituirse en una de las herramientas más poderosas y precisas para poder pronosticar valores futuros de activos financieros.

  3. BIOINDICACIÓN DE LA CALIDAD DEL AGUA CON MACROINVERTEBRADOS ACUÁTICOS EN LA SABANA DE BOGOTÁ, UTILIZANDO REDES NEURONALES ARTIFICIALES

    Directory of Open Access Journals (Sweden)

    GUTIÉRREZ JUAN DAVID

    2004-06-01

    Full Text Available Se presenta una implementación de la metodología de redes neuronales (RN comoherramienta para la estimación de la calidad del agua en la cuenca alta y media del ríoBogotá, Colombia. Los datos usados provienen de 55 sitios correspondientes aonce cuencas de la sabana de Bogotá. Los resultados obtenidos con la aplicaciónde la RN fueron comparados con los valores del índice fisicoquímico Cfq y del índicede bioindicación ASPT (Average Score Per Taxon, para comprobar el grado deconfiabilidad de la metodología.Palabras clave. Redes neuronales,

  4. IMPLEMENTACIÓN DE REDES NEURONALES PARA LA DETECCIÓN DE LA PRESENCIA DE ENFERMEDADES EN EL CORAZÓN

    OpenAIRE

    José A. Avellaneda González; Cynthia M. Ochoa Rey

    2012-01-01

    A  continuación  por  medio  de  dos  métodos  para la implementación  de  redes  neuronales  y  una base  de  datos que presenta    diferentes    características    de pacientes, algunos presentan algún  tipo  de  enfermedad  del  corazón y otros  no.  Se desarrollo  en una  primera  parte redes neuronales  supervisadas, específicamente  se  implementa un perceptrón   multicapa;  la segunda parte plantea  redes  no supervisadas,  implementando una red ART2 (Adaptive resonance theory).: Época...

  5. Optimización de la Estimación de DOA en Sistemas de Antenas Inteligentes usando criterios de Redes Neuronales

    Directory of Open Access Journals (Sweden)

    Serguei Guerra Fernández

    2013-04-01

    Full Text Available La estimación DOA es uno de los principales problemas a resolver en las comunicaciones modernas. En el presente trabajo, se realiza un acercamiento a los sistemas de Antenas Inteligentes y los elementos teóricos referidos a la estimación de DOA, ecuaciones y modelos. Se estudian los métodos clásicos de estimación y las nuevas técnicas basadas en Redes Neuronales. Se traza una metodología para la obtención de resultados, a partir de parámetros medibles, en cada uno de los algoritmos de estimación sometidos a comparación. Finalmente, se analizan los resultados y se propone utilizar técnicas basadas en Redes Neuronales a fin de mejorar la estimación de DOA en Antenas Inteligentes.

  6. Diagnóstico automático del síndrome coronario agudo utilizando un sistema multiagente basado en redes neuronales

    Directory of Open Access Journals (Sweden)

    John Jaime Sprockel Díaz

    2017-05-01

    Conclusiones: Es posible desarrollar una herramienta para el diagnóstico automático del síndrome coronario agudo a partir de un sistema multiagente que ensamble la disposición tomada por un conjunto de redes neuronales artificiales, cuyo rendimiento permite su consideración para su implementación dentro de un sistema de soporte a las decisiones clínicas.

  7. Functional studies of sodium pump isoforms

    DEFF Research Database (Denmark)

    Clausen, Michael Jakob

    The Na+,K+-ATPase is an essential ion pump found in all animal cells. It uses the energy from ATP hydrolysis to export three Na+ and import two K+, both against their chemical gradients and for Na+ also against the electrical potential. Mammals require four Na+,K+-ATPase isoforms that each have...... unique expression profiles and specialized functional features. We use a Two Electrode Voltage Clamp setup to determine pre-steady-state and steady-state characteristics of each isoform and design chimeras to pin-point the structural elements responsible for observed differences. With this strategy we...

  8. Lipoprotein lipase isoelectric point isoforms in humans

    DEFF Research Database (Denmark)

    Badia-Villanueva, M.; Carulla, P.; Carrascal, M.

    2014-01-01

    -heparin plasma (PHP), LPL consists of a pattern of more than 8 forms of the same apparent molecular weight, but different isoelectric point (pI). In the present study we describe, for the first time, the existence of at least nine LPL pI isoforms in human PHP, with apparent pI between 6.8 and 8.6. Separation...

  9. Una técnica de pronóstico de señales basada en redes neuronales

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Ortiz T.

    2001-10-01

    Full Text Available El creciente interés por construir sistemas de procesamiento de señales mediante redes neuronales, especialmente durante los últimos veinte años, se debe a la posibilidad de avances significativos en campos poco explorados y cuyo manejo resulta de naturaleza compleja. Uno de estos campos es la predicción de señales. Una señal es una colección de valores que, generalmente, representan mediciones sucesivas de un evento del mundo real, los valores se toman durante un tiempo específico a intervalos regulares, representando una muestra del evento que se desea estudiar o de las características propias del mismo. La predicción de una señal consiste en obtener un conjunto de valores que, según un margen de error aceptable, constituyen una estimación del comportamiento futuro de la señal. El proceso de predicción es mucho más que la posición simplista de aventurar valores; puesto que requiere la construcción de un modelo adecuado de la dinámica del sistema a tratar.

  10. Identificación del estado de madurez de las frutas con redes neuronales artificiales, una revisión

    Directory of Open Access Journals (Sweden)

    Gustavo Andrés Figueredo-Ávila

    2016-01-01

    Full Text Available La aplicación de las Redes Neuronales Artificiales (RNA y de la visión artificial tiene cada vez más acogida en la industria de productos alimenticios; estas técnicas priorizan la clasificación, el reconocimiento de patrones y la predicción de las cosechas y de los cambios físicos de sus productos. En este artículo se define el concepto de red neuronal y se describen sus principales características y modelos, y, por otro lado, se define el concepto de procesamiento de imágenes digitales y las diferentes etapas que lo componen. Complementariamente, se exponen las generalidades de la inspección de frutas (enfocada en Colombia y sus técnicas. Finalmente, se especifican diferentes trabajos en los que se aplicaron técnicas de RNA y visión artificial en el campo de los productos alimenticios, dispuestos por áreas de  aplicación, y se identifica de manera concluyente el impacto que estas dos técnicas tienen para la clasificación, el reconocimiento de patrones y la predicción en el sector de productos alimenticios.

  11. EXPLORACIÓN CON REDES NEURONALES ARTIFICIALES PARA ESTIMAR LA RESISTENCIA A LA COMPRESIÓN, EN CONCRETOS FIBROREFORZADOS CON ACERO

    Directory of Open Access Journals (Sweden)

    Luis Octavio González Salcedo

    2012-01-01

    Full Text Available En diseño y construcción de estructuras de concreto, la resistencia a la compresión a 28 días de curado es la especificación de control de estabilidad de la obra. La inclusión de fibras como reforzamiento de la matriz cementicia permite una ganancia en sus propiedades, además de obtener un material de alto desempeño. En las normativas, se plantean formulaciones predictivas de la resistencia a la compresión basadas en unos pocos parámetros de composición del concreto, tales como la relación agua/cemento y el contenido de cemento Portland. Por otra parte, también se han planteado métodos de diseños de concreto para definir la ponderación de sus materiales componentes, teniendo como referencia la resistencia a la compresión del concreto simple. Además, las redes neuronales artificiales, como un símil de las neuronas biológicas, han sido utilizadas como herramientas de predicción de la resistencia a la compresión en el concreto, también con referencia al concreto simple, sin reforzamiento con fibras. Los antecedentes en este uso muestran que es interesante desarrollar aplicaciones en los concretos reforzados con fibras. En el presente trabajo se elaboraron redes neuronales artificiales para predecir la resistencia a la compresión en concretos reforzados con fibras de acero. Los resultados de los indicadores de desempeño mostraron que las redes neuronales artificiales elaboradas pueden realizar una aproximación adecuada al valor real de la propiedad mecánica.

  12. Uso de redes neuronales artificiales para identificación de personas mediante el reconocimiento de rostros de la Municipalidad de la Victoria - Lima - 2015

    OpenAIRE

    Arriola Ramírez, Franklin

    2015-01-01

    En el presente proyecto se aplicará reconocimiento de imágenes mediante redes neuronales para la identificación de rostros, lo cual será utilizado para el diseño de un prototipo que permita verificar que las personas que participen de las actividades organizadas por la Municipalidad de La Victoria-Lima sean solamente los beneficiarios debidamente registrados en los Programas Sociales. La identificación de rostros de personas será captada en tiempo real con una cámara ...

  13. Subpoblaciones neuronales presentes en cultivos primarios de ganglio espinal y su relación con la infección in vitro por virus de rabia

    OpenAIRE

    Hernán Hurtado; Jaime E. Castellanos; Niyibi Quiroga; Marlén Martínez

    2000-01-01

    El virus de la rabia presenta un fuerte tropismo neuronal y que produce una encefalitis generalmente letal. En un accidente rábico clásico, producido por la mordedura de un animal infectado, el virus es captado por terminaciones nerviosas motoras, autonómicas o sensoriales. Si es captado por estas últimas, el virus se transporta retrógradamente hacia los somas neuronales ubicados en los ganglios espinales y de...

  14. Estudio de los circuitos neuronales responsables de ritmopatías y déficit cognitivo en modelos experimentales de epilepsia del lóbulo temporal

    OpenAIRE

    Valero García, Manuel

    2017-01-01

    En periodos de inmovilidad y sueño de ondas lentas emerge en el hipocampo el patrón de actividad más síncrono del cerebro de mamífero: los eventos sharp wave (SPW-r). Gran número de trabajos han demostrado que el reclutamiento celular durante tales eventos recopila secuencias neuronales computacionalmente relevantes, fenómeno que subyace al proceso de consolidación de la memoria. Todas las condiciones que cursan con déficit cognitivos han sido asociadas a alteraciones en los SPW-r, incluyendo...

  15. Reconocimiento automático de locutor a través de aprendizaje automático mediante redes neuronales empleando el paquete de software libre Kaldi

    OpenAIRE

    Jiménez Andreu, Rubén

    2017-01-01

    El objetivo del presente Proyecto Fin de Máster es presentar algunas técnicas para reconocimiento de hablante empleando redes neuronales y deep learning. Como referencia se emplean vectors y un modelo universal basado en mezclas gaussianas (GMM-UBM) como método del estado del arte. El proceso de entrenamiento es realizado con la base de datos de audiolibros LibriSpeech. Esta base también se emplea para evaluar los modelos, junto con la de Speakers in the Wild, con locucion...

  16. “USO DE REDES NEURONALES ARTIFICIALES PARA OPTIMIZAR LA DOSIFICACIÓN DE COAGULANTES EN LA PLANTA DE TRATAMIENTO DE AGUA POTABLE - HUANCAYO”

    OpenAIRE

    Peña Rojas, Anieval Cirilo

    2016-01-01

    En la investigación se utilizaron las redes neuronales artificiales como herramienta para optimizar la cantidad de coagulante (Al2SO4) que se utiliza en el tratamiento del agua potable de la empresa SEDAM de la ciudad de Huancayo – Perú, donde la calidad del agua al ingreso a la planta de tratamiento tuvo variabilidad permanente de turbidez debido a las precipitaciones fluviales que se presentaron generalmente en los meses de octubre a marzo. Este fenómeno meteorológico alteró en corto tiempo...

  17. WT1 isoform expression pattern in acute myeloid leukemia.

    Science.gov (United States)

    Luna, Irene; Such, Esperanza; Cervera, Jose; Barragán, Eva; Ibañez, Mariam; Gómez-Seguí, Inés; López-Pavía, María; Llop, Marta; Fuster, Oscar; Dolz, Sandra; Oltra, Silvestre; Alonso, Carmen; Vera, Belén; Lorenzo, Ignacio; Martínez-Cuadrón, David; Montesinos, Pau; Senent, M Leonor; Moscardó, Federico; Bolufer, Pascual; Sanz, Miguel A

    2013-12-01

    WT1 plays a dual role in leukemia development, probably due to an imbalance in the expression of the 4 main WT1 isoforms. We quantify their expression and evaluate them in a series of AML patients. Our data showed a predominant expression of isoform D in AML, although in a lower quantity than in normal CD34+ cells. We found a positive correlation between the total WT1 expression and A, B and C isoforms. The overexpression of WT1 in AML might be due to a relative increase in A, B and C isoforms, together with a relative decrease in isoform D expression. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Detección en línea de onda-P en sismogramas 3-D utilizando redes neuronales

    Directory of Open Access Journals (Sweden)

    Alzate Carlos

    2003-08-01

    Full Text Available

    We have developed a P-wave arrival time detector of tectonic events over digital three-component records online. This process uses two different methods: the first one works with a LVR detector, and the second one uses a statistical classifier of classes (signal with P-wave and signal with seismic noise. Detection uses multi-layer perceptron neural network where is taken advantage of non-lineal input-output, relation, well-generalization, low computational demands, etc. These appropriate qualities for real time signal processing. The input data for the system becomes a normalized vector of seismic signal and its polarization arguments. Testes were done with data from IRIS and INGEOMINAS database. Although the system has a good perforance, its accuracy is not acceptable.

    Se desarrolla un detector en línea del tiempo de arribo de ondas P sobre registros electrónicos de tres componentes de eventos tectónicos. Se lleva a cabo la detección en línea de la onda-p empleando redes neuronales (RN, utilizando dos diferentes formas: en la primera se sintetiza el detector de LRV, mientras en la segunda se desarrolla un clasificador estadístico con las respectivas clases (señal con onda-p presente y señal con solo ruido presente. La detección se realiza empleando redes neuronales de tipo perceptrón multi-capa, en las cuales se aprovechan las siguientes cualidades: su capacidad de mapeo no lineal de entrada-salida, buena generalización, bajo costo computacional, entre otras. Las anteriores cualidades hacen que las RN sean apropiadas para el proceso de señales en tiempo real. Las entradas a la RN corresponden a

  19. PRONÓSTICO DE VENTAS: COMPARACIÓN DE PREDICCIÓN ENTRE REDES NEURONALES Y MÉTODO ESTADÍSTICO [doi: 10.5329/RECADM.20030201008

    Directory of Open Access Journals (Sweden)

    S. Nojek

    2003-05-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 RESUMEN Actualmente es común que las empresas realicen pronósticos de ventas para poder planificar más acertadamente su producción. El objetivo de este trabajo consiste en estudiar la predicción de ventas mediante el uso de redes neuronales, comparar los resultados obtenidos con los pronósticos de un método estadístico clásico y establecer los entornos más adecuados para su uso. Palabras Clave: Pronostico de Ventas – Predicción basada en Redes Neuronales.   ABSTRACT Companies usually need sales forecast for improving production planning. This research work pursues to study sales forecast based on neural networks and to compare this results with the ones based on classical statistical methods trying to specify the adequate business environment for using them Keywords: Sales Forecast – Forecasting based on Neural Networks

  20. Specific Profile of Tau Isoforms in Argyrophylic Grain Disease

    Directory of Open Access Journals (Sweden)

    Alberto Rábano

    2013-01-01

    Full Text Available Argyrophylic grain disease (AGD is a neurodegenerative condition that has been classified among the sporadic tauopathies. Entities in this group present intracellular aggregates of hyperphosphorylated tau, giving rise to characteristic neuronal and glial inclusions. In different tauopathies, the proportion of several tau isoforms present in the aggregates shows specific patterns. AGD has been tentatively classified in the 4R group (predominance of 4R tau isoforms together with progressive supranuclear palsy and corticobasal degeneration. Pick's disease is included in the 3R group (predominance of 3R isoforms, whereas tau pathology of Alzheimer's disease represents and intermediate group (3 or 4 repeats [3R plus 4R, respectively] isoforms. In this work, we have analyzed tau present in aggregates isolated from brain samples of patients with argyrophylic grain disease. Our results indicate that the main tau isoform present in aggregates obtained from patients with AGD is a hyperphosphorylated isoform containing exons 2 and 10 but lacking exon 3.

  1. Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Sergey V., E-mail: Sergey.Ivanov@med.nyu.edu [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States); Ivanova, Alla V.; Goparaju, Chandra M.V.; Chen, Yuanbin; Beck, Amanda; Pass, Harvey I. [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States)

    2009-05-08

    Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.

  2. Oxygenation properties and isoform diversity of snake hemoglobins

    DEFF Research Database (Denmark)

    Storz, Jay F.; Natarajan, Chandrasekhar; Moriyama, Hideaki

    2015-01-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer- dimer dissociation. However, standardized comparative data are lacking fo...... isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform....

  3. ANALYSE DES PERCEPTIONS LOCALES ET DES FACTEURS ...

    African Journals Online (AJOL)

    AISA

    1Faculté des Sciences Agronomiques (FSA), Université d'Abomey-Calavi (UAC), 01 BP 526 Cotonou Bénin. Email : cgbemavo@yahoo.fr. 2Institut National des Recherches Agricoles du Bénin, Centre de Recherches Agricoles d'Agonkanmey (CRA-A),. Laboratoire des Sciences du Sol, Eau et Environnement (LSSEE).

  4. Neuronal networks for the study of buildings thermal behavior; Redes neuronales para el estudio del comportamiento termico de edificios

    Energy Technology Data Exchange (ETDEWEB)

    Marincic, Irene [Universidad de Sonora (Mexico); Del Rio, J. Antonio [Centro Morelense de Innovacion y Transferencia Tecnologica (Mexico)

    2009-07-15

    The evaluation as well as the prediction of buildings thermal behavior involves complex calculations mainly because of its enormous number of variables, many of them difficult to determine. For this type of problems, a possibility is to resort to models of the black box type, that allow the characterization of the building with very few variables, for then to be able to predict its behavior under other circumstances, with greater certainty. One of the black box models of more and more used in diverse disciplines, is the one of the artificial neuronal networks (ANN). These can be used as an alternative method of analysis and prediction, particularly for cases in which many variables take part. In this work a preliminary study is presented that analyzes the accuracy of a model of neuronal network for the prediction of the inside temperatures of a building, given the outside temperatures. A very simple network, of 3 neurons, located in 2 layers is considered. The results of the inside temperatures obtained in the learning as well as in the prediction stage are analyzed, comparing them with the ones obtained using another model of black box previously developed by the authors, the one of the function responded in the dominion of frequencies. [Spanish] Tanto la evaluacion como la prediccion del comportamiento termico de los edificios involucra calculos complejos sobre todo por su enorme numero de variables, muchas de ellas dificiles de determinar. Para este tipo de problemas, una posibilidad es recurrir a modelos del tipo caja negra, que permiten caracterizar al edificio como muy pocas variables, para luego poder predecir su comportamiento bajo otras circunstancias, como mayor certeza. Uno de los modelos de caja negra cada vez mas utilizado en diversas disciplinas, es el de las redes neuronales artificiales (ANN). Estas pueden ser usadas como metodo alternativo de analisis y sobre todo de prediccion, particularmente para los casos en que intervienen muchas variables. En

  5. Artificial Neural Networks for Predicting Real Estate Prices || Redes neuronales artificiales para la predicción de precios inmobiliarios

    Directory of Open Access Journals (Sweden)

    Núñez Tabales, Julia M.

    2013-01-01

    Full Text Available Econometric models, in the estimation of real estate prices, are a useful and realistic approach for buyers and for local and fiscal authorities. From the classical hedonic models to more data driven procedures, based on Artificial Neural Networks (ANN, many papers have appeared in economic literature trying to compare the results attained with both approaches. We insist on the use of ANN, when there is enough statistical information, and will detail some comparisons to hedonic modeling, in a medium size city in the South of Spain, with an extensive set of data spanning over several years, collected before the actual downturn of the market. Exogenous variables include each dwelling's external and internal data (both numerical and qualitative, and data from the building in which it is located and its surroundings. Alternative models are estimated for several time intervals, and enabling the comparison of the effects of the rising prices during the bull market over the last decade. || Los modelos econométricos en la valoración de precios inmobiliarios constituyen una herramienta útil tanto para los compradores como para las autoridades locales y fiscales. Desde los modelos hedónicos clásicos hasta los planteamientos actuales a través de redes neuronales artificiales (RNA, han tenido lugar numerosas aportaciones en la literatura económica que tratan de comparar los resultados de ambos métodos. Insistimos en el empleo de RNA en el caso de disponer de suficiente información estadística. En este trabajo se aplica dicha metodología en una ciudad de tamaño medio situada en el sur de España, utilizando una extensa muestra de datos que comprende varios años precedentes a la crisis actual. Las variables utilizadas -tanto cuantitativas como cualitativas- incluyen datos externos e internos de la vivienda, del edificio en el que está localizada, así como de su entorno. Se construyen varios modelos alternativos para distintos intervalos de

  6. Modelisation des effets physico-techniques pour la conception des ...

    African Journals Online (AJOL)

    automatisation dans les installations industrielles a besoin d'une régulation automatique des commandes des processus technologiques pour lesquelles certaines contraintes sont à relever compte tenu des exigences des innovations scientifiques de ...

  7. Optimización de secciones de vigas y columnas para el cumplimiento de la deriva en edificaciones de concreto reforzado mediante Redes Neuronales Artificiales

    Directory of Open Access Journals (Sweden)

    Jorge Arcila Zea

    2014-01-01

    Full Text Available Este artículo presenta los resultados del uso de Redes Neuronales Artificiales (RNA para la estimación de secciones óptimas de vigas y columnas en concreto reforzado en edificaciones aporticadas simétricas de 1 a 6 pisos teniendo en cuenta los requisitos mínimos exigidos en la NSR-10 relacionados con la deriva y el diseño sísmico. Además se estudió la sensibilidad de la deriva respecto a los valores de dimensiones de vigas y de columnas, para que una vez se tenga una mejor comprensión de dicha relación, se puedan obtener diseños óptimos de manera más rápida, sencilla y confiable en comparación con los procedimientos utilizados actualmente.

  8. Teoría de precios de arbitraje. Evidencia empírica para Colombia a través de redes neuronales

    Directory of Open Access Journals (Sweden)

    Charle Londoño

    2011-07-01

    Full Text Available Esta investigación utiliza una red neuronal multicapa para relacionar el Índice General de Bolsa de Valores de Colombia (IGBC con fundamentales macroeconómicos y variables financieras. Proponemos dos modelos: un modelo APT (fundamentales macroeconómicos y un modelo APT modificado (fundamentales macroeconómicos + indicador de las bolsas del mundo; de acuerdo a nuestro análisis el APT tradicional se ajusta mejor para predecir el mercado de valores Colombiano. Los resultados confirman que las redes neuronales artificiales (ANN son más efectivas que los modelos estadísticos tradicionales por su capacidad explicativa y precisión.

  9. Modelación del crecimiento de pollitas Lohmann LSL con redes neuronales y modelos de regresión no lineal

    Directory of Open Access Journals (Sweden)

    Luis Galeano-Vasco

    2013-11-01

    Full Text Available Objetivo. Modelar la curva del crecimiento de aves de la línea Lohmann LSL utilizando modelos no lineales (MNL, no lineales mixtos (MNLM y redes neuronales artificiales (RNA. Materiales y métodos. Periódicamente se pesaron 33 aves en promedio, desde el día 21 al 196 de vida para un total de 558 registros individuales de peso. En el ajuste de la curva de crecimiento se utilizaron los modelos: no lineal de Von Bertalanffy (MNL, no lineal Mixto de Von Bertalanffy (MNLM y redes neuronales artificiales (RNA. Los modelos se compararon con coeficiente de correlación y medidas de presicion cuadrado medio del error (CME, desviación media absoluta (MAD y porcentaje de la media absoluta del error (MAPE. Resultados. Los valores de correlación entre los datos reales y estimados, fueron 0.999, 0.990 y 0.986 para MNLM, RNA y MNL respectivamente. El modelo más preciso con base en los criterios MAPE, MAD y CME fue el MNLM, seguido por la RNA. La grafica de predicción generada la RNA es similar a la del MNLM. La RNA presentó un desempeño superior al MLN. Conclusiones. El mejor modelo para la predicción de curvas de crecimiento de aves comerciales de la línea Lohmman LSL hasta los 196 días de edad, con múltiples mediciones por animal en el tiempo, fue el MNLM. La RNA presento un desempeño superior al MNL.

  10. Pronóstico del rendimiento del IPC (Índice de Precios y Cotizaciones mediante el uso de redes neuronales diferenciales

    Directory of Open Access Journals (Sweden)

    Agustín Ignacio Cabrera Llanos

    2012-01-01

    Full Text Available A través de los años, el uso de las redes neuronales artificiales como herramienta de simulación, modelación y descripción de sistemas dinámicos no lineales se ha ido consolidando como una técnica eficaz y relativamente rápida gracias al gran desarrollo experimentado en los sistemas de cómputo. Esta técnica de uso común en algunas áreas de la ingeniería aplicada se empezó a utilizar en aplicaciones financieras a mediados de la década de los noventa. El presente trabajo utiliza una de las técnicas más recientes y poderosas en este ámbito: las redes neuronales diferenciales (RND, usada frecuentemente en análisis de procesos de la biotecnología. Mediante esta técnica se lleva a cabo el análisis y la estimación de la evolución del comportamiento del rendimiento del IPC de la Bolsa Mexicana de Valores (BMV durante el periodo comprendido del 8 de noviembre de 1991 al 27 de enero de 2011. Adicionalmente, el análisis incluye un pronóstico intradía (seis valores durante una jornada de operación de la BMV del rendimiento del IPC, el cual tiene una duración de un día después del último dato de la serie de tiempo del IPC. Cabe señalar que los resultados pronosticados mostraron una gran similitud con los datos reales.

  11. variabilite des productions et des revenus des exploitations

    African Journals Online (AJOL)

    3Centre de coopération internationale en recherche agronomique pour le développement (CIRAD), UMR Innovation,. Montpellier, France. Doubangolo COULIBALY, Email kone_b@yahoo.fr. RESUME. La durabilité des systèmes de production à base de coton dans un contexte de variabilité des prix aux producteurs et de ...

  12. APPRIS 2017: principal isoforms for multiple gene sets

    Science.gov (United States)

    Rodriguez-Rivas, Juan; Di Domenico, Tomás; Vázquez, Jesús; Valencia, Alfonso

    2018-01-01

    Abstract The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the ‘principal’ isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants. PMID:29069475

  13. Civili, langue des Baloango

    DEFF Research Database (Denmark)

    Mavoungou, Paul Achille; Ndinga-Koumba-Binza, Hugues Steve

    , Congo, Angola, etc.) issus de la décolonisation. Il présente de façon succincte quelques phénomènes historiques, phonologiques, morphosyntaxiques, homonymiques et analogiques de la langue. Des faits sémantiques des emprunts linguistiques y sont également décrits dans le cadre des changements...

  14. Des racines et des ailes

    Directory of Open Access Journals (Sweden)

    Stéphanie Vincent-Geslin

    2012-05-01

    Full Text Available Les mobilités pendulaires semblent être en augmentation en Europe depuis une dizaine d’années. Cette croissance du temps passé à se déplacer amène à remettre en question la conjecture de Zahavi et apparaît relativement inexplicable en regard du paradigme classique de l’acteur rationnel traditionnellement utilisé dans le champ des transports. Si, dans la littérature, les temps de déplacements sont principalement expliqués par le contexte résidentiel, la forme urbaine et le travail, ce cadre explicatif ne dit rien des processus de décision eux-mêmes qui amènent aux pendularités intensives.À partir d’une enquête qualitative menée auprès de pendulaires français, suisses et belges, cette contribution propose d’analyser les arbitrages et les éléments déterminants des processus de la grande pendularité. Les mobilités quotidiennes pendulaires apparaissent comme le résultat de compromis entre activité professionnelle, attachement résidentiel et choix de vie et prennent ainsi la forme de stratégies de conciliation entre vie privée et vie professionnelle. Ces mobilités spatiales permettent alors paradoxalement la préservation des ancrages résidentiels, sociaux et familiaux.Roots and wings. Long-distance commuting patterns, or how to conciliate professional and personal lifeLong-distance commuting patterns appear to be increasing in Europe over the last ten years. These raising mobility patterns lead to reappraise the Zahavi conjecture and appear largely inexplicable by the classical rational actor paradigm traditionally used in transportation research. In literature, commuting is mainly explained by residential contexts, urban forms and job. Nevertheless this theoretical frame says little about the decision-making processes themselves. Based on a qualitative survey conducted in three European countries - France, Belgium and Switzerland – among a population of high commuters, this paper proposes an analysis of

  15. The Role of Akt Isoforms in Colorectal Cancer

    Science.gov (United States)

    2015-09-01

    AD_________________ Award Number: W81XWH-13-1-0198 TITLE: The Role of Akt Isoforms in Colorectal Cancer PRINCIPAL INVESTIGATOR: Jatin Roper...CONTRACT NUMBER The Role of Akt Isoforms in Colorectal Cancer 5b. GRANT NUMBER W81XWH-13-1-0198 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...substantially reduces colorectal tumorigenesis in our genetically engineered mouse model. We also successfully ablated novel downstream targets of Akt in our

  16. Subpoblaciones neuronales presentes en cultivos primarios de ganglio espinal y su relación con la infección in vitro por virus de rabia

    Directory of Open Access Journals (Sweden)

    Hernán Hurtado

    2000-02-01

    Full Text Available

    El virus de la rabia presenta un fuerte tropismo neuronal y que produce una encefalitis generalmente letal. En un accidente rábico clásico, producido por la mordedura de un animal infectado, el virus es captado por terminaciones nerviosas motoras, autonómicas o sensoriales. Si es captado por estas últimas, el virus se transporta retrógradamente hacia los somas neuronales ubicados en los ganglios espinales y de ahí pasa hasta el Sistema Nervioso Central en donde ejerce su acción patógena. Por este motivo los cultivos de ganglio espinal son un modelo relevante para estudiar la interacción entre el virus de la rabia y las neuronas sensoriales presentes en ellos. En estos cultivos se encuentran dos tipos de células, neuronas y células no neuronales (fibroblastos y células de Schwann. Al inocular los cultivos con virus de rabia cepa CVS (Challenge Virus Standard, a pesar de que las células no neuronales son la mayoría, las que se infectan en mayor proporción son las neuronas, lo que confirma el marcado neurotropismo del virus. Adicionalmente a esto, dentro de la población neuronal, parece existir una subpoblación con mayor susceptibilidad hacia la infección por el virus. Para comprobar esta hipótesis, se caracterizaron las subpoblaciones neuronales presentes en estos cultivos utilizando un criterio morfológico (diámetro neuronal y uno bioquímico (presencia de neuropéptidos como marcadores de subpoblaciones en el ganglio. Se realizó una técnica de doble inmunocitoquímica para virus rábico y los neuropéptidos Sustancia P (SP, Neuropéptido Y (NPY, Galanina (GAL, Péptido Relacionado con el Gen de la Calcitonina (CGRP y Péptido Intestinal Vasoactivo (VIP, que clásicamente se usan para la definición de subpoblaciones. El análisis morfométrico demostró que en nuestros cultivos el 85% de las neuronas presentes son de pequeño diámetro (<25

  17. Characterisation of Cdkl5 transcript isoforms in rat.

    Science.gov (United States)

    Hector, Ralph D; Dando, Owen; Ritakari, Tuula E; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

    2017-03-01

    CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically and experimentally, the rat Cdkl5 gene structure and its associated transcript isoforms. New exonic regions, splice sites and UTRs are described, confirming the presence of four distinct transcript isoforms. The predominant isoform in the brain, which we name rCdkl5_1, is orthologous to the human hCDKL5_1 and mouse mCdkl5_1 isoforms and is the most highly expressed isoform across all brain regions tested. This updated gene model of Cdkl5 in rat provides a framework for studies into its protein products and provides a reference for the development of molecular therapies for testing in rat models of CDKL5 disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes

    DEFF Research Database (Denmark)

    Müller, Margit S; Pedersen, Sofie E; Walls, Anne B

    2015-01-01

    understood. In the present study, we used siRNA-mediated differential knockdown of the two isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform (GPBB), to analyze isoform-specific regulatory characteristics in a cellular setting. Subsequently, we tested the response of each...

  19. Structural diversity and evolution of the N-terminal isoform-specific region of ecdysone receptor-A and -B1 isoforms in insects

    Directory of Open Access Journals (Sweden)

    Kubo Takeo

    2010-02-01

    Full Text Available Abstract Background The ecdysone receptor (EcR regulates various cellular responses to ecdysteroids during insect development. Insects have multiple EcR isoforms with different N-terminal A/B domains that contain the isoform-specific activation function (AF-1 region. Although distinct physiologic functions of the EcR isoforms have been characterized in higher holometabolous insects, they remain unclear in basal direct-developing insects, in which only A isoform has been identified. To examine the structural basis of the EcR isoform-specific AF-1 regions, we performed a comprehensive structural comparison of the isoform-specific region of the EcR-A and -B1 isoforms in insects. Results The EcR isoforms were newly identified in 51 species of insects and non-insect arthropods, including direct-developing ametabolous and hemimetabolous insects. The comprehensive structural comparison revealed that the isoform-specific region of each EcR isoform contained evolutionally conserved microdomain structures and insect subgroup-specific structural modifications. The A isoform-specific region generally contained four conserved microdomains, including the SUMOylation motif and the nuclear localization signal, whereas the B1 isoform-specific region contained three conserved microdomains, including an acidic activator domain-like motif. In addition, the EcR-B1 isoform of holometabolous insects had a novel microdomain at the N-terminal end. Conclusions Given that the nuclear receptor AF-1 is involved in cofactor recruitment and transcriptional regulation, the microdomain structures identified in the isoform-specific A/B domains might function as signature motifs and/or as targets for cofactor proteins that play essential roles in the EcR isoform-specific AF-1 regions. Moreover, the novel microdomain in the isoform-specific region of the holometabolous insect EcR-B1 isoform suggests that the holometabolous insect EcR-B1 acquired additional transcriptional

  20. Differential Signature of the Centrosomal MARK4 Isoforms in Glioma

    Directory of Open Access Journals (Sweden)

    Ivana Magnani

    2011-01-01

    Full Text Available Background: MAP/microtubule affinity-regulating kinase 4 (MARK4 is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs and mouse neural stem cells (NSCs by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker.

  1. Expression of various sarcomeric tropomyosin isoforms in equine striated muscles

    Directory of Open Access Journals (Sweden)

    Syamalima Dube

    2017-06-01

    Full Text Available In order to better understand the training and athletic activity of horses, we must have complete understanding of the isoform diversity of various myofibrillar protein genes like tropomyosin. Tropomyosin (TPM, a coiled-coil dimeric protein, is a component of thin filament in striated muscles. In mammals, four TPM genes (TPM1, TPM2, TPM3, and TPM4 generate a multitude of TPM isoforms via alternate splicing and/or using different promoters. Unfortunately, our knowledge of TPM isoform diversity in the horse is very limited. Hence, we undertook a comprehensive exploratory study of various TPM isoforms from horse heart and skeletal muscle. We have cloned and sequenced two sarcomeric isoforms of the TPM1 gene called TPM1α and TPM1κ, one sarcomeric isoform of the TPM2 and one of the TPM3 gene, TPM2α and TPM3α respectively. By qRT-PCR using both relative expression and copy number, we have shown that TPM1α expression compared to TPM1κ is very high in heart. On the other hand, the expression of TPM1α is higher in skeletal muscle compared to heart. Further, the expression of TPM2α and TPM3α are higher in skeletal muscle compared to heart. Using western blot analyses with CH1 monoclonal antibody we have shown the high expression levels of sarcomeric TPM proteins in cardiac and skeletal muscle. Due to the paucity of isoform specific antibodies we cannot specifically detect the expression of TPM1κ in horse striated muscle. To the best of our knowledge this is the very first report on the characterization of sarcmeric TPMs in horse striated muscle.

  2. Distinct functional interactions between actin isoforms and nonsarcomeric myosins.

    Directory of Open Access Journals (Sweden)

    Mirco Müller

    Full Text Available Despite their near sequence identity, actin isoforms cannot completely replace each other in vivo and show marked differences in their tissue-specific and subcellular localization. Little is known about isoform-specific differences in their interactions with myosin motors and other actin-binding proteins. Mammalian cytoplasmic β- and γ-actin interact with nonsarcomeric conventional myosins such as the members of the nonmuscle myosin-2 family and myosin-7A. These interactions support a wide range of cellular processes including cytokinesis, maintenance of cell polarity, cell adhesion, migration, and mechano-electrical transduction. To elucidate differences in the ability of isoactins to bind and stimulate the enzymatic activity of individual myosin isoforms, we characterized the interactions of human skeletal muscle α-actin, cytoplasmic β-actin, and cytoplasmic γ-actin with human myosin-7A and nonmuscle myosins-2A, -2B and -2C1. In the case of nonmuscle myosins-2A and -2B, the interaction with either cytoplasmic actin isoform results in 4-fold greater stimulation of myosin ATPase activity than was observed in the presence of α-skeletal muscle actin. Nonmuscle myosin-2C1 is most potently activated by β-actin and myosin-7A by γ-actin. Our results indicate that β- and γ-actin isoforms contribute to the modulation of nonmuscle myosin-2 and myosin-7A activity and thereby to the spatial and temporal regulation of cytoskeletal dynamics. FRET-based analyses show efficient copolymerization abilities for the actin isoforms in vitro. Experiments with hybrid actin filaments show that the extent of actomyosin coupling efficiency can be regulated by the isoform composition of actin filaments.

  3. Des Connaissances Aux Politiques

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les synergies ont été mises en commun au fur et à mesure des progrès de la recherche. .... Recherche normative (sur le rôle et la performance des institutions .... Système national d'information sur la gestion environnementale connecté à 19 ...... Un fort contrôle centralisé sur l'élaboration des politiques nationales peut ...

  4. Recognition of faults patterns in electric generators using artificial neurons networks; Reconocimiento de patrones de fallas en generadores electricos empleando redes neuronales artificiales

    Energy Technology Data Exchange (ETDEWEB)

    Rocha Sanchez, Martha Alicia

    1999-03-01

    This work present the development of a reprocessing method to reduce the information of the original data and to maintain the essential information of the data that enter the reduction process. The obtaining of these data is performed with the aid of the ICM ++ (ICMsystems), from which vectors or n-uplos of elements are obtained. This investigation allowed to analyze an evaluation of the paradigms of artificial neural networks, with the intention of detecting which of these paradigms would evolve better with the problem of fault diagnosis in electric generators. From this a prototype system was developed called diagnosis of faults in electrical generators, which automatically will recognize faults in electrical generators by means of the interpretation of the recording of partial discharges. [Spanish] El presente trabajo presenta el desarrollo de un metodo de reprocesamiento para reducir informacion de los datos originales y mantener la informacion esencial de los datos que entran al proceso de reduccion. La obtencion de estos datos se realiza con la ayuda del ICM ++ (ICMsystems), de los cuales se obtienen vectores o n-uplos de elementos. Esta investigacion permitio analizar una evaluacion de los paradigmas de redes neuronales artificiales, con el objeto de detectar cual de estos paradigmas se desempenaria mejor con el problema de diagnostico de fallas en generadores electricos. A partir de esto se desarrollo un sistema prototipo llamado diagnostico de fallas en generadores electricos, el cual automaticamente reconocera fallas en los generadores electricos mediante la interpretacion de registro de descargas parciales.

  5. El compromiso exportador en Colombia: un análisis de redes neuronales || Export Commitment in Colombia: An Analysis of Neural Networks

    Directory of Open Access Journals (Sweden)

    Escandón Barbosa, Diana Marcela

    2017-12-01

    Full Text Available El compromiso exportador suele ser un aspecto empresarial clave para explicar por qué unas empresas exportan más que otras. En este artículo se analizan los determinantes del compromiso exportador en las pymes colombianas desde el punto de vista comportamental y actitudinal mediante un modelo de redes neuronales estimado sobre una muestra de 306 pymes exportadoras. Los resultados permiten concluir que las pymes colombianas se centran en invertir sus recursos financieros propios para impulsar las exportaciones, y la actitud del empresario al riesgo resulta determinante para asumir la actividad exportadora como estrategia empresarial generadora de mayores rendimientos. || The export commitment is often a key to explain why some firms export more than other business aspect. This article discusses the determinants of export commitment in Colombian SMEs from the behavioral and attitudinal viewpoint using a neural network model estimated on a sample of 306 exporting SMEs. The results suggest that Colombian SMEs focus on investing their own resources to boost exports and employers' behavior risks making decisive for export activity as a business strategy that generates higher returns.

  6. Desarrollo de Experimentos de un Robot Navegador con Redes Neuronales en un Ambiente Estructurado: Programación de Conductas con Algoritmo de Retropropagación

    Directory of Open Access Journals (Sweden)

    Alejandro Hossian

    2015-02-01

    Full Text Available El presente artículo busca comunicar los avances realizados en el análisis y desarrollo de experimentos realizados en computadora para robots navegadores mediante la aplicación de Tecnologías Inteligentes. Para su realización se dispone de software y hardware apropiados a partir de los cuales se diseña un ambiente de navegación con obstáculos definidos en el marco de un entorno industrial. En este contexto, se diseña un ambiente computarizado con el cual el robot interactúa, en el cual se desplaza hasta llegar a un objetivo predeterminado, tratando de no colisionar. Bajo estas premisas y requisitos de usuario, se analiza el desempeño del robot a los efectos de procurar optimizar su performance dentro de este escenario. Para evaluar las potencialidades y limitaciones que presentan las conductas del robot, y en función de la complejidad del ambiente de navegación y de las tareas que éste debe llevar a cabo, se hace uso de las tecnologías de las Redes Neuronales Artificiales (RNA. A tal efecto, una arquitectura de RNA de tipo Backpropagation es la que se utiliza en el presente trabajo.

  7. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Goodman, M W; Burstein, E S

    2002-01-01

    The pharmacology of histamine H(3) receptors suggests the presence of distinct receptor isoforms or subtypes. We herein describe multiple, functionally distinct, alternatively spliced isoforms of the human H(3) receptor. Combinatorial splicing at three different sites creates at least six distinct...... receptor isoforms, of which isoforms 1, 2, and 4, encode functional proteins. Detailed pharmacology on isoforms 1 (unspliced receptor), and 2 (which has an 80 amino acid deletion within the third intracellular loop of the protein) revealed that both isoforms displayed robust responses to a series of known...... revealed a rank order of potency at both isoforms of clobenpropit>iodophenpropit>thioperamide, and these drugs are fivefold less potent at isoform 2 than isoform 1. To further explore the pharmacology of H(3) receptor function, we screened 150 clinically relevant neuropsychiatric drugs for H(3) receptor...

  8. Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

    Directory of Open Access Journals (Sweden)

    Fahad Benthani

    2015-05-01

    Full Text Available Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.

  9. Évaluation des pratiques agricoles des légumes feuilles : le cas des ...

    African Journals Online (AJOL)

    SARAH

    30 sept. 2017 ... ... de Biochimie et Immunologie Appliquée, Centre de Recherche en Sciences Biologiques, Alimentaires et .... l'intoxication des agriculteurs et des consommateurs, ... source d'alimentation en eau et au pouvoir d'achat des.

  10. Oxygenation properties and isoform diversity of snake hemoglobins.

    Science.gov (United States)

    Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

    2015-11-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. Copyright © 2015 the American Physiological Society.

  11. Identification and characterization of novel NuMA isoforms

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jin, E-mail: petersdu2112@hotmail.com [Key Laboratory for Cell Proliferation and Regulation of the Ministry of Education, Beijing Normal University, Beijing (China); Xu, Zhe [Department of Clinical Laboratory Diagnosis, Beijing Tiantan Hospital, Capital Medical University, Beijing (China); Core Laboratory for Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing (China); He, Dacheng [Key Laboratory for Cell Proliferation and Regulation of the Ministry of Education, Beijing Normal University, Beijing (China); Lu, Guanting, E-mail: guantlv@126.com [Beijing DnaLead Science and Technology Co., LTD, Beijing (China)

    2014-11-21

    Highlights: • Seven NuMA isoforms generated by alternative splicing were categorized into 3 groups: long, middle and short. • Both exons 15 and 16 in long NuMA were “hotspot” for alternative splicing. • Lower expression of short NuMA was observed in cancer cells compared with nonneoplastic controls. • Distinct localization pattern of short isoforms indicated different function from that of long and middle NuMA. - Abstract: The large nuclear mitotic apparatus (NuMA) has been investigated for over 30 years with functions related to the formation and maintenance of mitotic spindle poles during mitosis. However, the existence and functions of NuMA isoforms generated by alternative splicing remains unclear. In the present work, we show that at least seven NuMA isoforms (categorized into long, middle and short groups) generated by alternative splicing from a common NuMA mRNA precursor were discovered in HeLa cells and these isoforms differ mainly at the carboxyl terminus and the coiled-coil domains. Two “hotspot” exons with molecular mass of 3366-nt and 42-nt tend to be spliced during alternative splicing in long and middle groups. Furthermore, full-length coding sequences of long and middle NuMA obtained by using fusion PCR were constructed into GFP-tagged vector to illustrate their cellular localization. Long NuMA mainly localized in the nucleus with absence from nucleoli during interphase and translocated to the spindle poles in mitosis. Middle NuMA displayed the similar cell cycle-dependent distribution pattern as long NuMA. However, expression of NuMA short isoforms revealed a distinct subcellular localization. Short NuMA were present in the cytosol during the whole cycle, without colocalization with mitotic apparatus. These results have allowed us tentatively to explore a new research direction for NuMA’s various functions.

  12. Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism

    Science.gov (United States)

    Gates, Simon; Miners, John O

    1999-01-01

    Aims The plasma clearance of theobromine (TB; 3,7-dimethylxanthine) is known to be induced in cigarette smokers. To determine whether TB may serve as a model substrate for cytochrome P450 (CYP) 1A2, or possibly other isoforms, studies were undertaken to identify the individual human liver microsomal CYP isoforms responsible for the conversion of TB to its primary metabolites. Methods The kinetics of formation of the primary TB metabolites 3-methylxanthine (3-MX), 7-methylxanthine (7-MX) and 3,7-dimethyluric acid (3,7-DMU) by human liver microsomes were characterized using a specific hplc procedure. Effects of CYP isoform-selective xenobiotic inhibitor/substrate probes on each pathway were determined and confirmatory studies with recombinant enzymes were performed to define the contribution of individual isoforms to 3-MX, 7-MX and 3,7-DMU formation. Results The CYP1A2 inhibitor furafylline variably inhibited (0–65%) 7-MX formation, but had no effect on other pathways. Diethyldithiocarbamate and 4-nitrophenol, probes for CYP2E1, inhibited the formation of 3-MX, 7-MX and 3,7-DMU by ≈55–60%, 35–55% and 85%, respectively. Consistent with the microsomal studies, recombinant CYP1A2 and CYP2E1 exhibited similar apparent Km values for 7-MX formation and CYP2E1 was further shown to have the capacity to convert TB to both 3-MX and 3,7-DMU. Conclusions Given the contribution of multiple isoforms to 3-MX and 7-MX formation and the negligible formation of 3,7-DMU in vivo, TB is of little value as a CYP isoform-selective substrate in humans. PMID:10215755

  13. Functions of PDE3 Isoforms in Cardiac Muscle

    Science.gov (United States)

    Movsesian, Matthew; Ahmad, Faiyaz

    2018-01-01

    Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the isoforms that have been identified in cardiac myocytes; the roles of these enzymes in modulating cAMP-mediated signalling and the processes mediated thereby; and the potential for targeting these enzymes to improve the profile of clinical responses. PMID:29415428

  14. Modulation of neuronal differentiation by CD40 isoforms

    International Nuclear Information System (INIS)

    Hou Huayu; Obregon, Demian; Lou, Deyan; Ehrhart, Jared; Fernandez, Frank; Silver, Archie; Tan Jun

    2008-01-01

    Neuron differentiation is a complex process involving various cell-cell interactions, and multiple signaling pathways. We showed previously that CD40 is expressed and functional on mouse and human neurons. In neurons, ligation of CD40 protects against serum withdrawal-induced injury and plays a role in survival and differentiation. CD40 deficient mice display neuron dysfunction, aberrant neuron morphologic changes, and associated gross brain abnormalities. Previous studies by Tone and colleagues suggested that five isoforms of CD40 exist with two predominant isoforms expressed in humans: signal-transducible CD40 type I and a C-terminal truncated, non-signal-transducible CD40 type II. We hypothesized that differential expression of CD40 isoform type I and type II in neurons may modulate neuron differentiation. Results show that adult wild-type, and CD40 -/- deficient mice predominantly express CD40 type I and II isoforms. Whereas adult wild-type mice express mostly CD40 type I in cerebral tissues at relatively high levels, in age and gender-matched CD40 -/- mice CD40 type I expression was almost completely absent; suggesting a predominance of the non-signal-transducible CD40 type II isoform. Younger, 1 day old wild-type mice displayed less CD40 type I, and more CD40 type II, as well as, greater expression of soluble CD40 (CD40L/CD40 signal inhibitor), compared with 1 month old mice. Neuron-like N2a cells express CD40 type I and type II isoforms while in an undifferentiated state, however once induced to differentiate, CD40 type I predominates. Further, differentiated N2a cells treated with CD40 ligand express high levels of neuron specific nuclear protein (NeuN); an effect reduced by anti-CD40 type I siRNA, but not by control (non-targeting) siRNA. Altogether these data suggest that CD40 isoforms may act in a temporal fashion to modulate neuron differentiation during brain development. Thus, modulation of neuronal CD40 isoforms and CD40 signaling may represent

  15. Alteraciones en la degradación intracelular de proteínas y en la endocitosis en las lipofuscinosis ceroideas neuronales infantil tardía y juvenil

    OpenAIRE

    Vidal Donet, José Manuel

    2014-01-01

    Las lipofuscinosis ceroideas neuronales son un grupo heterogéneo de enfermedades neurodegenerativas hereditarias graves que tienen su inicio en la infancia y que se engloban dentro de las enfermedades de almacenamiento lisosomal. Las características clínicas de estas patologías son una disminución de la capacidad mental acompañada de alteraciones motoras, epilepsia y pérdida de visión. Histológicamente las células muestran una acumulación de material autofluorescente (lipofuscina) en el inte...

  16. Sobre el uso de técnicas chopper para la reducción del ruido flicker en amplificadores para la captación de señales neuronales

    OpenAIRE

    Pérez Prieto, Norberto

    2016-01-01

    La captación de señales neuronales mediante electrodos conectados a circuitos micro-electrónicos es necesaria para aplicaciones clínicas y para el control de prótesis senso-motoras, entre otras muchas aplicaciones bio-médicas. En todas estas aplicaciones, la preservación de la información contenida en las imágenes captadas depende críticamente de las prestaciones de los amplificadores empleados en la cabecera de la cadena de procesamiento electrónica. El problema es que se trata de señales mu...

  17. Opiate addiction : neuronal plasticity on brain reward system and emotional memory-related areas = Adicción a opiáceos : plasticidad neuronal en los circuitos neuronales de recompensa y en áreas de memoria emocional

    OpenAIRE

    García Pérez, Daniel

    2015-01-01

    Los opiáceos, como la morfina, son unos potentes analgésicos que se usan para tratar diversas formas de dolor agudo y crónico. Sin embargo, el uso crónico de opiáceos produce cambios neuroadaptativos a nivel cerebral que conllevan efectos indeseables, como la adicción. La creciente evidencia implica a varios mecanismos de regulación génica (incluyendo epigenéticos, moleculares, celulares y a nivel de circuitos neuronales) en los cambios que las drogas de abuso provocan en el cerebro, siendo e...

  18. Gestion des risques

    CERN Document Server

    Louisot, Jean-Paul

    2009-01-01

    Depuis le début du lie siècle, la gestion des risques connaît une véritable révolution culturelle. Jusqu'alors fonction technique, centrée autour de l'achat de couverture d'assurances, elle est devenue une discipline managériale et transversale : une valise d'instruments que chaque manager doit connaître et appliquer quels que soient son domaine de compétence et ses missions au sein de l'organisation. En effet, la gestion des risques est une culture qui doit être assimilée par chacun des acteurs. C'est précisément l'ambition des 101 questions rassemblées dans cet ouvrage : apporter à chaque manager d'entreprise, de collectivité, d'établissement de santé..., des réponses claires au " pourquoi " et au " comment " : Comment identifier les risques ? Comment analyser les risques ? Quels sont les objectifs de la gestion des risques ? Une carte des risques pour quoi faire ? Pourquoi faut-il financer les risques ? Les entreprises ont-elles des responsabilités pénales ? En quoi consiste la gestion...

  19. La gouvernance des risques naturels et la problematique des ...

    African Journals Online (AJOL)

    Depuis quelques années, la gouvernance des risques naturels dus aux inondations remet en cause les processus de mise en oeuvre des politiques urbaines et la qualité de la structure des aménagements dans les grandes villes du Golfe de Guinée. La perception de la gouvernance et l'application des politiques de ...

  20. The landscape of isoform switches in human cancers

    DEFF Research Database (Denmark)

    Vitting-Seerup, Kristoffer; Sandelin, Albin Gustav

    2017-01-01

    highly predictive of patient survival independent of cancer types. Our data constitute an important resource for cancer researchers, available through interactive web tools. Moreover, our methods, available as an R package, enable systematic analysis of isoform switches from other RNA-seq datasets...

  1. Plectin isoforms as organizers of intermediate filament cytoarchitecture.

    Science.gov (United States)

    Wiche, Gerhard; Winter, Lilli

    2011-01-01

    Intermediate filaments (IFs) form cytoplamic and nuclear networks that provide cells with mechanical strength. Perturbation of this structural support causes cell and tissue fragility and accounts for a number of human genetic diseases. In recent years, important additional roles, nonmechanical in nature, were ascribed to IFs, including regulation of signaling pathways that control survival and growth of the cells, and vectorial processes such as protein targeting in polarized cellular settings. The cytolinker protein plectin anchors IF networks to junctional complexes, the nuclear envelope and cytoplasmic organelles and it mediates their cross talk with the actin and tubulin cytoskeleton. These functions empower plectin to wield significant influence over IF network cytoarchitecture. Moreover, the unusual diversity of plectin isoforms with different N termini and a common IF-binding (C-terminal) domain enables these isoforms to specifically associate with and thereby bridge IF networks to distinct cellular structures. Here we review the evidence for IF cytoarchitecture being controlled by specific plectin isoforms in different cell systems, including fibroblasts, endothelial cells, lens fibers, lymphocytes, myocytes, keratinocytes, neurons and astrocytes, and discuss what impact the absence of these isoforms has on IF cytoarchitecture-dependent cellular functions.

  2. Roles of the troponin isoforms during indirect flight muscle ...

    Indian Academy of Sciences (India)

    IFMs) undergo post-transcriptional and post-translational isoform changes during pupal to adult metamorphosis to meet the high energy and mechanical demands of flight. Using a newly generated Gal4 strain (UH3-Gal4) which is expressed ...

  3. Distinct Functions of Endophilin Isoforms in Synaptic Vesicle Endocytosis

    Directory of Open Access Journals (Sweden)

    Jifeng Zhang

    2015-01-01

    Full Text Available Endophilin isoforms perform distinct characteristics in their interactions with N-type Ca2+ channels and dynamin. However, precise functional differences for the endophilin isoforms on synaptic vesicle (SV endocytosis remain unknown. By coupling RNA interference and electrophysiological recording techniques in cultured rat hippocampal neurons, we investigated the functional differences of three isoforms of endophilin in SV endocytosis. The results showed that the amplitude of normalized evoked excitatory postsynaptic currents in endophilin1 knockdown neurons decreased significantly for both single train and multiple train stimulations. Similar results were found using endophilin2 knockdown neurons, whereas endophilin3 siRNA exhibited no change compared with control neurons. Endophilin1 and endophilin2 affected SV endocytosis, but the effect of endophilin1 and endophilin2 double knockdown was not different from that of either knockdown alone. This result suggested that endophilin1 and endophilin2 functioned together but not independently during SV endocytosis. Taken together, our results indicate that SV endocytosis is sustained by endophilin1 and endophilin2 isoforms, but not by endophilin3, in primary cultured hippocampal neurons.

  4. Molecular characters and expression analysis of a new isoform of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-10-20

    Oct 20, 2008 ... isoform of the myocyte enhancer factor 2 gene from the silkworm, Bombyx mori. Qing-zhi Ling1, 2, ... BMEF2B mRNA content in the brain was measured using the combined method of quantitative RT-PCR and Southern ... specific cofactors to control gene expression in pheno- typically different muscles.

  5. Isoforms of transferrin in psoriasis patients abusing alcohol

    NARCIS (Netherlands)

    P. Hoefkens (Peter); E.M. Higgins; R.J. Ward (Roberta); H.G. van Eijk (Henk)

    1997-01-01

    textabstractThe different isoforms of transferrin have been quantified by isoelectric focusing in the sera of psoriasis patients with and without a history of abusing alcohol. In both male and female psoriasis subjects abusing alcohol, there were significant increases in the

  6. able utilizando redes neuronales artificiales; UTILIZATION OF ARTIFICIAL NEURAL NETWORK IN THE SIMULATION AND CONTROL OF WIND TURBINE GENERATORS WITH VARIABLE SPEED AND VARIABLE PITCH.

    Directory of Open Access Journals (Sweden)

    Osley López González

    2011-02-01

    Full Text Available Con el objetivo de aprovechar al máximo la energía del viento y, a la vez, llevar a cabo un control rápido ypreciso de la potencia máxima suministrada al aumentar la misma se han venido utilizando cada vez mássistemas de control capaces de operar en el punto óptimo de entrega de potencia para determinadosvalores de velocidad del viento y limitarla cuando éste supera su valor máximo. Este sistema de control,considerado en su conjunto, debe responder con la exactitud, estabilidad y rapidez necesaria ante lavariabilidad y aleatoriedad del viento. La relación entre sus variables de salida (velocidad de la turbina ypaso de la pala y la de entrada (velocidad del viento que sea capaz de aprovechar la máxima potenciadisponible en el viento en una zona de trabajo y de limitarla en otra, es altamente complicada puesdepende de factores constructivos y de diseño de la turbina y del generador. Esta característica es muydifícil de representar (sea con el objetivo de simulación o con el de control mediante relacionesfuncionales matemáticas convencionales.En este trabajo los autores proponen representar dicha relaciónmediante la utilización de Redes Neuronales Artificiales entrenadas para ser capaces de responderadecuadamente ante cualquier entrada. Basados en los parámetros y características de un aerogeneradorreal de velocidad y paso variables y utilizando el toolbox de Redes Neuronales del MATLAB SIMULINK losautores obtuvieron un modelo neuronal del sistema de control de la velocidad y el paso de la turbinacomprobando su correcta operación ante diferentes perturbaciones de la red eléctrica mediante estemismo lenguaje de simulación. Se demostró que estas redes pueden ser utilizadas con éxito en lasimulación y el control de este tipo de máquinas en cualquier condición de operación. In order to capture the maximum energy from the wind, control systems operating always at an optimumpower has been utilized. This control system

  7. N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes

    Science.gov (United States)

    Jang, Deok-Jin; Park, Soo-Won; Lee, Jin-A; Lee, Changhoon; Chae, Yeon-Su; Park, Hyungju; Kim, Min-Jeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong-Kiun

    2010-01-01

    Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the…

  8. Photonique des Morphos

    CERN Document Server

    Berthier, Serge

    2010-01-01

    La photonique est déjà présente dans notre vie quotidienne, et on attend maintenant que la manipulation des photons permette aussi le traitement logique des informations. Cependant, l’élément de base qui permet cette manipulation de la lumière, le cristal photonique, est d’une réalisation complexe et mal contrôlée. Dans la course à la maîtrise de la lumière, les structures photoniques naturelles ont beaucoup à nous apprendre. C’est ce que nous montre Serge Berthier qui étudie dans ce livre la structure des écailles des Morphos. Tenant compte de l’essor récent des approches biomimétiques, il présente de manière détaillée plus de dix-huit techniques expérimentales utilisées pour ses analyses, ainsi que les diverses approches théoriques développées pour la modélisation de structures multi-échelles complexes. Première étude quasi-exhaustive des structures fines d’un genre et des propriétés optiques ainsi que colorimétriques générées, ce livre fournit aux entomologiste...

  9. Droit des organisations internationales

    CERN Document Server

    Sorel, Jean-Marc; Ndior, Valère

    2013-01-01

    Cet ouvrage collectif offre aux enseignants et chercheurs en droit international, aux praticiens et aux étudiants, une analyse actualisée du droit des organisations internationales. Il dresse en cinq parties un tableau, illustré par des exemples variés, des problématiques que soulève le phénomène polymorphe d institutionnalisation de la société internationale. La première partie est consacrée au phénomène des « organisations internationales », sous l angle à la fois de l institutionnalisation progressive des relations internationales et de la difficulté à cerner une catégorie unifiée. La deuxième partie rend compte de la création, de la disparition et des mutations des organisations internationales, ici envisagées comme systèmes institutionnels et ordres juridiques dérivés. La troisième partie analyse l autonomie que l acquisition de la personnalité juridique et de privilèges et immunités, un organe administratif intégré, un personnel ou un budget propres confèrent aux organi...

  10. Characterization of ß-Galactosidase Isoforms from Bacillus circulans and Their Contribution to GOS Production

    NARCIS (Netherlands)

    Warmerdam, A.; Paudel, E.; Wanqing, J.; Boom, R.M.; Janssen, A.E.M.

    2013-01-01

    A ß-galactosidase preparation from Bacillus circulans consists of four isoforms called ß-gal-A, ß-gal-B, ß-gal-C, and ß-gal-D. These isoforms differ in lactose hydrolysis and galacto-oligosaccharide (GOS) synthesis at low substrate concentrations. For this reason, using a selection of the isoforms

  11. Aplicación de redes neuronales artificiales y técnicas sig para la predicción de coberturas forestales

    Directory of Open Access Journals (Sweden)

    E. Buendía Rodríguez

    2002-01-01

    Full Text Available En México, como en todo el mundo, se tiene la necesidad de realizar un inventario de sus recursos forestales, a fin de llevar a cabo en forma oportuna y adecuada la planeación y la ejecución de programas de manejo forestal. Un método para la obtención de este tipo de información es a través de modelos de predicción. El presente estudio tiene como objetivo evaluar la habilidad de las redes neuronales artificiales (RNA en la predicción de tipos de coberturas forestales. Las RNA desarrolladas en este trabajo se basaron en información geográfica (altitud, exposición, pendiente, distancia a los escurrimientos, geología y edafología e imágenes de satélite haciendo uso del análisis de componentes principales (acp1, acp2 y acp3, para definir la variable dependiente (vegetación. Esta información fue procesada con una RNA de retropropagación (Backpropagation con dos capas ocultas, con sus respectivas funciones de activación (tangencial hiperbólica y gausiana. Obteniendo una r2=0.8617 para la fase de entrenamiento y una r2=0.8514 en la fase de prueba, alcanzando un 83 % de sitios predichos correctamente, sobrepasando lo alcanzado por otros autores con métodos tradicionales.

  12. One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton

    International Nuclear Information System (INIS)

    Bianchi, Cristina; Torsello, Barbara; Di Stefano, Vitalba; Zipeto, Maria A.; Facchetti, Rita; Bombelli, Silvia; Perego, Roberto A.

    2013-01-01

    The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. Arg promotes actin-based cell protrusions and spreading, and inhibits cell migration by attenuating stress fiber formation and contractility via activation of the RhoA inhibitor, p190RhoGAP, and by regulating focal adhesion dynamics also via CrkII phosphorylation. Eight full-length Arg isoforms with different N- and C-termini are endogenously expressed in human cells. In this paper, the eight Arg isoforms, subcloned in the pFLAG-CMV2 vector, were transfected in COS-7 cells in order to study their subcellular distribution and role in cell morphology, migration and cytoskeletal modulation. The transfected 1BSCTS Arg isoform has a nuclear distribution and phosphorylates CrkII in the nucleus, whilst the other isoforms are detected in the cytoplasm. The 1BLCTL, 1BSCTL, 1ASCTS isoforms were able to significantly decrease stress fibers, induce cell shrinkage and filopodia-like protrusions with a significant increase in p190RhoGAP phosphorylation. In contrast, 1ALCTL, 1ALCTS, 1ASCTL and 1BLCTS isoforms do not significantly decrease stress fibers and induce the formation of retraction tail-like protrusions. The 1BLCTL and 1ALCTL isoforms have different effects on cell migration and focal adhesions. All these data may open new perspectives to study the mechanisms of cell invasiveness. -Highlights: • Each of the eight Arg isoforms was transfected in COS-7 cells. • Only the 1BSCTS Arg isoform has a nuclear distribution in transfected cells. • The cytoplasmic isoforms and F-actin colocalize cortically and in cell protrusions. • Arg isoforms differently phosphorylate p190RhoGAP and CrkII. • Arg isoforms differently modulate stress fibers, cell protrusions and motility

  13. One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Cristina; Torsello, Barbara; Di Stefano, Vitalba; Zipeto, Maria A.; Facchetti, Rita; Bombelli, Silvia; Perego, Roberto A., E-mail: roberto.perego@unimib.it

    2013-08-01

    The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. Arg promotes actin-based cell protrusions and spreading, and inhibits cell migration by attenuating stress fiber formation and contractility via activation of the RhoA inhibitor, p190RhoGAP, and by regulating focal adhesion dynamics also via CrkII phosphorylation. Eight full-length Arg isoforms with different N- and C-termini are endogenously expressed in human cells. In this paper, the eight Arg isoforms, subcloned in the pFLAG-CMV2 vector, were transfected in COS-7 cells in order to study their subcellular distribution and role in cell morphology, migration and cytoskeletal modulation. The transfected 1BSCTS Arg isoform has a nuclear distribution and phosphorylates CrkII in the nucleus, whilst the other isoforms are detected in the cytoplasm. The 1BLCTL, 1BSCTL, 1ASCTS isoforms were able to significantly decrease stress fibers, induce cell shrinkage and filopodia-like protrusions with a significant increase in p190RhoGAP phosphorylation. In contrast, 1ALCTL, 1ALCTS, 1ASCTL and 1BLCTS isoforms do not significantly decrease stress fibers and induce the formation of retraction tail-like protrusions. The 1BLCTL and 1ALCTL isoforms have different effects on cell migration and focal adhesions. All these data may open new perspectives to study the mechanisms of cell invasiveness. -Highlights: • Each of the eight Arg isoforms was transfected in COS-7 cells. • Only the 1BSCTS Arg isoform has a nuclear distribution in transfected cells. • The cytoplasmic isoforms and F-actin colocalize cortically and in cell protrusions. • Arg isoforms differently phosphorylate p190RhoGAP and CrkII. • Arg isoforms differently modulate stress fibers, cell protrusions and motility.

  14. Comparison of Regression and Neural Networks Models to Estimate Solar Radiation Comparación de Regresión y Modelos de Redes Neuronales para Estimar la Radiación Solar

    Directory of Open Access Journals (Sweden)

    Mónica Bocco

    2010-09-01

    Full Text Available The incident solar radiation on soil is an important variable used in agricultural applications; it is also relevant in hydrology, meteorology and soil physics, among others. To estimate this variable, empirical models have been developed using several parameters and, recently, prognostic and prediction models based on artificial intelligence techniques such as neural networks. The aim of this work was to develop linear models and neural networks, multilayer perceptron, to estimate daily global solar radiation and compare their efficiency in its application to a region of the Province of Salta, Argentina. Relative sunshine duration, maximum and minimum temperature, rainfall, binary rainfall and extraterrestrial solar radiation data for the period 1996-2002, were used. All data were supplied by Experimental Station Salta, Instituto Nacional de Tecnología Agropecuaria (INTA, Argentina. For both, neural networks models and linear regressions, three alternative combinations of meteorological parameters were considered. Good results with both prediction methods were obtained, with root mean square error (RMSE values between 1.99 and 1.66 MJ m-2 d-1 for linear regressions and neural networks, and coefficients of correlation (r² between 0.88 and 0.92, respectively. Even though neural networks and linear regression models can be used to predict the daily global solar radiation appropriately, neural networks produced better estimates.La radiación solar incidente en el suelo es una variable importante usada en aplicaciones agronómicas, además es relevante en hidrología, meteorología y física del suelo, entre otros. Para estimarla se han desarrollado modelos empíricos que utilizan distintos parámetros meteorológicos y, recientemente, modelos de pronóstico y predicción basados en técnicas de inteligencia artificial tales como redes neuronales. El objetivo de este trabajo fue desarrollar modelos lineales y de redes neuronales, del tipo perceptr

  15. Santé des adolescents et des jeunes au Burkina Faso : état des ...

    African Journals Online (AJOL)

    Il s'est agi d'une étude évaluative ayant utilisé une revue documentaire associée à une interview des acteurs clés et un atelier de validation et d'identification des interventions pertinentes pour un plan stratégique national. La situation de la santé des adolescents et des jeunes est caractérisée par des grossesses précoces ...

  16. Dental Encounter System (DES)

    Data.gov (United States)

    Department of Veterans Affairs — Dental Encounter System (DES) is an automated health care application designed to capture critical data about the operations of VA Dental Services. Information on...

  17. Diethylstilbestrol (DES) and Cancer

    Science.gov (United States)

    ... DES-exposed grandchildren have? Researchers are also studying possible health effects among women and men who are the children ... for unexposed men. In addition, researchers are studying possible health effects on the grandchildren of mothers who were exposed ...

  18. Table des illustrations

    OpenAIRE

    2016-01-01

    Tableaux Dates d’inauguration des grands hôtels japonais entre 1860 et 1945… 19 Histoire, tourisme et hôtellerie en Corée depuis les années 1870… 59-60 Dates d’inauguration des grands hôtels chinois depuis 1863… 84 Les hôtels de luxe et leurs capacités d’hébergement en Corée en 2000… 103 Les flux de personnes suscités par les hôtels « super luxe » de Séoul en 2000… 105 L’activité des grands hôtels à Séoul en 1999 (en wons)… 106 Propriété et gestion des grands hôtels à Séoul en 1999…. 110 La c...

  19. Direction des Publications

    African Journals Online (AJOL)

    Synthese

    potential and surface properties of their mixtures were investigated, in an ... suppose that the electrostatic repulsive interactions between the two anion ... concentration, et de la conformation des ..... proteins and polysaccharides in solutions,.

  20. La revolution des savants

    CERN Document Server

    Chavanne, A

    1989-01-01

    Premiere cassette : - 1666 : impact de la creation de l'Academie des Sciences par Colbert, trente ans apres le proces de Galile, et au moment des disparitions de Pascal, Descartes et Fermat. Elle dirigee par le hollandais Huyggens jusqu'a sa fuite de France au moment de la revocation de l'Edit de Nantes. - 1750 : l'Encyclopedie (ou "Dictionnaire raisonne des Sciences, des Arts et des Metiers") de Diderot et d'Alembert, soutenus par Malherbes, Buffon, Condorcet et Rousseau. - 1789 : Revolution francaise. - 8 aout 1793 : l'Assemblee, par une declaration de Marat, dissout l'Academie des Sciences. Celle-ci continue cependant ses travaux pour les poids et mesures jusqu'en 1795. - la Terreur : la condamnation a mort, pas au nom d'une "Revolution qui n'a pas besoin de savants" mais pour d'autres raisons, de trois grands hommes de science : Lavoisier, Bailly et Condorcet. - 1793-1794 : Au printemps 93, le Comite de Salut Publique s'inquiete du demi-million de soldats etrangers de toutes les pays frontaliers qui essai...

  1. Isoform expression in the multiple soluble malate dehydrogenase of Hoplias malabaricus (Erythrinidae, Characiformes

    Directory of Open Access Journals (Sweden)

    M. R. Aquino-Silva

    Full Text Available Kinetic properties and thermal stabilities of Hoplias malabaricus liver and skeletal muscle unfractionated malate dehydrogenase (MDH, EC 1.1.1.37 and its isolated isoforms were analyzed to further study the possible sMDH-A* locus duplication evolved from a recent tandem duplication. Both A (A1 and A2 and B isoforms had similar optima pH (7.5-8.0. While Hoplias A isoform could not be characterized as thermostable, B could as thermolabile. A isoforms differed from B isoform in having higher Km values for oxaloacetate. The possibly duplicated A2 isoform showed higher substrate affinity than the A1. Hoplias duplicated A isoforms may influence the direction of carbon flow between glycolisis and gluconeogenesis.

  2. Isoform expression in the multiple soluble malate dehydrogenase of Hoplias malabaricus (Erythrinidae, Characiformes

    Directory of Open Access Journals (Sweden)

    Aquino-Silva M. R.

    2003-01-01

    Full Text Available Kinetic properties and thermal stabilities of Hoplias malabaricus liver and skeletal muscle unfractionated malate dehydrogenase (MDH, EC 1.1.1.37 and its isolated isoforms were analyzed to further study the possible sMDH-A* locus duplication evolved from a recent tandem duplication. Both A (A1 and A2 and B isoforms had similar optima pH (7.5-8.0. While Hoplias A isoform could not be characterized as thermostable, B could as thermolabile. A isoforms differed from B isoform in having higher Km values for oxaloacetate. The possibly duplicated A2 isoform showed higher substrate affinity than the A1. Hoplias duplicated A isoforms may influence the direction of carbon flow between glycolisis and gluconeogenesis.

  3. Nubbin isoform antagonism governs Drosophila intestinal immune homeostasis.

    Directory of Open Access Journals (Sweden)

    Bo G Lindberg

    2018-03-01

    Full Text Available Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila. Global transcriptional profiling of adult flies overexpressing Nub-PB in immunocompetent tissues revealed that this form is a strong transcriptional activator of a large set of immune genes. Further genetic analyses showed that Nub-PB is sufficient to drive expression both independently and in conjunction with nuclear factor kappa B (NF-κB, JNK and JAK/STAT pathways. Similar overexpression of Nub-PD did, conversely, repress expression of the same targets. Strikingly, isoform co-overexpression normalized immune gene transcription, suggesting antagonistic activities. RNAi-mediated knockdown of individual nub transcripts in enterocytes confirmed antagonistic regulation by the two isoforms and that both are necessary for normal immune gene transcription in the midgut. Furthermore, enterocyte-specific Nub-PB expression levels had a strong impact on gut bacterial load as well as host lifespan. Overexpression of Nub-PB enhanced bacterial clearance of ingested Erwinia carotovora carotovora 15. Nevertheless, flies quickly succumbed to the infection, suggesting a deleterious immune response. In line with this, prolonged overexpression promoted a proinflammatory signature in the gut with induction of JNK and JAK/STAT pathways, increased apoptosis and stem cell proliferation. These findings highlight a novel regulatory mechanism of host-microbe interactions mediated by antagonistic

  4. Nitric oxide synthase isoforms in spontaneous and salt hypertension

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

    2007-01-01

    Roč. 25, Suppl. 2 (2007), S 338-S 338 ISSN 0263-6352. [European Meeting on Hypertension /17./. 15.06.2007-19.06.2007, Milan] R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : nitric oxide synthase isoforms * spontaneous and salt hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. Expression of two isoforms of CD44 in human endometrium.

    Science.gov (United States)

    Behzad, F; Seif, M W; Campbell, S; Aplin, J D

    1994-10-01

    The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.

  6. Apolipoprotein (A) Isoform Distribution and Plasma Lipoprotein (a ...

    African Journals Online (AJOL)

    Plasma lipoprotein (a) Concentrations and apo(a) isoforms were determined in 101 healthy Nigerian subjects (M=63), F=38; age range 17-68 years), and coronary heart disease (CHD) patients (M=19, F=17, age range 30-79 years). Median Lp(a) level was 24.4 mg/di in the CHD patients and 22.1 mg/di in the controls.

  7. RON kinase isoforms demonstrate variable cell motility in normal cells.

    Science.gov (United States)

    Greenbaum, Alissa; Rajput, Ashwani; Wan, Guanghua

    2016-09-01

    Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility. Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants. RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03). RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis.

  8. Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

    Science.gov (United States)

    Hector, Ralph D; Dando, Owen; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

    2016-01-01

    Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.

  9. Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

    Directory of Open Access Journals (Sweden)

    Ralph D Hector

    Full Text Available Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5 cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR, which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.

  10. [Characterization of a malic enzyme isoform V from Mucor circinelloides].

    Science.gov (United States)

    Zhang, Yingtong; Chen, Haiqin; Song, Yuanda; Zhang, Hao; Chen, Yongquan; Chen, Wei

    2016-02-04

    We aimed at characterizing a malic enzyme isoform V from Mucor circinelloides. me1 gene encoding malic enzyme isoform V was amplified and cloned into expression vector pET28a. High-purity recombinant protein BLME1 was obtained by affinity chromatography using. Ni-NTA column and characterized subsequently. The optimum conditions were pH at 8.0 and temperature at 33 degrees C. Under optimum conditions, BLME1 activity achieved 92.8 U/mg. The K(m) for L-malate and NADP+ were 0.74960 ± 0.06120 mmol/L and 0.22070 ± 0.01810 mmol/L, the V(max) for L-malate and NADP+ were 72.820 ± 1.077 U/mg and 86.110 ± 1.665 U/mg, respectively. In addition, ions played important roles in BLME1 activity; several ions such as Mn2+, Mg2+, Co2+, Ni2+ could activate BLME1, whereas Ca2+, Cu2+ could be used as inhibitors. Additionally, the metabolic intermediates such as oxaloacetic acid and α-ketoglutaric acid inhibited the activity of BLME1, whereas succinic acid activated it. A malic enzyme isoform V from Mucor circinelloides was characterized, providing the references for further studies on this enzyme.

  11. Differential expression of syndecan isoforms during mouse incisor amelogenesis.

    Science.gov (United States)

    Muto, Taro; Miyoshi, Keiko; Munesue, Seiichi; Nakada, Hiroshi; Okayama, Minoru; Matsuo, Takashi; Noma, Takafumi

    2007-08-01

    Syndecans are transmembranous heparan sulfate proteoglycans (HSPGs) with covalently attached glycosaminoglycan side-chains located on the cell surface. The mammalian syndecan family is composed of four types of syndecans (syndecan-1 to -4). Syndecans interact with the intracellular cytoskeleton through the cytoplasmic domains of their core proteins and membrane proteins, extracellular enzymes, growth factors, and matrix components, through their heparan-sulfate chains, to regulate developmental processes.Here, as a first step to assess the possible roles of syndecan proteins in amelogenesis, we examined the expression patterns of all syndecan isoforms in continuously growing mouse incisors, in which we can overview major differentiation stages of amelogenesis at a glance. Understanding the expression domain of each syndecan isoform during specific developmental stages seems useful for investigating their physiological roles in amelogenesis. Immunohistochemical analysis of syndecan core proteins in the lower incisors from postnatal day 1 mice revealed spatially and temporally specific expression patterns, with syndecan-1 expressed in undifferentiated epithelial and mesenchymal cells, and syndecan-2, -3, and -4 in more differentiated cells. These findings suggest that each syndecan isoform functions distinctly during the amelogenesis of the incisors of mice.

  12. Contribution des radios communautaires a l'education des ...

    African Journals Online (AJOL)

    Contribution des radios communautaires a l'education des populations rurales pour un developpement durable au Benin: etude de cas. ... Journal de la Recherche Scientifique de l'Université de Lomé. Journal Home · ABOUT THIS JOURNAL ...

  13. La convergence des rôles respectifs des relationnistes et des journalistes influence-t-elle la perception qu'ils ont les uns des autres?

    DEFF Research Database (Denmark)

    Valentini, Chiara

    2017-01-01

    la convergence des rôles respectifs des praticiens des relations publiques et des journalistes a un effet favorable sur la perception qu’ils ont les uns des autres. L’effet est plus marqué chez les praticiens des relations publiques, car leur vision de la profession en journalisme correspond à celle...

  14. Promouvoir l'entrepreneuriat inclusif des jeunes et des femmes ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le projet vise à analyser la contribution réelle et potentielle de l'entrepreneuriat inclusif au bien-être des jeunes et des femmes en Côte d'Ivoire, au Burkina Faso et au Kenya. Après un état des lieux de la pratique de l'entrepreneuriat inclusif dans chacun des pays ciblés, l'équipe de recherche étudiera son incidence sur ...

  15. La fabrique des sciences des institutions aux pratiques

    CERN Document Server

    Benninghoff, Martin; Crettaz von Roten, Fabienne; Merz, Martina

    2006-01-01

    Aujourd'hui, les façons de produire, d'organiser, d'évaluer et d'utiliser les savoirs sont en profond débat. De plus en plus, l'Etat, la société civile et l'économie tentent d'influencer les activités des universités et des laboratoires de recherche. Ces développements mettent à l'épreuve tout à la fois les fondements des systèmes d'enseignement supérieur et de recherche, l'autonomie des institutions scientifiques, la définition des frontières des savoirs et l'acceptation des sciences. Dans des contextes suisses et européens, cet ouvrage s'intéresse aux manières dont les sciences et les technologies sont fabriquées, en analysant leurs institutions et les pratiques. A partir d'une approche relationnelle, les sciences et les technologies sont conçues comme des phénomènes profondément sociaux, culturels et politiques. Une telle démarche déstabilise les visions parfois idéalisées et stéréotypées de la construction des savoirs. Des études de cas détaillées décrivent des phénomè...

  16. Effets des extraits vegetaux sur la dynamique de populations des ...

    African Journals Online (AJOL)

    La présente étude se propose de trouver une alternative de l'utilisation des pesticides chimiques en testant l'effet insecticide des extraits aqueux des feuilles de Hyptis suaveolens, graines de Ricinus communis et de Azadirachta indica contre les ravageurs du niébé en conditions de champ en utilisant le cyperméthrine ...

  17. MODELACIÓN DE LA ESTRUCTURA JERÁRQUICA DE MACROINVERTEBRADOS BENTÓNICOS A TRAVÉS DE REDES NEURONALES ARTIFICIALES

    Directory of Open Access Journals (Sweden)

    Claudia Rico

    2009-09-01

    Full Text Available El estudio de la estructura jerárquica de comunidades ecológicas, se ha sintetizado de manera regular a través de técnicas multivariadas de ordenación o clasificación. Sin embargo, al contarse actualmente con herramientas analíticas de computación bioinspirada provenientes de la inteligencia artificial, existe la oportunidad de establecer modelos ecológicos, con características deseables como flexibilidad, exactitud, robustez y confiabilidad. En este contexto, esta investigación utilizó dos métodos computacionales de utilidad en ecoinformática, referidos a redes neuronales artificiales (RNARs para la modelación de la estructura jerárquica de una comunidad de macroinvertebrados bentónicos en términos de auto-organización y predicción. El primer método de modelación consistió en un mapa de auto-organización (MAU, una herramienta de aprendizaje no supervisado que clasificó las especies de macroinvertebrados; este MAU tomó en la capa de entrada la abundancia de cada taxa, y en la de salida proyectó su clasificación en 15 unidades y cuatro agrupamientos jerárquicos. La segunda RNA, correspondió a un Perceptrón multicapa de alimentación adelantada con algoritmo de retropropagación, que modeló separadamente la riqueza y la abundancia de Ephemeroptera, Coleoptera y Trichoptera (ECT, en función de nueve variables fisicoquímicas; la arquitectura del perceptrón correspondió a una constitución de nueve, siete, y una neurona en las capas de entrada, intermedia y salida, respectivamente. Los resultados sugieren que las RNARs utilizadas evidenciaron tanto los patrones jerárquicos, como los de riqueza y abundancia de ECT de manera adecuada, al tiempo que facilitaron el análisis de los datos y el entendimiento de la dinámica de la comunidad de macroinvertebrados, objeto de estudio.

  18. Sistema de servocontrol visual empleando redes neuronales y filtros en el dominio de CIELAB//Visual servo-control system using neural networks and filters based on CIELAB

    Directory of Open Access Journals (Sweden)

    Germán Buitrago Salazar

    2015-05-01

    Full Text Available En este trabajo se presentan los resultados de un sistema servocontrol visual de un brazo robótico de seis grados de libertad. Para esto, se utiliza una red neuronal de tipo feed forward, entrenada por back propagation, para determinar la distancia entre el brazo robótico y un objeto de referencia, que permite ubicarlo en un espacio de trabajo. Las entradas de la red corresponden a la información obtenida de las imágenes capturadas por el Kinect, utilizando un filtro que discrimina la posición de los elementos, en el espacio de color CIELAB (Commission Internationale de l'Eclairage L*a*b components. El resultado de esta investigación demostró que la distancia estimada por la red tiene un margen de error menor, que el algoritmo propuesto en otros trabajos. Igualmente, se probó que el sistema de procesamiento de imágenes es más robusto a ruidos digitales, en comparación con los sistemas que utilizan filtros en el dominio RGB (Red-Green-Blue.Palabras claves: sistema de servocontrol visual, CIELAB, redes neuronales, filtrado de imágenes.______________________________________________________________________________AbstractIn this paper the results of visual servo-control system for a robotic arm with six degrees of freedom are presented. For this purpose, a feed fordward neural network, which was trained by back propagation, is used to determine the distance between the robot arm and a reference object and sitting the robot in the workspace. The inputs of neural network correspond to the information obtained from the images captured by the Kinect, using a filter that discriminates the position of the elements in the CIELAB (Commission Internationale de l'Eclairage L*a*bcomponents color space. The result of this research showed that the estimated distance with the network has an errorless than the algorithm proposed in other works. Similarly, it was proved that the image processing system is more robust to digital noise, compared to

  19. Charte du Conseil des Gouverneurs

    International Development Research Centre (IDRC) Digital Library (Canada)

    Office 2004 Test Drive User

    7. favoriser des communications ouvertes et franches entre le personnel, la direction ..... de dresser le procès-verbal des réunions du Conseil et de ses comités et de veiller à ce ... et des résultats qu'il obtient, et non de sa gestion quotidienne.

  20. Le statut vitaminique des individus et des populations…

    Directory of Open Access Journals (Sweden)

    Icart Jean-Claude

    2000-05-01

    Full Text Available Comme le souligne un récent rapport du Haut comité de santé publique, le statut vitaminique des individus et des populations demeure une question d’actualité. Si les études ne révèlent plus de signes évocateurs de carence, au plus des problèmes de déficiences pour certains groupes à risque, des interrogations, demeurent malgré le contexte d’abondance, concernant la couverture des besoins, laquelle pourrait s’avérer inférieure aux valeurs considérées comme satisfaisantes.

  1. Les lueurs des sables

    CERN Multimedia

    Les lueurs des sables

    2013-01-01

    Two CERN ladies are getting ready for the “Trophée Roses des Sables” rally adventure: Julie and Laetitia are finalizing the last details before setting off on Monday 7th October 2013. Julie from EN-MEF group and Laetitia from DGS-SEE group, met at the CERN Rugby club. This year, they are participating in the 100 % female rally which will take place in Morocco from 10 to 20 October. They will be carrying along 100 kg of humanitarian donation for children such as some clothes, books and medical material. Do not hesitate to show your support at their farewell party to be held on Monday 7 October, from 4 to 6 pm in front of the St Genis-Pouilly Mairie (city Hall). Follow their exciting adventure on the blog leslueursdessables.trophee-roses-des-sables.org and on their association’s Facebook page Les Lueurs des Sables.

  2. Liste des auteurs

    OpenAIRE

    2016-01-01

    Madeleine Akrich      Ecole des Mines – Centre de Sociologie de l’innovation – Paris Noël Barbe      Association comtoise des Arts et Traditions populaires – Besançon Lucien Bernot      Ecole des hautes études en sciences sociales (EHESS) – Paris Anni Borzeix      Centre national de la recherche scientifique (CNRS) –     Groupement d’intérêt public (GIP) « Mutations industrielles » – Paris François Boudarias      Laboratoire d’Anthropologie et de sociologie de Tours (LAST) Dominique Boullier ...

  3. Évaluation des pratiques agricoles des légumes feuilles : le cas des ...

    African Journals Online (AJOL)

    Face à ce constat, le défi de la recherche serait la détermination du niveau actuel de contamination des légumes feuilles et des eaux du barrage et celui de l'État serait l'initiation de programmes de sensibilisation des producteurs par rapport à une gestion plus rigoureuse des pesticides. Mots-clés : pratiques paysannes, ...

  4. ¿Cómo estás atención? Cuáles son y cómo se evalúan las redes neuronales de la atención

    Directory of Open Access Journals (Sweden)

    Fernando Gabriel Luna

    2016-01-01

    Full Text Available Nuestro sistema cognitivo cuenta con redes neuronales que desarrollan diferentes funciones atencionales para afrontar la complejidad estimular del medio ambiente y adaptar nuestro comportamiento a la naturaleza y exigencia de múltiples situaciones. Las redes de la atención conforman un sistema de estructuras cerebrales específicas conectadas y sincronizadas entre sí que nos permiten orientarnos, alertarnos ante algunas señales, sostener nuestra atención, y seleccionar y controlar ciertos estímulos. A continuación se describe la estructura de estas redes, cómo operan en diversas situaciones, y cómo es posible obtener una medida confiable del rendimiento de cada una de las funciones atencionales.

  5. Elaboración de un modelo evolutivo híbrido de algoritmos genéticos y redes neuronales artificiales para dosificaciones de mezclas de concreto reforzadas con fibras metálicas

    Directory of Open Access Journals (Sweden)

    Luis Octavio González Salcedo

    2016-06-01

    Full Text Available En un ambiente computacional, un modelo evolutivo es desarrollado para proponer dosificaciones de mezclas de concretos reforzados con fibras metálicas, para solicitudes de resistencia a la compresión. El modelo es híbrido al incluir un sistema de dosificación basado en algoritmos genéticos y un sistema de estimación de propiedades basado en redes neuronales artificiales. Los resultados obtenidos son comparados con un sistema de dosificaciones reportado experimentalmente. Estas comparaciones muestran una aproximación en el proceso de simulación. Además, por las características del modelo, se considera de aporte en la tecnología del concreto.

  6. Application des TIC à l'atténuation des effets des catastrophes dans ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'Amérique centrale est souvent aux prises avec des inondations et des ... (SIG) et de traitement des images, afin de cartographier les dangers et de modéliser les ... de l'Institut d'étude du développement international de l'Université McGill.

  7. Characterisation of Cdkl5transcript isoforms in rat

    OpenAIRE

    Hector, Ralph D.; Dando, Owen; Ritakari, Tuula E.; Kind, Peter C.; Bailey, Mark E.S.; Cobb, Stuart R.

    2017-01-01

    CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically a...

  8. Overexpression of EMMPRIN Isoform 2 Is Associated with Head and Neck Cancer Metastasis

    OpenAIRE

    Huang, Zhiquan; Tan, Ning; Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

    2014-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and n...

  9. Identification of signals that facilitate isoform specific nucleolar localization of myosin IC

    Energy Technology Data Exchange (ETDEWEB)

    Schwab, Ryan S.; Ihnatovych, Ivanna; Yunus, Sharifah Z.S.A.; Domaradzki, Tera [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States); Hofmann, Wilma A., E-mail: whofmann@buffalo.edu [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States)

    2013-05-01

    Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. In mammalian cells, three isoforms of myosin IC are expressed that differ only in the addition of short isoform-specific N-terminal peptides. Despite the high sequence homology, the isoforms show differences in cellular distribution, in localization to nuclear substructures, and in their interaction with nuclear proteins through yet unknown mechanisms. In this study, we used EGFP-fusion constructs that express truncated or mutated versions of myosin IC isoforms to detect regions that are involved in isoform-specific localization. We identified two nucleolar localization signals (NoLS). One NoLS is located in the myosin IC isoform B specific N-terminal peptide, the second NoLS is located upstream of the neck region within the head domain. We demonstrate that both NoLS are functional and necessary for nucleolar localization of specifically myosin IC isoform B. Our data provide a first mechanistic explanation for the observed functional differences between the myosin IC isoforms and are an important step toward our understanding of the underlying mechanisms that regulate the various and distinct functions of myosin IC isoforms. - Highlights: ► Two NoLS have been identified in the myosin IC isoform B sequence. ► Both NoLS are necessary for myosin IC isoform B specific nucleolar localization. ► First mechanistic explanation of functional differences between the isoforms.

  10. Der Einfluss von COMT Val158Met auf neuronale Korrelate von Delay Discounting bei adulten Patienten mit Aufmerksamkeitsdefizit/Hyperaktivitätsstörung (ADHS)

    OpenAIRE

    Gieseke, Heiner Alexander

    2013-01-01

    In dieser Studie führten 37 adulte Patienten mit einer Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ein Delay Discounting (DD) - Paradigma aus, während gleichzeitig mittels Funktioneller-Nahinfrarotspektroskopie (fNIRS) die Gehirnaktivität der „Regions of Interest“ (ROIs) des Orbitofrontalen-Kortex (OFC) und des Dorsolateralen-Präfrontalen-Kortex (dlPFC) gemessen wurde. Mittels Fragebögen und eines Delay Discounting Tasks (DDT) wurden zusätzlich Verhaltensparameter erhoben und flosse...

  11. NHS-A isoform of the NHS gene is a novel interactor of ZO-1.

    Science.gov (United States)

    Sharma, Shiwani; Koh, Katrina S Y; Collin, Caitlin; Dave, Alpana; McMellon, Amy; Sugiyama, Yuki; McAvoy, John W; Voss, Anne K; Gécz, Jozef; Craig, Jamie E

    2009-08-15

    Mutations in the NHS (Nance-Horan Syndrome) gene lead to severe congenital cataracts, dental defects and sometimes mental retardation. NHS encodes two protein isoforms, NHS-A and -1A that display cell-type dependent differential expression and localization. Here we demonstrate that of these two isoforms, the NHS-A isoform associates with the cell membrane in the presence of intercellular contacts and it immunoprecipitates with the tight junction protein ZO-1 in MDCK (Madin Darby Canine Kidney) epithelial cells and in neonatal rat lens. The NHS-1A isoform however is a cytoplasmic protein. Both Nhs isoforms are expressed during mouse development. Immunolabelling of developing mouse with the anti-NHS antibody that detects both isoforms revealed the protein in the developing head including the eye and brain. It was primarily expressed in epithelium including neural epithelium and certain vascular endothelium but only weakly expressed in mesenchymal cells. In the epithelium and vascular endothelium the protein associated with the cell membrane and co-localized with ZO-1, which indirectly indicates expression of the Nhs-A isoform in these structures. Membrane localization of the protein in the lens vesicle similarly supports Nhs-A expression. In conclusion, the NHS-A isoform of NHS is a novel interactor of ZO-1 and may have a role at tight junctions. This isoform is important in mammalian development especially of the organs in the head.

  12. Prostaglandin D Synthase Isoforms from Cerebrospinal Fluid Vary with Brain Pathology

    Directory of Open Access Journals (Sweden)

    Michael G. Harrington

    2006-01-01

    Full Text Available Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS has been identified in human cerebrospinal fluid and some changes in PTGDS in relation to disease have been reported. However, little is known of the extent that PTGDS isoforms fluctuate across a large range of congenital and acquired diseases. The purpose of this study was to examine changes in PTGDS isoforms in such a population. Spinal fluid from 22 healthy study participants (normal controls with no classifiable neurological or psychiatric diagnosis was obtained and PTGDS isoforms were identified by specific immunostaining and mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in controls consisted of five charge isoforms that were always present and a small number of occasional, low abundance isoforms. A qualitative survey of 98 different people with a wide range of congenital and acquired diseases revealed striking changes. Loss of the control isoforms occurred in congenital malformations of the nervous system. Gain of additional isoforms occurred in some degenerative, most demyelinating and vasculitic diseases, as well as in Creutzfeldt-Jakob disease. A retrospective analysis of published data that quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and Parkinson’s disease compared to controls revealed significant dysregulation. It is concluded that qualitative and quantitative fluctuations of cerebrospinal fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.

  13. Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation.

    Science.gov (United States)

    Dave, Mihika B; Dherai, Alpa J; Udani, Vrajesh P; Hegde, Anaita U; Desai, Neelu A; Ashavaid, Tester F

    2018-01-01

    Transferrin, a major glycoprotein has different isoforms depending on the number of sialic acid residues present on its oligosaccharide chain. Genetic variants of transferrin as well as the primary (CDG) & secondary glycosylation defects lead to an altered transferrin pattern. Isoform analysis methods are based on charge/mass variations. We aimed to compare the performance of commercially available capillary electrophoresis CDT kit for diagnosing congenital disorders of glycosylation with our in-house optimized HPLC method for transferrin isoform analysis. The isoform pattern of 30 healthy controls & 50 CDG-suspected patients was determined by CE using a Carbohydrate-Deficient Transferrin kit. The results were compared with in-house HPLC-based assay for transferrin isoforms. Transferrin isoform pattern for healthy individuals showed a predominant tetrasialo transferrin fraction followed by pentasialo, trisialo, and disialotransferrin. Two of 50 CDG-suspected patients showed the presence of asialylated isoforms. The results were comparable with isoform pattern obtained by HPLC. The commercial controls showed a <20% CV for each isoform. Bland Altman plot showed the difference plot to be within +1.96 with no systemic bias in the test results by HPLC & CE. The CE method is rapid, reproducible and comparable with HPLC and can be used for screening Glycosylation defects. © 2017 Wiley Periodicals, Inc.

  14. REPRISE DES COURS - Yoga

    CERN Multimedia

    Club de Yoga

    2015-01-01

    REPRISE DES COURS – Venez nombreux ! Yoga, Sophrologie, Tai Chi La liste des cours pour le semestre allant du 1er septembre 2015 au 31 janvier 2016 est disponible sur notre site web : http://club-yoga.web.cern.ch Lieu Les cours ont lieu dans la salle des clubs, à l’entresol du restaurant No 2, Bât. 504 (dans la salle no 3 pour la Sophrologie). Prix des cours Le prix pour le semestre (environ 18 leçons) est fixé à 220 CHF plus 10 CHF d’adhésion annuelle au Club. Couple : 200 CHF par personne. 2 cours par semaine : 400 CHF. Inscriptions Les inscriptions aux cours seront prises directement auprès du professeur, lors de la 1ère séance. Avant de s’inscrire pour le semestre, il est possible d’essayer une séance gratuitement. Informations : http://club-yoga.web.cern.ch ----------------------------------------- cern.ch/club-yoga/

  15. Praxis des Klebens

    CERN Document Server

    Theuerkauff, Petra

    1989-01-01

    Bei diesem Buch handelt es sich um einen Leitfaden fur Klebepraktiker. Es werden die verschiedenen Einzelschritte beim kleben beschrieben, als auch die vorbereitenden Massnahmen und anschliessenden Prufverfahren auf Festigkeit behandelt. Das Buch sollte an keinem Arbeitsplatz fehlen, wo man sich mit Problemen der Fugetechnik des Klebens beschaftigt.

  16. Dimensions des stabulations 2018

    OpenAIRE

    Früh, Barbara; Maurer, Veronika; Schneider, Claudia; Schürmann, Stefan; Spengler Neff, Anet; Werne, Steffen

    2018-01-01

    Les «Dimensions des stabulations» contiennent toutes les dimensions pour les stabulations et les parcours pour la production animale en agriculture biologique. Cette liste sert d’instrument de planification pour les éleveurs, d’outil de travail pour la vulgarisation et d’ouvrage de référence pour le contrôle bio.

  17. Direction des Publications

    African Journals Online (AJOL)

    Synthese

    économique des services rendus par les écosystèmes marins. La richesse ... croissance plus rapide que la moyenne de l‟économie ...... services and natural capital. Nature. 387, 253-260. .... d‟interactions où l‟humain est partie prenante. In.

  18. La physique des infinis

    CERN Document Server

    Bernardeau, Francis; Laplace, Sandrine; Spiro, Michel

    2013-01-01

    Écrire l'histoire de l'Univers, tel est l'objectif commun des physiciens des particules et des astrophysiciens. Pour y parvenir, deux approches s'épaulent : la voie de l'infiniment petit, que l'on emprunte via de gigantesques accélérateurs de particules, et celle de l'infiniment grand, dont le laboratoire est l'Univers. Un Univers qui est bien loin d'avoir livré tous ses secrets. On connaît à peine 4,8 % de la matière qui le constitue, le reste étant composé de matière noire (25,8 %) et d'énergie noire (69,4 %), toutes deux de nature inconnue. Et si la récente découverte du boson de Higgs valide le Modèle standard de la physique des particules, celui-ci est toujours incomplet et doit être étendu à ou dépassé. Est-on arrivé au bout du jeu de poupées russes de la matière ? Quelles sont les particules manquantes ? Faut-il revoir les lois fondamentales ? Quels instruments faut-il mettre en œuvre pour accéder à cette « nouvelle physique » ? Comment parler de Super Big Science aux citoye...

  19. A Review of Metallothionein Isoforms and their Role in Pathophysiology

    Directory of Open Access Journals (Sweden)

    Senthil kumar M

    2011-05-01

    Full Text Available Abstract The Metallothionein (MT is a protein which has several interesting biological effects and has been demonstrated increase focus on the role of MT in various biological systems in the past three decades. The studies on the role of MT were limited with few areas like apoptosis and antioxidants in selected organs even fifty years after its discovery. Now acknowledge the exploration of various isoforms of MT such as MT-I, MT-II, MT-III and MT-IV and other isoforms in various biological systems. Strong evidence exists that MT modulates complex diseases and the immune system in the body but the primary function of MT still remains unknown. This review's main objective is to explore the capability to specifically manipulate MT levels in cells and in animals to provide answers regarding how MT could impact those complex disease scenarios. The experimental result mentioned in this review related among MT, zinc, cadmium, diabetic, heart disease, bone retardation, neuro toxicity, kidney dysfunction, cancer, and brain suggest novel method for exploration and contribute significantly to the growing scientist to research further in this field.

  20. Entropy-based model for miRNA isoform analysis.

    Directory of Open Access Journals (Sweden)

    Shengqin Wang

    Full Text Available MiRNAs have been widely studied due to their important post-transcriptional regulatory roles in gene expression. Many reports have demonstrated the evidence of miRNA isoform products (isomiRs in high-throughput small RNA sequencing data. However, the biological function involved in these molecules is still not well investigated. Here, we developed a Shannon entropy-based model to estimate isomiR expression profiles of high-throughput small RNA sequencing data extracted from miRBase webserver. By using the Kolmogorov-Smirnov statistical test (KS test, we demonstrated that the 5p and 3p miRNAs present more variants than the single arm miRNAs. We also found that the isomiR variant, except the 3' isomiR variant, is strongly correlated with Minimum Free Energy (MFE of pre-miRNA, suggesting the intrinsic feature of pre-miRNA should be one of the important factors for the miRNA regulation. The functional enrichment analysis showed that the miRNAs with high variation, particularly the 5' end variation, are enriched in a set of critical functions, supporting these molecules should not be randomly produced. Our results provide a probabilistic framework for miRNA isoforms analysis, and give functional insights into pre-miRNA processing.

  1. Injectabilite des coulis de ciment dans des milieux fissures

    Science.gov (United States)

    Mnif, Thameur

    Le travail presente ici est un bilan du travaux de recherche effectues sur l'injectabilite des coulis de ciment dans lu milieux fissures. Un certain nombre de coulis a base de ciment Portland et microfin ont ete selectionnes afin de caracteriser leur capacite a penetrer des milieux fissures. Une partie des essais a ete menee en laboratoire. L'etude rheologique des differents melanges a permis de tester l'influence de l'ajout de superplastifiant et/ou de fumee de silice sur la distribution granulometrique des coulis et par consequent sur leur capacite a injecter des colonnes de sable simulant un milieu fissure donne. La classe granulometrique d'un coulis, sa stabilite et sa fluidite sont apparus comme les trois facteurs principaux pour la reussite d'une injection. Un facteur de finesse a ete defini au cours de cette etude: base sur la classe granulometrique du ciment et sa stabilite, il peut entrer dans la formulation theorique du debit d'injection avant application sur chantier. La deuxieme et derniere partie de l'etude presente les resultats de deux projets de recherche sur l'injection realises sur chantier. L'injection de dalles de beton fissurees a permis le suivi de l'evolution des pressions avec la distance au point d'injection. L'injection de murs de maconnerie a caractere historique a montre l'importance de la definition de criteres de performance des coulis a utiliser pour traiter un milieu donne et pour un objectif donne. Plusieurs melanges peuvent ainsi etre predefinis et mis a disposition sur le chantier. La complementarite des ciments traditionnels et des ciments microfins devient alors un atout important. Le choix d'utilisation de ces melanges est fonction du terrain rencontre. En conclusion, cette recherche etablit une methodologie pour la selection des coulis a base de ciment et des pressions d'injection en fonction de l'ouverture des fissures ou joints de construction.

  2. Screening phytochimique et identification spectroscopique des ...

    African Journals Online (AJOL)

    Origin

    plante, effectuée pour la première fois, a révélé la présence des alcaloïdes, des flavonoïdes, des tanins catéchiques, des terpènes, des coumarines et des composés cyanogénétiques. Quant aux saponines et les quinones libres, ils sont présents chez les fleurs et absents chez les feuilles. La caractérisation des molécules.

  3. Efficacité des néonicotinoïdes et des pyréthrinoïdes utilisés contre le ...

    African Journals Online (AJOL)

    Efficacité des néonicotinoïdes et des pyréthrinoïdes utilisés contre le foreur des tiges du cacaoyer ( Eulophonotus myrmeleon Felder : Lepidoptera, Cossidae). Implications dans la stratégie de protection de la cacaoculture en Côte d'Ivoire.

  4. Modelo no lineal basado en redes neuronales de unidades producto para clasificación. Una aplicación a la determinación del riesgo en tarjetas de crédito||Non-linear model for classification based on product-unit neural networks. An application to determine credit card risk

    Directory of Open Access Journals (Sweden)

    Martínez-Estudillo, F. J.

    2007-01-01

    Full Text Available El principal objetivo de este trabajo es mostrar un tipo de redes neuronales denominadas redes neuronales basadas en unidades producto (RNUP como un modelo no lineal que puede ser utilizado para la resolución de problemas de clasificación en aprendizaje. Proponemos un método evolutivo en el que simultáneamente se diseña la estructura de la red y se calculan los correspondientes pesos. La metodología que presentamos se basa, por tanto, en la combinación del modelo no lineal RNUP y del algoritmo evolutivo; se aplica a la resolución de un problema de clasificación de índole económica, surgido del mundo de las finanzas. Para evaluar el rendimiento de los modelos de clasificación obtenidos, comparamos nuestra propuesta con varias técnicas clásicas, como la regresión logística o el análisis discriminante, y con el clásico modelo de perceptrón multicapa de redes neuronales basado en unidades sigmoides y el algoritmo de aprendizaje de retropropagación (MLPBP.

  5. Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells.

    Science.gov (United States)

    Béziau, Delphine M; Toussaint, Fanny; Blanchette, Alexandre; Dayeh, Nour R; Charbel, Chimène; Tardif, Jean-Claude; Dupuis, Jocelyn; Ledoux, Jonathan

    2015-01-01

    Phospholipase C (PLC) comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η) based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs) remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA), pulmonary (PA) and middle cerebral arteries (MCA). mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA), δ4 (only expressed in MCA), η1 (expressed in all but MA) and ζ (not detected in any vascular beds tested). The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1) in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found in the

  6. Identification and characterization of novel smoothelin isoforms in vascular smooth muscle.

    Science.gov (United States)

    Krämer, J; Quensel, C; Meding, J; Cardoso, M C; Leonhardt, H

    2001-01-01

    Smoothelin is a cytoskeletal protein specifically expressed in differentiated smooth muscle cells and has been shown to colocalize with smooth muscle alpha actin. In addition to the small smoothelin isoform of 59 kD, we recently identified a large smoothelin isoform of 117 kD. The aim of this study was to identify and characterize novel smoothelin isoforms. The genomic structure and sequence of the smoothelin gene were determined by genomic PCR, RT-PCR and DNA sequencing. Comparison of the cDNA and genomic sequences shows that the small smoothelin isoform is generated by transcription initiation 10 kb downstream of the start site of the large isoform. In addition to the known smoothelin cDNA (c1 isoform) we identified two novel cDNA variants (c2 and c3 isoform) that are generated by alternative splicing within a region, which shows similarity to the spectrin family of F-actin cross-linking proteins. Visceral organs express the c1 form, while the c2 form prevails in well-vascularized tissue as analyzed by RT-PCR. We then generated specific antibodies against the major smoothelin isoforms and could show by Western blotting and immunohistochemistry that the large isoform is specifically expressed in vascular smooth muscle cells, while the small isoform is abundant in visceral smooth muscle. These results strongly suggest that the smoothelin gene contains a vascular and a visceral smooth muscle promoter. The cell-type-specific expression of smoothelin isoforms that are associated with actin filaments may play a role in the modulation of the contractile properties of different smooth muscle cell types. Copyright 2001 S. Karger AG, Basel

  7. Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells.

    Directory of Open Access Journals (Sweden)

    Delphine M Béziau

    Full Text Available Phospholipase C (PLC comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA, pulmonary (PA and middle cerebral arteries (MCA. mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA, δ4 (only expressed in MCA, η1 (expressed in all but MA and ζ (not detected in any vascular beds tested. The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1 in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found

  8. La gestion des résultats des entreprises innovantes

    OpenAIRE

    Dumas, Guillaume

    2014-01-01

    Cette thèse s’intéresse à la gestion des résultats dans le cadre des entreprises innovantes. Elle est constituée de trois articles. Dans le premier, il s’agit d’examiner si les résultats des entreprises innovantes sont gérés et si le stade de développement des innovations influence cette gestion des résultats. Il apparaît que les résultats des entreprises innovantes sont gérés à la hausse. Cette gestion ne semble intervenir qu’au cours de l’activité d’innovation (c’est-à-dire lorsque les entr...

  9. Des dispositions responsables à prendre pour la protection des ...

    African Journals Online (AJOL)

    En considérant l'effet néfaste des maladies, des parasites, du changement climatique et d'autres facteurs environnementaux (les OGM par exemple) sur la survie des abeilles, la baisse de leurs populations dans certaines parties du monde ne saurait être attribuée aux seules pesticides. En plus, l'impact de ces derniers sur ...

  10. Aspects des Onychomycoses chez des patients camerounais de ...

    African Journals Online (AJOL)

    ... biologiques et évolutifs des onychomycoses chez des patients camerounais. Méthode : Il s'agit d'une étude rétrospective et descriptive menée de mars 2011 à mars 2014 dans l'unité de dermatologie de l'hôpital général de Douala (HGD), incluant des patients chez lesquels le diagnostic d'onychomycose avait été posé.

  11. Usages des TIC et socialisation professionnelle des enseignants-chercheurs

    OpenAIRE

    Lavielle-Gutnik, Nathalie; Massou, Luc

    2013-01-01

    En prenant appui sur une nouvelle analyse des données recueillies dans l’enquête Tec-Meus (2008-2011, MSH Lorraine) sur la place accordée par des enseignants-chercheurs en sciences humaines et sociales aux technologies de l’information et de la communication (TIC) dans leur activité d’enseignement, nous souhaitons nous focaliser dans cet article sur la compréhension des processus de socialisation professionnelle en jeu dans leur usage déclaré des TIC. Par socialisation professionnelle, nous e...

  12. Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2.

    Science.gov (United States)

    Peach, Chloe J; Mignone, Viviane W; Arruda, Maria Augusta; Alcobia, Diana C; Hill, Stephen J; Kilpatrick, Laura E; Woolard, Jeanette

    2018-04-23

    Vascular endothelial growth factor-A (VEGF-A) is a key mediator of angiogenesis, signalling via the class IV tyrosine kinase receptor family of VEGF Receptors (VEGFRs). Although VEGF-A ligands bind to both VEGFR1 and VEGFR2, they primarily signal via VEGFR2 leading to endothelial cell proliferation, survival, migration and vascular permeability. Distinct VEGF-A isoforms result from alternative splicing of the Vegfa gene at exon 8, resulting in VEGF xxx a or VEGF xxx b isoforms. Alternative splicing events at exons 5⁻7, in addition to recently identified posttranslational read-through events, produce VEGF-A isoforms that differ in their bioavailability and interaction with the co-receptor Neuropilin-1. This review explores the molecular pharmacology of VEGF-A isoforms at VEGFR2 in respect to ligand binding and downstream signalling. To understand how VEGF-A isoforms have distinct signalling despite similar affinities for VEGFR2, this review re-evaluates the typical classification of these isoforms relative to the prototypical, “pro-angiogenic” VEGF 165 a. We also examine the molecular mechanisms underpinning the regulation of VEGF-A isoform signalling and the importance of interactions with other membrane and extracellular matrix proteins. As approved therapeutics targeting the VEGF-A/VEGFR signalling axis largely lack long-term efficacy, understanding these isoform-specific mechanisms could aid future drug discovery efforts targeting VEGF receptor pharmacology.

  13. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    Science.gov (United States)

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases.

  14. Direction des Publications

    African Journals Online (AJOL)

    Synthese

    Unité de Recherche des Matériaux et des Energies Renouvelables (U.R.M.E.R). Université Abou –Baker Belkaid B.p : 119 Tlemcen 13000 Algerie. 2. Unité de Développement de la Technologie Du Silicium. UDTS, BP 399, Alger, Algérie. Accepté le : 08/06/2011. صخلم. داوﻣﻟا نﻣ ﻲﺗﻟا ﺔﺻﺎﺧو ،ﺔﻋﺎﻧﺻ يأ رﯾوطﺗ ﻲﻓ ﺎﯾﺳﯾﺋر ﻼﻣﺎﻋ ةرﯾﺧﻷا تاوﻧﺳﻟا ...

  15. Mykotische Infektionen des Penis

    Directory of Open Access Journals (Sweden)

    Mayser P

    1999-01-01

    Full Text Available Die häufigste mykotische Infektion des Penis stellt die Balanitis/Balonoposthitis durch Candida albicans dar. Sie weist eine steigende Inzidenz auf und scheint vornehmlich durch Genitalverkehr übertragen zu werden. Penile Infektionen durch Dermatophyten sind sehr selten, obwohl die Tinea inguinalis zu den häufigeren Erkrankungen zählt. Eine Mitbeteiligung des Penis im Rahmen von Systemmykosen kennzeichnet zumeist ein schwer verlaufende Erkrankung. Ursächlich kann beim immunoinkompetenten Patienten nahezu jeder Erreger in Frage kommen. Biopsie sowie Gewebekultur aus den meist ulzerativen Veränderungen können die Diagnose sichern. Die meisten superfiziellen Infektionen sprechen zufriedenstellend auf eine topische antimykotische Behandlung an, insbesondere wenn Provokationsfaktoren und die Möglichkeit der sexuellen Transmission berücksichtigt werden. Ausgedehnte Infektionen durch Dermatophyten, Hefen und natürlich systemische Infektionen erfordern eine systemische antimykotische Therapie.

  16. Chimie des processus biologiques

    OpenAIRE

    Fontecave, Marc

    2014-01-01

    Cours : Chimie biologique radicalaire : de l’origine de l’ADN au métabolisme d’aujourd’hui Il est généralement admis que les radicaux libres, espèces chimiques très réactives, sont des poisons pour les systèmes vivants qui ont élaboré des mécanismes efficaces pour s’en protéger et s’en débarrasser lorsqu’ils viennent à se former, par accident. Par exemple ce qu’on appelle communément le stress oxydant est une situation caractérisée par une accumulation de radicaux issus de l’oxygène moléculai...

  17. RAGE receptor and its soluble isoforms in diabetes mellitus complications

    Directory of Open Access Journals (Sweden)

    Mauren Isfer Anghebem Oliveira

    2013-04-01

    Full Text Available Chronic hyperglycemia, which is present in all types of diabetes, increases the formation of advanced glycation end-products (AGEs. The interaction of AGEs with receptor of advanced glycation end-products (RAGE initiates a cascade of pro-inflammatory and pro-coagulant processes that result in oxidative stress, stimulating the formation and accumulation of more AGE molecules. This cyclic process, denominated metabolic memory, may explain the persistency of diabetic vascular complications in patients with satisfactory glycemic control. The RAGE found in several cell membranes is also present in soluble isoforms (esRAGE and cRAGE, which are generated by alternative deoxyribonucleic acid splicing or by proteolytic cleavage. This review focuses on new research into these mediators as potential biomarkers for vascular complications in diabetes.

  18. Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions.

    Science.gov (United States)

    Wojtczak, Beata; Pula, Bartosz; Gomulkiewicz, Agnieszka; Olbromski, Mateusz; Podhorska-Okolow, Marzena; Domoslawski, Paweł; Bolanowski, Marek; Daroszewski, Jacek; Dziegiel, Piotr

    2017-09-01

    Metallothioneins (MTs) are involved in numerous cell processes such as binding and transport of zinc and copper ions, differentiation, proliferation and apoptosis, therefore contributing to carcinogenesis. Scarce data exist on their expression in benign and malignant lesions of the thyroid. mRNA expression of functional isoforms of MT genes (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT4) was studied in 17 nodular goiters (NG), 12 follicular adenomas (FA) and 26 papillary thyroid carcinomas (PTC). One-way ANOVA revealed significant differences in mRNA expression levels of MT1A (pbenign and malignant lesions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. La cogestion des Ressources naturelles

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'eau, le sol, les nutriments, la lumière du soleil — ce sont des choses de la vie. .... habitent encore ces régions, soit de 9 % à 14 % de la population mondiale. ...... La guerre civile a fait vivre au Cambodge des années de chaos, d'anarchie et ...... et les allégeances politiques sont des facteurs qu'il est impossible d'ignorer.

  20. Des Ogle's old stump

    International Nuclear Information System (INIS)

    Jones, M.; Sutton, D.; Wallace, R.

    1998-01-01

    On 17 October 1997 Sylvia Bryan of RD4 Kaitaia wrote to 'Dear Somebody-Everybody' at the Anthropology Department, University of Auckland, urging further examination of an adzed stump found by Des Ogle during planting out of the Te Aupouri forest. The authors have since sought out relevant information and present it here for the interests of our readers. (author). 7 refs., 1 fig

  1. Troponin T isoform expression is modulated during Atlantic Halibut metamorphosis

    Directory of Open Access Journals (Sweden)

    Llewellyn Lynda

    2007-06-01

    Full Text Available Abstract Background Flatfish metamorphosis is a thyroid hormone (TH driven process which leads to a dramatic change from a symmetrical larva to an asymmetrical juvenile. The effect of THs on muscle and in particular muscle sarcomer protein genes is largely unexplored in fish. The change in Troponin T (TnT, a pivotal protein in the assembly of skeletal muscles sarcomeres and a modulator of calcium driven muscle contraction, during flatfish metamophosis is studied. Results In the present study five cDNAs for halibut TnT genes were cloned; three were splice variants arising from a single fast TnT (fTnT gene; a fourth encoded a novel teleost specific fTnT-like cDNA (AfTnT expressed exclusively in slow muscle and the fifth encoded the teleost specific sTnT2. THs modified the expression of halibut fTnT isoforms which changed from predominantly basic to acidic isoforms during natural and T4 induced metamorphosis. In contrast, expression of red muscle specific genes, AfTnT and sTnT2, did not change during natural metamorphosis or after T4 treatment. Prior to and after metamorphosis no change in the dorso-ventral symmetry or temporal-spatial expression pattern of TnT genes and muscle fibre organization occurred in halibut musculature. Conclusion Muscle organisation in halibut remains symmetrical even after metamorphosis suggesting TH driven changes are associated with molecular adaptations. We hypothesize that species specific differences in TnT gene expression in teleosts underlies different larval muscle developmental programs which better adapts them to the specific ecological constraints.

  2. Grundlagen des Tissue Engineering

    Science.gov (United States)

    Mayer, Jörg; Blum, Janaki; Wintermantel, Erich

    Die Organtransplantation stellt eine verbreitete Therapie dar, um bei krankheitsoder unfallbedingter Schädigung eines Organs die Gesamtheit seiner Funktionen wieder herzustellen, indem es durch ein Spenderorgan ersetzt wird. Organtransplantationen werden für die Leber, die Niere, die Lunge, das Herz oder bei schweren grossflächigen Verbrennungen der Haut vorgenommen. Der grosse apparative, personelle und logistische Aufwand und die Risiken der Transplantationschirurgie (Abstossungsreaktionen) sowie die mangelnde Verfügbarkeit von immunologisch kompatiblen Spenderorganen führen jedoch dazu, dass der Bedarf an Organtransplantaten nur zu einem sehr geringen Teil gedeckt werden kann. Sind Spenderorgane nicht verfügbar, können in einzelnen Fällen lebenswichtige Teilfunktionen, wie beispielsweise die Filtrationsfunktion der Niere durch die Blutreinigung mittels Dialyse ersetzt oder, bei mangelnder Funktion der Bauchspeicheldrüse (Diabetes), durch die Verabreichung von Insulin ein normaler Zustand des Gesamtorganismus auch über Jahre hinweg erhalten werden. Bei der notwendigen lebenslangen Anwendung apparativer oder medikamentöser Therapie können für den Patienten jedoch häufig schwerwiegende, möglicherweise lebensverkürzende Nebenwirkungen entstehen. Daher werden in der Forschung Alternativen gesucht, um die Funktionen des ausgefallenen Organs durch die Implantation von Zellen oder in vitro gezüchteten Geweben möglichst umfassend wieder herzustellen. Dies erfordert biologisch aktive Implantate, welche die für den Stoffwechsel des Organs wichtigen Zellen enthalten und einen organtypischen Stoffwechsel entfalten.

  3. Dictionnaire des risques psychosociaux

    CERN Document Server

    Zawieja, Philippe

    2014-01-01

    Stress, suicide, harcèlement, épuisement professionnel, workaholism... Au-delà de la souffrance qu'elles désignent, ces notions souvent récentes constituent une approche inédite, et demandent à mieux être comprises, dans leur ensemble et isolément. C'est tout l'enjeu de ce dictionnaire, pionnier en son genre. Le lecteur y trouvera représentés, avec les 314 entrées (rédigées par 251 contributeurs) qui le composent, tous les champs disciplinaires s'intéressant à la souffrance au travail : psychologie du travail et des organisations, psychologie sociale et psychosociologie, psychanalyse, psychopathologie et psychiatrie, ergonomie, sociologie du travail et des organisations, médecine du travail, droit du travail et de la sécurité sociale, sciences de gestion, philosophie... Y sont détaillés les principaux concepts, notions, approches, méthodes, théories, outils, études, etc., ayant cours dans l'étude des risques psychosociaux, mais aussi certaines professions emblématiques (infirmières,...

  4. Le vernis des apparences

    Directory of Open Access Journals (Sweden)

    Grazia Nicosia

    2010-04-01

    Full Text Available Le but de cet article est de comprendre l’incidence sémiotique du nettoyage d’un tableau ainsi que la résultante cognitive induite sur l’observateur. Cette étude confronte l’analyse des phénomènes visuels engendrés par le jaunissement du vernis et son retrait, à des entretiens réalisés à dessein. Le retrait d’un vernis jauni change considérablement l’image. L’heure, le climat, la saison et l’activité même des personnages s’en trouvent ainsi modifié. La patine peut être perçue, soit comme un obstacle à l’exploration, soit pour ceux qui l’apprécient, comme le medium d’une relation plus intime entre l’œuvre et l’observateur.The purpose of this article is to understand the semiotic impact of the cleaning of a painting and the cognitive effects induced on the observer. This study analyses conjointly the visual phenomenon generated by yellowing varnish and its removal and controlled interviews of observers.The removal of yellowing varnish modifies considerably the perception of the picture. Daytime, climate, season and characters activities are modified. The patina may be perceived either as an obstacle to the painting exploration, or, for those who appreciate it, as a medium for a closer relationship between the painting and the observer.

  5. Harmonische Reduktion des linken Ventrikels

    OpenAIRE

    Atila, M. (Mehmet)

    2005-01-01

    In der vorliegenden Arbeit wurde die harmonische Reduktion des linken Ventrikels am Modell des ausgewachsenen Hausschweins, unter Verwendung von Saugkappen variabler Größe untersucht. In 10 Schweinen mit Herzen normaler Größe und Funktion wurde eine Saugkappe, in Größe und Form an das abzufaltende Wandsegment angepasst, auf die epikardiale Oberfläche des schlagenden Herzens gesetzt. Wir führten Messungen der linksventrik. und der pulmonalart. Drücke, des ventrikulären Durchmessers und der Her...

  6. Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies

    Directory of Open Access Journals (Sweden)

    Heger Christopher D

    2010-12-01

    Full Text Available Abstract Background Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers. Methods Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses. Results We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76% of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72% and 27% had only low levels of expression. Conclusions Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in

  7. La recherche en action : des solutions locales, des effets durables ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    15 déc. 2010 ... Le Centre de recherches pour le développement international (CRDI) appuie la production et l'application de connaissances qui améliorent de façon notable la situation des habitants des pays en développement.

  8. Analyse des caractéristiques structurelles et des performances ...

    African Journals Online (AJOL)

    SARAH

    28 févr. 2014 ... performances technico-économiques de la riziculture irriguée en Côte d' .... en nous basant sur les prix des intrants et des produits en vigueur au cours ..... la recherche et de la vulgarisation et le transfert de technologies ; (2) ...

  9. Evaluation des pratiques de gestion des adventices en riziculture

    African Journals Online (AJOL)

    Les résultats ont montré que les méthodes de gestion de l'enherbement ont .... Le contrôle des adventices en riziculture irriguée a principalement .... mesurer la hauteur des plantes et la longueur ..... Performance agronomique du Sys- tème de ...

  10. Diversification des moyens de subsistance des petits producteurs de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'économie du Malawi repose essentiellement sur la culture du tabac, qui représente plus de 70 % des revenus d'exportation. Pour 60 % des 100 000 membres de la National Smallholder Farmers' Association of Malawi (NASFAM), le tabac est la seule et unique source de revenus. Les cultivateurs de tabac, au Malawi ...

  11. Culture du bambou : diversification des moyens de subsistance des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Culture du bambou : diversification des moyens de subsistance des petits producteurs de tabac du sud de la province de Nyanza, au Kenya - phase II. Au cours de la première phase du projet (projet no 103765), les chercheurs ont effectué une analyse de marché pour le bambou et les produits du bambou, comparé les ...

  12. Roles et taches des accompagnateurs des patients hospitalises ...

    African Journals Online (AJOL)

    Roles et taches des accompagnateurs des patients hospitalises dans le service de pneumo-phtysiologie au Centre Hospitalier Universitaire Yalgado Ouedraogo de ... Logistical support represented by material support, drug supply, cleaning of premises, and littering occupied respectively 100%, 91%, 42% and 73%.

  13. Glycosylation differences contribute to distinct catalytic properties among bone alkaline phosphatase isoforms.

    Science.gov (United States)

    Halling Linder, Cecilia; Narisawa, Sonoko; Millán, José Luis; Magnusson, Per

    2009-11-01

    Three circulating human bone alkaline phosphatase (BALP) isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue. The present study was designed to correlate differing glycosylation patterns of each BALP isoform with their catalytic activity towards presumptive physiological substrates and to compare those properties with two recombinant isoforms of the tissue-nonspecific ALP (TNALP) isozyme, i.e., TNALP-flag, used extensively for mutation analysis of hypophosphatasia mutations and sALP-FcD(10), a chimeric enzyme recently used as therapeutic drug in a mouse model of infantile hypophosphatasia. The BALP isoforms were prepared from human osteosarcoma (SaOS-2) cells and the kinetic properties were evaluated using the synthetic substrate p-nitrophenylphosphate (pNPP) at pH 7.4 and 9.8, and the three suggested endogenous physiological substrates, i.e., inorganic pyrophosphate (PP(i)), pyridoxal 5'-phosphate (PLP), and phosphoethanolamine (PEA) at pH 7.4. Qualitative glycosylation differences were also assessed by lectin binding and precipitation. The k(cat)/K(M) was higher for B2 for all the investigated substrates. The catalytic activity towards PEA was essentially undetectable. The kinetic activity for TNALP-flag and sALP-FcD(10) was similar to the activity of the human BALP isoforms. The BALP isoforms differed in their lectin binding properties and dose-dependent lectin precipitation, which also demonstrated differences between native and denatured BALP isoforms. The observed differences in lectin specificity were attributed to N-linked carbohydrates. In conclusion, we demonstrate significantly different catalytic properties among the BALP isoforms due to structural differences in posttranslational glycosylation. Our data also suggests that PEA is not an endogenous substrate for the BALP isoforms or for the recombinant TNALP isoforms. The TNALP

  14. Inulin isoforms differ by repeated additions of one crystal unit cell

    Science.gov (United States)

    Cooper, Peter D.; Barclay, Thomas G.; Ginic-Markovic, Milena; Gerson, Andrea R.; Petrovsky, Nikolai

    2014-01-01

    Inulin isoforms, especially delta inulin, are important biologically as immune activators and clinically as vaccine adjuvants. In exploring action mechanisms, we previously found regular increments in thermal properties of the seven-member inulin isoform series that suggested regular additions of some energetic structural unit. Because the previous isolates carried additional longer chains that masked defining ranges, these were contrasted with new isoform isolates comprising only inulin chain lengths defining that isoform. The new series began with 19 fructose units per chain (alpha-1 inulin), increasing regularly by 6 fructose units per isoform. Thus the ‘energetic unit’ equates to 6 fructose residues per chain. All isoforms showed indistinguishable X-ray diffraction patterns that were also identical with known inulin crystals. We conclude that an ‘energetic unit’ equates to one helix turn of 6 fructose units per chain as found in one unit cell of the inulin crystal. Each isoform chain comprised progressively more helix turns plus one additional fructose and glucose residues per chain. PMID:24528745

  15. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  16. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  17. Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

    Directory of Open Access Journals (Sweden)

    Lijun Catherine Liu

    2016-09-01

    Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

  18. High Molecular Weight Isoforms of Growth Hormone In Cells of the Immune System

    Science.gov (United States)

    Weigent, Douglas A.

    2013-01-01

    A substantial body of research exists to support the idea that cells of the immune system produce growth hormone (GH). However, the structure and mechanism of action of lymphocyte-derived GH continues to remain largely unknown. Here we present the results of Western analysis of whole cell extracts showing that different molecular weight isoforms of GH of approximately 100 kDa, 65 kDa, and 48 kDa can be detected in primary mouse cells of the immune system and in the mouse EL4 cell line. The identity of the 65 kDa and 48 kDa isoforms of GH were confirmed by mass spectrometry. The various isoforms were detected in both enriched T and B spleen cell populations. The large molecular weight isoform appears to reside primarily in the cytoplasm whereas the lower molecular weight 65 kDa and 48 kDa isoforms were detected primarily in the nucleus. These results also suggest that GH isoforms are induced by oxidative stress. In EL4 cells overexpressing GH, the expression of luciferase controlled by a promoter containing the antioxidant response element is increased almost three-fold above control. The data suggest that the induction of isoforms of the GH molecule in cells of the immune system may be an important mechanism of adaptation and/or protection of lymphoid cells under conditions of oxidative stress. PMID:21741628

  19. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes.

    Science.gov (United States)

    Müller, Margit S; Pedersen, Sofie E; Walls, Anne B; Waagepetersen, Helle S; Bak, Lasse K

    2015-01-01

    Glycogen phosphorylase (GP) is activated to degrade glycogen in response to different stimuli, to support both the astrocyte's own metabolic demand and the metabolic needs of neurons. The regulatory mechanism allowing such a glycogenolytic response to distinct triggers remains incompletely understood. In the present study, we used siRNA-mediated differential knockdown of the two isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform (GPBB), to analyze isoform-specific regulatory characteristics in a cellular setting. Subsequently, we tested the response of each isoform to phosphorylation, triggered by incubation with norepinephrine (NE), and to AMP, increased by glucose deprivation in cells in which expression of one GP isoform had been silenced. Successful knockdown was demonstrated on the protein level by Western blot, and on a functional level by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE, with glycogen levels significantly reduced only after 60 min. In contrast, allosteric activation of GP by AMP, induced by glucose deprivation, seemed to mainly affect GPBB, as only knockdown of GPBB, but not of GPMM, delayed the glycogenolytic response to glucose deprivation. Our results indicate that the two GP isoforms expressed in astrocytes respond to different physiological triggers, therefore conferring distinct metabolic functions of brain glycogen. © 2014 Wiley Periodicals, Inc.

  20. Utilisation sans risque des eaux usées, des excréta et des eaux ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les responsables de ce projet piloteront l'application et l'adaptation des principes directeurs relatifs à l'utilisation sans risque des eaux usées, des excreta et des eaux grises en agriculture et en aquaculture (Guidelines for the Safe Use of Wastewater, Excreta and Greywater in Agriculture and Aquaculture), que ...

  1. Myosin isoform fiber type and fiber size in the tail of the Virginia opossum (Didelphis virginiana).

    Science.gov (United States)

    Hazimihalis, P J; Gorvet, M A; Butcher, M T

    2013-01-01

    Muscle fiber type is a well studied property in limb muscles, however, much less is understood about myosin heavy chain (MHC) isoform expression in caudal muscles of mammalian tails. Didelphid marsupials are an interesting lineage in this context as all species have prehensile tails, but show a range of tail-function depending on either their arboreal or terrestrial locomotor habits. Differences in prehensility suggest that MHC isoform fiber types may also be different, in that terrestrial opossums may have a large distribution of oxidative fibers for object carrying tasks instead of faster, glycolytic fiber types expected in mammals with long tails. To test this hypothesis, MHC isoform fiber type and their regional distribution (proximal/transitional/distal) were determined in the tail of the Virginia opossum (Didelphis virginiana). Fiber types were determined by a combination of myosin-ATPase histochemistry, immunohistochemistry, and SDS-PAGE. Results indicate a predominance of the fast MHC-2A and -2X isoforms in each region of the tail. The presence of two fast isoforms, in addition to the slow MHC-1 isoform, was confirmed by SDS-PAGE analysis. The overall MHC isoform fiber type distribution for the tail was: 25% MHC-1, 71% MHC-2A/X hybrid, and 4% MHC-1/2A hybrid. Oxidative MHC-2A/X isoform fibers were found to be relatively large in cross-section compared to slow, oxidative MHC-1 and MHC-1/2A hybrid fibers. A large percentage of fast MHC-2A/X hybrids fibers may be suggestive of an evolutionary transition in MHC isoform distribution (fast-to-slow fiber type) in the tail musculature of an opossum with primarily a terrestrial locomotor habit and adaptive tail-function. Copyright © 2012 Wiley Periodicals, Inc.

  2. Detection of VEGF-A(xxx)b isoforms in human tissues.

    Science.gov (United States)

    Bates, David O; Mavrou, Athina; Qiu, Yan; Carter, James G; Hamdollah-Zadeh, Maryam; Barratt, Shaney; Gammons, Melissa V; Millar, Ann B; Salmon, Andrew H J; Oltean, Sebastian; Harper, Steven J

    2013-01-01

    Vascular Endothelial Growth Factor-A (VEGF-A) can be generated as multiple isoforms by alternative splicing. Two families of isoforms have been described in humans, pro-angiogenic isoforms typified by VEGF-A165a, and anti-angiogenic isoforms typified by VEGF-A165b. The practical determination of expression levels of alternative isoforms of the same gene may be complicated by experimental protocols that favour one isoform over another, and the use of specific positive and negative controls is essential for the interpretation of findings on expression of the isoforms. Here we address some of the difficulties in experimental design when investigating alternative splicing of VEGF isoforms, and discuss the use of appropriate control paradigms. We demonstrate why use of specific control experiments can prevent assumptions that VEGF-A165b is not present, when in fact it is. We reiterate, and confirm previously published experimental design protocols that demonstrate the importance of using positive controls. These include using known target sequences to show that the experimental conditions are suitable for PCR amplification of VEGF-A165b mRNA for both q-PCR and RT-PCR and to ensure that mispriming does not occur. We also provide evidence that demonstrates that detection of VEGF-A165b protein in mice needs to be tightly controlled to prevent detection of mouse IgG by a secondary antibody. We also show that human VEGF165b protein can be immunoprecipitated from cultured human cells and that immunoprecipitating VEGF-A results in protein that is detected by VEGF-A165b antibody. These findings support the conclusion that more information on the biology of VEGF-A165b isoforms is required, and confirm the importance of the experimental design in such investigations, including the use of specific positive and negative controls.

  3. The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

    Science.gov (United States)

    Cooper, Peter D; Barclay, Thomas G; Ginic-Markovic, Milena; Petrovsky, Nikolai

    2013-01-01

    In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) “melting” or “freezing” points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators. PMID:23853206

  4. Learning-dependent gene expression of CREB1 isoforms in the molluscan brain

    Directory of Open Access Journals (Sweden)

    Hisayo Sadamoto

    2010-05-01

    Full Text Available Cyclic AMP-responsive element binding protein1 (CREB1 has multiple functions in gene regulation. Various studies have reported that CREB1-dependent gene induction is necessary for memory formation and long-lasting behavioral changes in both vertebrates and invertebrates. In the present study, we characterized Lymnaea CREB1 (LymCREB1 mRNA isoforms of spliced variants in the central nervous system (CNS of the pond snail Lymnaea stagnalis. Among these spliced variants, the three isoforms that code a whole LymCREB1 protein are considered to be the activators for gene regulation. The other four isoforms, which code truncated LymCREB1 proteins with no kinase inducible domain, are the repressors. For a better understanding of the possible roles of different LymCREB1 isoforms, the expression level of these isoform mRNAs was investigated by a real-time quantitative RT-PCR method. Further, we examined the changes in gene expression for all the isoforms in the CNS after conditioned taste aversion (CTA learning or backward conditioning as a control. The results showed that CTA learning increased LymCREB1 gene expression, but it did not change the activator/repressor ratio. Our findings showed that the repressor isoforms, as well as the activator ones, are expressed in large amounts in the CNS, and the gene expression of CREB1 isoforms appeared to be specific for the given stimulus. This was the first quantitative analysis of the expression patterns of CREB1 isoforms at the mRNA level and their association with learning behavior.

  5. Direction des Publications

    African Journals Online (AJOL)

    Synthese

    mélange pulvérulent de coke et de calcaire. La réduction est assurée par le gaz CO à 1250°C [2]. Le procédé Kawazaki iron powder utilise la calamine comme matière première et aussi CO comme gaz réducteur pour élaborer des poudres de fer. [3]. Un autre procédé plus connu qui fabrique les poudres de fer à partir de la.

  6. Glossaire des sigles

    OpenAIRE

    2015-01-01

    ABM Anti-ballistic missile = Missile antimissile balistique AGM Air-to-ground missile = Missile air-sol AIEA Agence Internationale de l’Energie Atomique ALCM Air-launched cruise missile = Missile de croisière air-sol ANSEA Association des Nations du Sud-Est asiatique ANT* Arme nucléaire tactique ASAT Anti-satellite = Arme antisatellite ASW Anti-submarine warfare = Guerre anti-sous-marine AWACS Airborne warning and control system = Système aérien de contrôle et d’alerte BMD Ballistic missile d...

  7. Progesterone receptor isoform A may regulate the effects of neoadjuvant aglepristone in canine mammary carcinoma

    DEFF Research Database (Denmark)

    Guil-Luna, Silvia; Stenvang, Jan; Brünner, Nils

    2014-01-01

    RNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20 mg/Kg of aglepristone (n¿=¿22) or vehicle (n¿=¿5) twice before surgery.ResultsFormalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor......-receptor positive and isoform-A positive tumours in aglepristone-treated dogs.ConclusionsThese findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A....

  8. Isolement et identification des levures.

    Directory of Open Access Journals (Sweden)

    S. DOMERCQ

    1967-06-01

    Full Text Available La fermentation du moût de raisin est assurée par les levures qui se trouvent sur la pellicule du raisin, sur les rafles, et aussi, par celles qui envahissent le matériel de vendange et de vinification dès que la récolte est commencée. L'apparition deLa fermentation du moût de raisin est assurée par les levures qui se trouvent sur la pellicule du raisin, sur les rafles, et aussi, par celles qui envahissent le matériel de vendange et de vinification dès que la récolte est commencée. L'apparition des signes de la fermentation est spontanée. La fermentation est rapide dans la majorité des cas, si elle devient trop violente et que la température s'élève dangeureusement, il faut la « canaliser », la calmer. Des accidents peuvent se produire; des arrêts de fermentation laissant des sucres non fermentés pouvant être attaqués par d'autres microorganismes, des développements de levures formant des substances nuisibles à la qualité; par la suite, il s'agit d'obtenir la stabilité du vin, en particulier, éviter les refermentations des vins doux. L'étude de ces problèmes nécessite une étude préliminaire, celle des levures responsables de la fermentation alcoolique du jus de raisin, qui ne peut être faite que sur des cultures pures, isolées au préalable à l'aide de prélèvements soigneusement réalisés.s signes de la fermentation est spontanée. La fermentation est rapide dans la majorité des cas, si elle devient trop violente et que la température s'élève dangeureusement, il faut la « canaliser », la calmer. Des accidents peuvent se produire; des arrêts de fermentation laissant des sucres non fermentés pouvant être attaqués par d'autres microorganismes, des développements de levures formant des substances nuisibles à la qualité; par la suite, il s'agit d'obtenir la stabilité du vin, en particulier, éviter les refermentations des vins doux. L'étude de ces problèmes nécessite une étude pr

  9. Le Débat des semences

    International Development Research Centre (IDRC) Digital Library (Canada)

    Solutions pour les lois nationales régissant le contrôle des ressources génétiques et des ...... des pouvoirs) qui reconnaissent, dans une certaine mesure, les droits de gestion collectifs des ...... documentés, les performances physiques, etc.

  10. Mécanique des sols et des roches

    CERN Document Server

    Vullier, Laurent; Zhao, Jian

    2016-01-01

    La mécanique des sols et la mécanique des roches sont des disciplines généralement traitées séparément dans la littérature. Pour la première fois, un traité réunit ces deux spécialités, en intégrant également les connaissances en lien avec les écoulements souterrains et les transferts thermiques. A la fois théorique et pratique, cet ouvrage propose tout d'abord une description détaillée de la nature et de la composition des sols et des roches, puis s'attache à la modélisation de problèmes aux conditions limites et présente les essais permettant de caractériser les sols et les roches, tant d'un point de vue mécanique qu'hydraulique et thermique. La problématique des sols non saturés et des écoulements multiphasiques est également abordée. Une attention particulière est portée aux lois de comportement mécanique et à la détermination de leurs paramètres par des essais in situ et en laboratoire, et l'ouvrage offre également une présentation détaillée des systèmes de classi...

  11. Organisation de l'activité neuronale cérébelleuse lors de d'une tâche de préhension et reste dans des rats déplaçant librement

    OpenAIRE

    Gao , Hongying

    2012-01-01

    The cerebellum is a brain structure involved in coordination complex motor actions such as voluntary movements. To achieve this function, the precise temporal control of a large population of neurons is required. While a large number of patterned population activity has been characterized in many major brain structures (thalamo-cortical system, basal ganglia, hippocampal formation, etc...), very little is currently known in the cerebellum. Therefore, I investigated the presence and characteri...

  12. Arogenate Dehydratase Isoforms Differentially Regulate Anthocyanin Biosynthesis in Arabidopsis thaliana.

    Science.gov (United States)

    Chen, Qingbo; Man, Cong; Li, Danning; Tan, Huijuan; Xie, Ye; Huang, Jirong

    2016-12-05

    Anthocyanins, a group of L-phenylalanine (Phe)-derived flavonoids, have been demonstrated to play important roles in plant stress resistance and interactions between plants and insects. Although the anthocyanin biosynthetic pathway and its regulatory mechanisms have been extensively studied, it remains unclear whether the level of Phe supply affects anthocyanin biosynthesis. Here, we investigated the roles of arogenate dehydratases (ADTs), the key enzymes that catalyze the conversion of arogenate into Phe, in sucrose-induced anthocyanin biosynthesis in Arabidopsis. Genetic analysis showed that all six ADT isoforms function redundantly in anthocyanin biosynthesis but have differential contributions. ADT2 contributes the most to anthocyanin accumulation, followed by ADT1 and ADT3, and ADT4-ADT6. We found that anthocyanin content is positively correlated with the levels of Phe and sucrose-induced ADT transcripts in seedlings. Consistently, addition of Phe to the medium could dramatically increase anthocyanin content in the wild-type plants and rescue the phenotype of the adt1 adt3 double mutant regarding the anthocyanin accumulation. Moreover, transgenic plants overexpressing ADT4, which appears to be less sensitive to Phe than overexpression of ADT2, hyperaccumulate Phe and produce elevated level of anthocyanins. Taken together, our results suggest that the level of Phe is an important regulatory factor for sustaining anthocyanin biosynthesis. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  13. Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus.

    Science.gov (United States)

    Arapovic, Jurica; Lenac, Tihana; Antulov, Ronald; Polic, Bojan; Ruzsics, Zsolt; Carayannopoulos, Leonidas N; Koszinowski, Ulrich H; Krmpotic, Astrid; Jonjic, Stipan

    2009-08-01

    The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. We show here that one of five RAE-1 isoforms, RAE-1delta, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1delta and RAE-1gamma in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1delta form which remains expressed on the surfaces of infected cells. This differential susceptibility to downregulation by MCMV is not a consequence of faster maturation of RAE-1delta compared to RAE-1gamma but rather an intrinsic property of the mature surface-resident protein. This difference can be attributed to the absence of a PLWY motif from RAE-1delta. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.

  14. Chirurgie des grassmanniennes

    CERN Document Server

    Lafforgue, Laurent

    2003-01-01

    Les compactifications diverses de variétés de modules sont un thème important et récurrent des mathématiques modernes, et elles connaissent un grand nombre d'applications. Ce livre traite le cas de cellules de Schubert minces, qui sont de sous-variétés naturelles de grassmanniennes. L'auteur a été amené à traiter ces questions par un cas particulier lié à ses travaux sur le programme de Langlands. Dans cette monographie, il en développe une théorie plus systématique, présentant le fortes similarités avec celle des modules du courbes stables. The various compactifications of moduli spaces are an important recurrent theme of modern mathematics, and they have a large number of applications. This book treats the case of thin Schubert varieties, which are natural subvarieties of Grassmannians. The author was led to these questions by a particular case linked to his work on the Langlands program. In this monograph, he develops the theory in a more systematic way, which exhibits strong similarities...

  15. Comportement des polluants des eaux pluviales urbaines en ...

    African Journals Online (AJOL)

    développement et la croissance des organismes vivant dans l'eau et particulièrement les micro- organismes. Le suivi des températures enregistrées oscille entre 9 et 16°C dans les trois sites d'observation durant la période ... de la lumière du soleil. Le site C est bien aéré et .... Effets de différents modes de gestion des eaux ...

  16. Approche historique des classifications en psychiatrie

    OpenAIRE

    Garrabé , J.

    2011-01-01

    Resume Des le milieu du xixe siecle s?est posee la question des criteres de classification des maladies. Pour les maladies mentales, diverses classifications ont alors ete proposees par des auteurs francais (Morel) et allemands (Kahlbaum, Kraepelin). A partir de la fin du xixe siecle, le Bureau International de Statistique (Paris) a publie a une Classification Internationale des Maladies, a revision decennale (J. Bertillon). Cette tache a ete poursuivie dans l?entre-deux-guerres pa...

  17. Complications du traitement traditionnel des fractures : aspects ...

    African Journals Online (AJOL)

    Tous les patients reçus avec des complications du traitement traditionnel des fractures ont été inclus dans ce travail. Le diagnostic des lésions était clinique et radiologique. Nous avions reçu 51 patients porteurs de complications suite à des traitements de médecine traditionnelle, soit 13,7% du total des patients hospitalisés ...

  18. Receptor-isoform-selective insulin analogues give tissue-preferential effects

    DEFF Research Database (Denmark)

    Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi

    2011-01-01

    The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can...... be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI...... (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI...

  19. The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease

    Directory of Open Access Journals (Sweden)

    Michael V. Clausen

    2017-06-01

    Full Text Available The sodium and potassium gradients across the plasma membrane are used by animal cells for numerous processes, and the range of demands requires that the responsible ion pump, the Na,K-ATPase, can be fine-tuned to the different cellular needs. Therefore, several isoforms are expressed of each of the three subunits that make a Na,K-ATPase, the alpha, beta and FXYD subunits. This review summarizes the various roles and expression patterns of the Na,K-ATPase subunit isoforms and maps the sequence variations to compare the differences structurally. Mutations in the Na,K-ATPase genes encoding alpha subunit isoforms have severe physiological consequences, causing very distinct, often neurological diseases. The differences in the pathophysiological effects of mutations further underline how the kinetic parameters, regulation and proteomic interactions of the Na,K-ATPase isoforms are optimized for the individual cellular needs.

  20. The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease.

    Science.gov (United States)

    Clausen, Michael V; Hilbers, Florian; Poulsen, Hanne

    2017-01-01

    The sodium and potassium gradients across the plasma membrane are used by animal cells for numerous processes, and the range of demands requires that the responsible ion pump, the Na,K-ATPase, can be fine-tuned to the different cellular needs. Therefore, several isoforms are expressed of each of the three subunits that make a Na,K-ATPase, the alpha, beta and FXYD subunits. This review summarizes the various roles and expression patterns of the Na,K-ATPase subunit isoforms and maps the sequence variations to compare the differences structurally. Mutations in the Na,K-ATPase genes encoding alpha subunit isoforms have severe physiological consequences, causing very distinct, often neurological diseases. The differences in the pathophysiological effects of mutations further underline how the kinetic parameters, regulation and proteomic interactions of the Na,K-ATPase isoforms are optimized for the individual cellular needs.

  1. An abnormally glycosylated isoform of erythropoietin in hemangioblastoma is associated with polycythemia.

    Science.gov (United States)

    Delanghe, Sigurd E; Dierick, Jan; Maenhout, Thomas M; Zabeau, Lennart; Tavernier, Jan; Claes, Kathleen; Bleyen, Joris; Delanghe, Joris R

    2015-01-01

    Hemangioblastomas express erythropoietin and the patients often present with polycythemia. Serum erythropoietin was measured using a commercial immunoassay, a functional erythropoietin assay and iso-electric focusing. Despite the polycythemia, serum erythropoietin remained low, while a functional erythropoietin-assay showed a 4-5 higher activity in serum compared to the immunoassay. Iso-electric focusing of serum erythropoietin indicated overrepresentation of highly sialylated erythropoietin isoforms produced by the tumor. As a result, altered affinity of the monoclonal antibody used in the immunoassay for the hypersialylated isoforms was suggested. Analysis of erythropoietin isoforms may be helpful in distinguishing the ectopic erythropoietin isoforms from normally glycosylated erythropoietin. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Altered β-Amyloid Precursor Protein Isoforms in Mexican Alzheimer’s Disease Patients

    Directory of Open Access Journals (Sweden)

    V. J. Sánchez-González

    2006-01-01

    Full Text Available Objective: To determine the β-amyloid precursor protein (βAPP isoforms ratio as a risk factor for Alzheimer’s Disease and to assess its relationship with demographic and genetic variables of the disease.

  3. Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

    Science.gov (United States)

    Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

    1999-01-01

    Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

  4. Development of isoform-specific sensors of polypeptide GalNAc-transferase activity

    DEFF Research Database (Denmark)

    Song, Lina; Bachert, Collin; Schjoldager, Katrine T

    2014-01-01

    sequence influenced their activity and required modification, which we carried out based on previous in vitro work. Significantly, the modified T2 and T3 sensors were activated only in cells lacking their corresponding isozymes. Thus, we have developed T2- and T3-specific sensors that will be valuable......Humans express up to 20 isoforms of GalNAc-transferase (herein T1-T20) that localize to the Golgi apparatus and initiate O-glycosylation. Regulation of this enzyme family affects a vast array of proteins transiting the secretory pathway and diseases arise upon misregulation of specific isoforms....... Surprisingly, molecular probes to monitor GalNAc-transferase activity are lacking and there exist no effective global or isoform-specific inhibitors. Here we describe the development of T2- and T3-isoform specific fluorescence sensors that traffic in the secretory pathway. Each sensor yielded little signal...

  5. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    Full Text Available We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2 in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2 and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2 generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. The streptozotocin (STZ murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold. Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively.The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal

  6. An application of neural network in geophysical prospecting. Electrical resistivity at Las Virgenes geothermal field, Baja California Sur, Mexico; Una aplicacion de las redes neuronales a la prospeccion geofisica. Resistividad electrica en las Tres Virgenes, Baja California Sur, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Palma Guzman, Sergio Hugo [Comision Federal de Electricidad, Morelia, Michoacan (Mexico)

    2000-12-01

    The technology of the neural network is presented with geophysical focus in the Las Virgenes geothermal field, Baja California Sur, Mexico. The results obtained when extrapolating the associative data of the prospecting magnetoteluria and Vertical Electric Sounding, on the area of the geothermal wells to the rest of the area, allows to classify zones of interest for the geothermal exploitation. Also, the use of these associative parameters with the information of the stabilized temperature of the wells, they allow to predict temperatures for the rest of the area. [Spanish] Se presenta una aplicacion de la tecnologia de las redes neuronales con enfoque geofisico en el campo geotermico de Las Virgenes, Baja California Sur, Mexico. Los resultados obtenidos al extrapolar los datos asociativos de las prospecciones geoelectricas de magnetoteluria y sondeos electricos verticales, en la zona de los pozos geotermicos al resto del area, permiten clasificar zonas de interes para la explotacion geotermica. Tambien, la utilizacion de estos parametros asociativos con la informacion de la temperatura estabilizada de los pozos, permiten predecir temperaturas para la misma area.

  7. Prediction of the daily share price fluctuations of SURAMINV. A neural netword model Predicción del comportamiento diario de la acción de SURAMINV. Un modelo de redes neuronales

    Directory of Open Access Journals (Sweden)

    Jaime Enrique Arrieta Bechara

    2009-12-01

    Full Text Available As opposed to the weak form of efficient-market hypothesis, the current study shows that it is possible to do good predictions about the daily share price fluctuations of Suraminv, using artificial neural network models. Furthermore, the forecasts obtained are used to analyze the possibility of gaining extraordinary returns with regard to the Buy & Hold strategy, through negotiation systems with basic rules.La investigación muestra que es posible realizar, por medio de modelos de redes neuronales artificiales, buenas predicciones sobre el comportamiento diario de la acción de SURAMINV. Tales resultados contrarían la hipótesis de la teoría de eficiencia débil de mercado. A partir de dichas predicciones y con el uso de sistemas de negociación, se evalúa la posibilidad de obtener rendimientos extraordinarios sobre la estrategia Buy & Hold teniendo en cuenta costos de transacción y oportunidad.

  8. Diseño de redes neuronales con aprendizaje combinado de retropropagación y búsqueda aleatoria progresiva aplicado a la determinación de austenita retenida en aceros TRIP

    Directory of Open Access Journals (Sweden)

    Capdevila, C.

    2010-12-01

    Full Text Available At the beginning of the decade of the nineties, the industrial interest for TRIP steels leads to a significant increase of the investigation and application in this field. In this work, the flexibility of neural networks for the modelling of complex properties is used to tackle the problem of determining the retained austenite content in TRIP-steel. Applying a combination of two learning algorithms (backpropagation and creeping-random-search for the neural network, a model has been created that enables the prediction of retained austenite in low-Si / low-Al multiphase steels as a function of processing parameters.

    A partir de los años noventa, el interés que los aceros TRIP despiertan en la industria ha producido un incremento considerable de su estudio y aplicación. En este trabajo, aprovechando la flexibilidad que las redes neuronales proporcionan para la modelización de propiedades complejas, se ha abordado el problema de la determinación de la austenita retenida en los aceros TRIP. Una combinación de dos algoritmos de aprendizaje (retropropagación y búsqueda aleatoria progresiva de la red neuronal ha permitido crear un modelo que predice la cantidad de austenita retenida en aceros multifase con bajo contenido en aluminio y silicio en función de los parámetros de procesado.

  9. Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia.

    Science.gov (United States)

    Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna; Borrelli, Emiliana

    2013-06-01

    Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R-/- mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.

  10. Network-Based Isoform Quantification with RNA-Seq Data for Cancer Transcriptome Analysis.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-12-01

    Full Text Available High-throughput mRNA sequencing (RNA-Seq is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-Seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abundances of the neighboring isoforms by domain-domain interactions in the network are positively correlated, Net-RSTQ models the expression of the neighboring transcripts as Dirichlet priors on the likelihood of the observed read alignments against the transcripts in one gene. The transcript abundances of all the genes are then jointly estimated with alternating optimization of multiple EM problems. In simulation Net-RSTQ effectively improved isoform transcript quantifications when isoform co-expressions correlate with their interactions. qRT-PCR results on 25 multi-isoform genes in a stem cell line, an ovarian cancer cell line, and a breast cancer cell line also showed that Net-RSTQ estimated more consistent isoform proportions with RNA-Seq data. In the experiments on the RNA-Seq data in The Cancer Genome Atlas (TCGA, the transcript abundances estimated by Net-RSTQ are more informative for patient sample classification of ovarian cancer, breast cancer and lung cancer. All experimental results collectively support that Net-RSTQ is a promising approach for isoform quantification. Net-RSTQ toolbox is available at http://compbio.cs.umn.edu/Net-RSTQ/.

  11. Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene

    Directory of Open Access Journals (Sweden)

    Mattei Marie-Geneviève

    2004-07-01

    Full Text Available Abstract Background The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis. Results The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-α and -γ and two other long isoforms (Spatial-δ and -ε comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-β, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-β protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved. Conclusions The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-α, -β and -γ highly expressed in the thymus and two long isoforms (Spatial-δ and -ε highly expressed in the testis. These alternative spliced variants could have a tissue specific function.

  12. Electrophoretic Mobility of Cardiac Myosin Heavy Chain Isoforms Revisited: Application of MALDI TOF/TOF Analysis

    Czech Academy of Sciences Publication Activity Database

    Arnoštová, P.; Jedelsky, P. L.; Soukup, Tomáš; Žurmanová, J.

    2011-01-01

    Roč. 2011, - (2011), e634253 ISSN 1110-7243 R&D Projects: GA AV ČR IAAX01110901; GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac MyHC isoforms * MyHC isoform mobility * effect of thyroid hormones * mass spectrometry * SDS-PAGE and western blot Subject RIV: ED - Physiology Impact factor: 2.436, year: 2011

  13. Kinetics of local and systemic isoforms of serum amyloid A in bovine mastitic milk

    DEFF Research Database (Denmark)

    Jacobsen, Stine; Niewold, T.A.; Kornalijnslijper, E.

    2005-01-01

    The aim of the present study was to characterise the serum amyloid A (SAA) response to intramammary inoculation of Escherichia coli and to examine the distribution of hepatically and extrahepatically pruduced SAA isoforms in plasma and milk fra cows with mastitis.......The aim of the present study was to characterise the serum amyloid A (SAA) response to intramammary inoculation of Escherichia coli and to examine the distribution of hepatically and extrahepatically pruduced SAA isoforms in plasma and milk fra cows with mastitis....

  14. Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization.

    Science.gov (United States)

    Magnusson, P; Farley, J R

    2002-12-01

    High-performance liquid chromatography (HPLC) separates three human bone alkaline phosphatase (BALP) isoforms in serum; two major BALP isoforms, B1 and B2, and a minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal ALP. The current studies were intended to identify an in vitro source of the BALP isoforms for physical, biochemical, and immunological characterizations. The three BALP isoforms were identified in extracts of human osteosarcoma (SaOS-2) cells, by HPLC, after separation by anion-exchange chromatography. All three BALP isoforms were similar with respect to freeze-thaw stability, solubility, heat inactivation, and inhibition by L-phenylalanine, L-homoarginine, and levamisole. The isoforms were also kinetically similar (i.e., maximal velocity and KM at pH 8.8 and pH 10.0). The isoforms differed, however, with respect to sensitivity to precipitation with wheat germ agglutinin (WGA), P acid residues was estimated to be 29 and 45, for each B1 and B2 homodimer, respectively. Apparent discrepancies between these estimates of molecular weight and estimates based on gel filtration chromatography were attributed to nonspecific interactions between carbohydrate residues and the gel filtration beads. All three BALP isoforms showed similar dose-dependent linearity in the commercial Alkphase-B and Tandem-MP Ostase immunoassays, r = 0.944 and r = 0.985, respectively (P acid residues compared with B/I, which mainly explains the apparent differences in molecular weight. Future investigations will focus on the clinical and functional significance of the revealed differences in sialic acid residues.

  15. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Directory of Open Access Journals (Sweden)

    Niels Jacob Aachmann-Andersen

    Full Text Available The membrane-assisted isoform immunoassay (MAIIA quantitates erythropoietin (EPO isoforms as percentages of migrated isoforms (PMI. We evaluated the effect of recombinant human EPO (rhEPO on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13; high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13; or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3 % (mean (SD. High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2% (p<0.00001 and 45.2 (7.3% (p<0.00001. Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8% (p<0.00001 and 46.1 (10.4% (p<0.00001. In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4% (p=0.029; low-dose Epoetin beta: 73.1 (17.8% (p=0.039. In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  16. Differential expression of mRNAs for protein kinase inhibitor isoforms in mouse brain.

    OpenAIRE

    Seasholtz, A F; Gamm, D M; Ballestero, R P; Scarpetta, M A; Uhler, M D

    1995-01-01

    Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependent protein kinase (PKA) and phosphorylation of neuronal substrate proteins, including transcription factors and ion channels. Here, we have characterized the gene expression of two isoforms of a protein kinase inhibitor (PKI) specific for PKA in mouse brain by RNase protection and in situ hybridization histochemistry. The studies demonstrate that the PKI alpha isoform is abundant in many ...

  17. Myosin heavy-chain isoforms in the flight and leg muscles of hummingbirds and zebra finches.

    Science.gov (United States)

    Velten, Brandy P; Welch, Kenneth C

    2014-06-01

    Myosin heavy chain (MHC) isoform complement is intimately related to a muscle's contractile properties, yet relatively little is known about avian MHC isoforms or how they may vary with fiber type and/or the contractile properties of a muscle. The rapid shortening of muscles necessary to power flight at the high wingbeat frequencies of ruby-throated hummingbirds and zebra finches (25-60 Hz), along with the varied morphology and use of the hummingbird hindlimb, provides a unique opportunity to understand how contractile and morphological properties of avian muscle may be reflected in MHC expression. Isoforms of the hummingbird and zebra finch flight and hindlimb muscles were electrophoretically separated and compared with those of other avian species representing different contractile properties and fiber types. The flight muscles of the study species operate at drastically different contraction rates and are composed of different histochemically defined fiber types, yet each exhibited the same, single MHC isoform corresponding to the chicken adult fast isoform. Thus, despite quantitative differences in the contractile demands of flight muscles across species, this isoform appears necessary for meeting the performance demands of avian powered flight. Variation in flight muscle contractile performance across species may be due to differences in the structural composition of this conserved isoform and/or variation within other mechanically linked proteins. The leg muscles were more varied in their MHC isoform composition across both muscles and species. The disparity in hindlimb MHC expression between hummingbirds and the other species highlights previously observed differences in fiber type composition and thrust production during take-off. Copyright © 2014 the American Physiological Society.

  18. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

    Directory of Open Access Journals (Sweden)

    Thomas P Stricker

    2017-03-01

    Full Text Available Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+ subtype and fourteen triple negative (TN subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  19. Des cartes dans la classe…

    Directory of Open Access Journals (Sweden)

    R. Gimeno

    1990-09-01

    Full Text Available La majorité des enseignants qui veulent faire des cartes — et les faire réaliser aux élèves — pour répondre aux exigences des instructions officielles, doivent surmonter leur manque de compétences en cartographie et en didactique ainsi que les difficultés propres aux logiciels de cartographie encore peu performants. Ces compétences et la réflexion qui les accompagne sont pourtant accessibles aux enfants de l’école élémentaire…

  20. Diversification des moyens de subsistance des petits producteurs de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention permettra à l'Institut international de recherche sur les cultures des zones tropicales ... In ROSSA's latest bulletin issue: A farewell message from Simon Carter, the Regional Director of the ... Cigarette Taxation in Tanzania.

  1. L'exode des cerveaux et le renforcement des capacités en Afrique ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 févr. 2011 ... Ce phénomène ébranle les assises économiques et politiques de bien des pays africains. ... le défi consiste à recruter ces cerveaux. ... des missions africaines, des organisations non gouvernementales et des groupes de la diaspora réunis pour parler de l'exode des cerveaux en Afrique et des stratégies à ...

  2. Evaluation des pratiques de gestion des adventices en riziculture ...

    African Journals Online (AJOL)

    Le riz est l'aliment principal pour la quasi-totalité des populations vivant en Côte d'Ivoire. Cependant, les adventices sont considérées comme la contrainte biologique la plus importante faisant obstacle à la production rizicole. L'objectif de cette étude menée en 2015 était d'évaluer différentes techniques de gestion des ...

  3. Cartographie des zones d'intervention des partenaires techniques et ...

    African Journals Online (AJOL)

    cartographier les zones d'intervention des partenaires techniques et financiers au Bénin. L'approche méthodologique utilisée a consisté à la recherche documentaire, à la collecte de données auprès des partenaires techniques et financiers et à l'analyse de ces données. Les résultats ont permis de constater que cent dix ...

  4. Modernisation des marchés agroalimentaires - inclusion des petits ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les marchés agroalimentaires connaissent de rapides changements dans les pays en développement et les pays en transition. Sous l'influence de la libéralisation du commerce et des nouvelles technologies de transformation des aliments et de commerce de détail, les marchés agroalimentaires évoluent vers une plus ...

  5. C/EBPβ Isoforms Expression in the Rat Brain during the Estrous Cycle

    Directory of Open Access Journals (Sweden)

    Valeria Hansberg-Pastor

    2015-01-01

    Full Text Available The CCAAT/enhancer-binding protein beta (C/EBPβ is a transcription factor expressed in different areas of the brain that regulates the expression of several genes involved in cell differentiation and proliferation. This protein has three isoforms (LAP1, LAP2, and LIP with different transcription activation potential. The role of female sex hormones in the expression pattern of C/EBPβ isoforms in the rat brain has not yet been described. In this study we demonstrate by western blot that the expression of the three C/EBPβ isoforms changes in different brain areas during the estrous cycle. In the cerebellum, LAP2 content diminished on diestrus and proestrus and LIP content diminished on proestrus and estrus days. In the prefrontal cortex, LIP content was higher on proestrus and estrus days. In the hippocampus, LAP isoforms presented a switch on diestrus day, since LAP1 content was the highest while that of LAP2 was the lowest. The LAP2 isoform was the most abundant one in all the three brain areas. The LAP/LIP ratio changed throughout the cycle and was tissue specific. These results suggest that C/EBPβ isoforms expression changes in a tissue-specific manner in the rat brain due to the changes in sex steroid hormone levels presented during the estrous cycle.

  6. Proliferation marker pKi-67 occurs in different isoforms with various cellular effects.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Finniss, Susan; Bögler, Oliver; Duchrow, Michael

    2004-04-15

    The Ki-67 antigen, pKi-67, is a commonly used proliferation marker in research and pathology. It has been recognized that the protein exists in two different splice variants that differ in one exon. In the current work, we present three new splice variants of human pKi-67 consisting of two naturally occurring isoforms and one atypical version. Additionally, data is presented indicating that alternative splicing of the pKi-67 N-terminus is common in tumor cell lines. Analyzing 93 tissues mainly consisting of brain tumor specimens, we found evidence that long and short isoform can be expressed independently of each other. Induction of mitosis in human peripheral blood mononuclear cells revealed that short pKi-67 appears earlier in the cell cycle than the long isoform and reaches its expression maximum when transcription of the latter sets in. Finally, transfection of mammalian culture cells with exon 7 (specific for the long pKi-67 isoform and not present in the short isoform) in a tetracycline regulated expression system decreased the rate of cell proliferation without affecting the cell cycle. In summary, we present evidence that the pKi-67 N-terminus is differentially spliced resulting in at least five different isoforms with different functions. Copyright 2004 Wiley-Liss, Inc.

  7. Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

    Science.gov (United States)

    Maheshwari, Akhil; Voitenok, Nikolai N; Akalovich, Svetlana; Shaik, Sadiq S; Randolph, David A; Sims, Brian; Patel, Rakesh P; Killingsworth, Cheryl R; Fallon, Michael B; Ohls, Robin K

    2009-04-01

    Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

  8. Characterization of 14-3-3 isoforms expressed in the Echinococcus granulosus pathogenic larval stage.

    Science.gov (United States)

    Teichmann, Aline; Vargas, Daiani M; Monteiro, Karina M; Meneghetti, Bruna V; Dutra, Cristine S; Paredes, Rodolfo; Galanti, Norbel; Zaha, Arnaldo; Ferreira, Henrique B

    2015-04-03

    The 14-3-3 protein family of eukaryotic regulators was studied in Echinococcus granulosus, the causative agent of cystic hydatid disease. These proteins mediate important cellular processes in eukaryotes and are expected to play important roles in parasite biology. Six isoforms of E. granulosus 14-3-3 genes and proteins (Eg14-3-3.1-6) were analyzed, and their phylogenetic relationships were established with bona fide 14-3-3 orthologous proteins from eukaryotic species. Eg14-3-3 isoforms with previous evidence of expression (Eg14-3-3.1-4) in E. granulosus pathogenic larval stage (metacestode) were cloned, and recombinant proteins were used for functional studies. These protein isoforms were detected in different components of E. granulosus metacestode, including interface components with the host. The roles that are played by Eg14-3-3 proteins in parasite biology were inferred from the repertoires of interacting proteins with each isoform, as assessed by gel overlay, cross-linking, and affinity chromatography assays. A total of 95 Eg14-3-3 protein ligands were identified by mass spectrometry. Eg14-3-3 isoforms have shared partners (44 proteins), indicating some overlapping functions; however, they also bind exclusive partners (51 proteins), suggesting Eg14-3-3 functional specialization. These ligand repertoires indicate the involvement of Eg14-3-3 proteins in multiple biochemical pathways in the E. granulosus metacestode and note some degree of isoform specialization.

  9. Molecular modeling study on tunnel behavior in different histone deacetylase isoforms.

    Directory of Open Access Journals (Sweden)

    Sundarapandian Thangapandian

    Full Text Available Histone deacetylases (HDACs have emerged as effective therapeutic targets in the treatment of various diseases including cancers as these enzymes directly involved in the epigenetic regulation of genes. However the development of isoform-selective HDAC inhibitors has been a challenge till date since all HDAC enzymes possess conserved tunnel-like active site. In this study, using molecular dynamics simulation we have analyzed the behavior of tunnels present in HDAC8, 10, and 11 enzymes of class I, II, and IV, respectively. We have identified the equivalent tunnel forming amino acids in these three isoforms and found that they are very much conserved with subtle differences to be utilized in selective inhibitor development. One amino acid, methionine of HDAC8, among six tunnel forming residues is different in isoforms of other classes (glutamic acid (E in HDAC10 and leucine (L in HDAC 11 based on which mutations were introduced in HDAC11, the less studied HDAC isoform, to observe the effects of this change. The HDAC8-like (L268M mutation in the tunnel forming residues has almost maintained the deep and narrow tunnel as present in HDAC8 whereas HDAC10-like (L268E mutation has changed the tunnel wider and shallow as observed in HDAC10. These results explained the importance of the single change in the tunnel formation in different isoforms. The observations from this study can be utilized in the development of isoform-selective HDAC inhibitors.

  10. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    Science.gov (United States)

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

  11. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution

    DEFF Research Database (Denmark)

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross......-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N......-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI...

  12. Die Versprachlichung des Sakralen

    DEFF Research Database (Denmark)

    Larsen, Øjvind

    2011-01-01

    transformation of the sacred as a harmonious theory of secularization. However, if we follow Weber in his religious-sociological considerations of modernity, we reach a tragic theory of secularization that poses the real problem that modernity’s connection to the sacred has been dissolved.......Habermas claims in connection with his development of the theory of communicative action that the sacred is transformed in a positive way and can take the form of free deliberation in society, the so-called Versprachlichung des Sakralen. The thesis is that the authority which could be found...... in religion and which is of fundamental significance for the integration of pre-modern societies is taken over by modern societies in forms of deliberation. Habermas develops his thesis in a discussion of Durkheim’s religious-sociological considerations. Habermas presents his thesis about the linguistic...

  13. Code des baux 2018

    CERN Document Server

    Vial-Pedroletti, Béatrice; Kendérian, Fabien; Chavance, Emmanuelle; Coutan-Lapalus, Christelle

    2017-01-01

    Le code des baux 2018 vous offre un contenu extrêmement pratique, fiable et à jour au 1er août 2017. Cette 16e édition intègre notamment : le décret du 27 juillet 2017 relatif à l’évolution de certains loyers dans le cadre d’une nouvelle location ou d’un renouvellement de bail, pris en application de l’article 18 de la loi n° 89-462 du 6 juillet 1989 ; la loi du 27 janvier 2017 relative à l’égalité et à la citoyenneté ; la loi du 9 décembre 2016 relative à la transparence, à la lutte contre la corruption et à la modernisation de la vie économique ; la loi du 18 novembre 2016 de modernisation de la justice du xxie siècle

  14. Digitalisierung des Kulturellen Erbes (Europas)

    NARCIS (Netherlands)

    Gruber, Marion

    2011-01-01

    Gruber, M. R. (2011, 13 December). Digitalisierung des Kulturellen Erbes (Europas). Guest lecture at the IPMZ - Institute of Mass Communication and Media Research, Devision Media Change & Innovation, University of Zurich, Switzerland.

  15. Vecteurs Singuliers des Theories des Champs Conformes Minimales

    Science.gov (United States)

    Benoit, Louis

    En 1984 Belavin, Polyakov et Zamolodchikov revolutionnent la theorie des champs en explicitant une nouvelle gamme de theories, les theories quantiques des champs bidimensionnelles invariantes sous les transformations conformes. L'algebre des transformations conformes de l'espace-temps presente une caracteristique remarquable: en deux dimensions elle possede un nombre infini de generateurs. Cette propriete impose de telles conditions aux fonctions de correlations qu'il est possible de les evaluer sans aucune approximation. Les champs des theories conformes appartiennent a des representations de plus haut poids de l'algebre de Virasoro, une extension centrale de l'algebre conforme du plan. Ces representations sont etiquetees par h, le poids conforme de leur vecteur de plus haut poids, et par la charge centrale c, le facteur de l'extension centrale, commune a toutes les representations d'une meme theorie. Les theories conformes minimales sont constituees d'un nombre fini de representations. Parmi celles-ci se trouvent des theories unitaires dont les representation forment la serie discrete de l'algebre de Virasoro; leur poids h a la forme h_{p,q}(m)=[ (p(m+1) -qm)^2-1] (4m(m+1)), ou p,q et m sont des entiers positifs et p+q= 2. Ces representations possedent un sous-espace invariant engendre par deux sous-representations avec h_1=h_{p,q} + pq et h_2=h_{p,q} + (m-p)(m+1-q) dont chacun des vecteurs de plus haut poids portent le nom de vecteur singulier et sont notes respectivement |Psi _{p,q}> et |Psi_{m-p,m+1-q}>. . Les theories super-conformes sont une version super-symetrique des theories conformes. Leurs champs appartiennent a des representation de plus haut poids de l'algebre de Neveu-Schwarz, une des deux extensions super -symetriques de l'algebre de Virasoro. Les theories super -conformes minimales possedent la meme structure que les theories conformes minimales. Les representations sont elements de la serie h_{p,q}= [ (p(m+2)-qm)^2-4] /(8m(m+2)) ou p,q et m sont

  16. P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells

    International Nuclear Information System (INIS)

    Liu Yang; Dong Qianze; Zhao Yue; Dong Xinjun; Miao Yuan; Dai Shundong; Yang Zhiqiang; Zhang Di; Wang Yan; Li Qingchang; Zhao Chen; Wang Enhua

    2009-01-01

    Different isoforms of p120-catenin (p120ctn), a member of the Armadillo gene family, are variably expressed in different tissues as a result of alternative splicing and the use of multiple translation initiation codons. When expressed in cancer cells, these isoforms may confer different properties with respect to cell adhesion and invasion. We have previously reported that the p120ctn isoforms 1 and 3 were the most highly expressed isoforms in normal lung tissues, and their expression level was reduced in lung tumor cells. To precisely define their biological roles, we transfected p120ctn isoforms 1A and 3A into the lung cancer cell lines A549 and NCI-H460. Enhanced expression of p120ctn isoform 1A not only upregulated E-cadherin and β-catenin, but also downregulated the Rac1 activity, and as a result, inhibited the ability of cells to invade. In contrast, overexpression of p120ctn isoform 3A led to the inactivation of Cdc42 and the activation of RhoA, and had a smaller influence on invasion. However, we found that isoform 3A had a greater ability than isoform 1A in both inhibiting the cell cycle and reducing tumor cell proliferation. The present study revealed that p120ctn isoforms 1A and 3A differently regulated the adhesive, proliferative, and invasive properties of lung cancer cells through distinct mechanisms

  17. Expression of 14-3-3 protein isoforms in mouse oocytes, eggs and ovarian follicular development

    Directory of Open Access Journals (Sweden)

    De Santanu

    2012-01-01

    Full Text Available Abstract Background The 14-3-3 (YWHA proteins are a highly conserved, ubiquitously expressed family of proteins. Seven mammalian isoforms of 14-3-3 are known (β, γ, ε, ζ, η, τ and, σ. These proteins associate with many intracellular proteins involved in a variety of cellular processes including regulation of the cell cycle, metabolism and protein trafficking. We are particularly interested in the role of 14-3-3 in meiosis in mammalian eggs and the role 14-3-3 proteins may play in ovarian function. Therefore, we examined the expression of 14-3-3 proteins in mouse oocyte and egg extracts by Western blotting after polyacrylamide gel electrophoresis, viewed fixed cells by indirect immunofluorescence, and examined mouse ovarian cells by immunohistochemical staining to study the expression of the different 14-3-3 isoforms. Results We have determined that all of the mammalian 14-3-3 isoforms are expressed in mouse eggs and ovarian follicular cells including oocytes. Immunofluorescence confocal microscopy of isolated oocytes and eggs confirmed the presence of all of the isoforms with characteristic differences in some of their intracellular localizations. For example, some isoforms (β, ε, γ, and ζ are expressed more prominently in peripheral cytoplasm compared to the germinal vesicles in oocytes, but are uniformly dispersed within eggs. On the other hand, 14-3-3η is diffusely dispersed in the oocyte, but attains a uniform punctate distribution in the egg with marked accumulation in the region of the meiotic spindle apparatus. Immunohistochemical staining detected all isoforms within ovarian follicles, with some similarities as well as notable differences in relative amounts, localizations and patterns of expression in multiple cell types at various stages of follicular development. Conclusions We found that mouse oocytes, eggs and follicular cells within the ovary express all seven isoforms of the 14-3-3 protein. Examination of the

  18. Differential CARM1 Isoform Expression in Subcellular Compartments and among Malignant and Benign Breast Tumors.

    Directory of Open Access Journals (Sweden)

    David Shlensky

    Full Text Available Coactivator-associated arginine methyltransferase 1 (CARM1 is a coactivator for ERα and cancer-relevant transcription factors, and can methylate diverse cellular targets including histones. CARM1 is expressed in one of two alternative splice isoforms, full-length CARM1 (CARM1FL and truncated CARM1 (CARM1ΔE15. CARM1FL and CARM1ΔE15 function differently in transcriptional regulation, protein methylation, and mediation of pre-mRNA splicing in cellular models.To investigate the functional roles and the prognosis potential of CARM1 alternative spliced isoforms in breast cancer, we used recently developed antibodies to detect differential CARM1 isoform expression in subcellular compartments and among malignant and benign breast tumors.Immunofluorescence in MDA-MB-231 and BG-1 cell lines demonstrated that CARM1ΔE15 is the dominant isoform expressed in the cytoplasm, and CARM1FL is more nuclear localized. CARM1ΔE15 was found to be more sensitive to Hsp90 inhibition than CARM1FL, indicating that the truncated isoform may be the oncogenic form. Clinical cancer samples did not have significantly higher expression of CARM1FL or CARM1ΔE15 than benign breast samples at the level of mRNA or histology. Furthermore neither CARM1FL nor CARM1ΔE15 expression correlated with breast cancer molecular subtypes, tumor size, or lymph node involvement.The analysis presented here lends new insights into the possible oncogenic role of CARM1ΔE15. This study also demonstrates no obvious association of CARM1 isoform expression and clinical correlates in breast cancer. Recent studies, however, have shown that CARM1 expression correlates with poor prognosis, indicating a need for further studies of both CARM1 isoforms in a large cohort of breast cancer specimens.

  19. Drosophila TRPA1 isoforms detect UV light via photochemical production of H2O2

    Science.gov (United States)

    Guntur, Ananya R.; Gu, Pengyu; Takle, Kendra; Chen, Jingyi; Xiang, Yang; Yang, Chung-Hui

    2015-01-01

    The transient receptor potential A1 (TRPA1) channel is an evolutionarily conserved detector of temperature and irritant chemicals. Here, we show that two specific isoforms of TRPA1 in Drosophila are H2O2 sensitive and that they can detect strong UV light via sensing light-induced production of H2O2. We found that ectopic expression of these H2O2-sensitive Drosophila TRPA1 (dTRPA1) isoforms conferred UV sensitivity to light-insensitive HEK293 cells and Drosophila neurons, whereas expressing the H2O2-insensitive isoform did not. Curiously, when expressed in one specific group of motor neurons in adult flies, the H2O2-sensitive dTRPA1 isoforms were as competent as the blue light-gated channelrhodopsin-2 in triggering motor output in response to light. We found that the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the adipokinetic hormone (AKH) in the larval ring gland endogenously express these H2O2-sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC cells required dTRPA1 and H2O2 production but not conventional phototransduction molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV light via photochemical production of H2O2. We speculate that UV sensitivity conferred by these isoforms in CC cells may allow young larvae to activate stress response—a function of CC cells—when they encounter strong UV, an aversive stimulus for young larvae. PMID:26443856

  20. Gene duplication and the evolution of hemoglobin isoform differentiation in birds.

    Science.gov (United States)

    Grispo, Michael T; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F

    2012-11-02

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α(A)-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α(D)-globin gene). The α(D)-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O(2) affinity in the presence of allosteric effectors such as organic phosphates and Cl(-) ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O(2) affinity stems primarily from changes in the O(2) association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the α(D)-globin gene that is shared with the embryonic α-like globin gene.

  1. Gene Duplication and the Evolution of Hemoglobin Isoform Differentiation in Birds*

    Science.gov (United States)

    Grispo, Michael T.; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.

    2012-01-01

    The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the αA-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the αD-globin gene). The αD-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O2 affinity in the presence of allosteric effectors such as organic phosphates and Cl− ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O2 affinity stems primarily from changes in the O2 association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the αD-globin gene that is shared with the embryonic α-like globin gene. PMID:22962007

  2. Development and characterization of human monoclonal antibodies that neutralize multiple TGFβ isoforms.

    Science.gov (United States)

    Bedinger, Daniel; Lao, Llewelyn; Khan, Shireen; Lee, Steve; Takeuchi, Toshihiko; Mirza, Amer M

    2016-01-01

    Transforming growth factor (TGF)β levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFβ1, 2, and 3. As multiple TGFβ isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFβ isoforms. Fully human antibody phage display libraries were used to discover a number of antibodies that bind and neutralize various combinations of TGFβ1, 2 or 3. The primary panning did not yield any uniformly potent pan-isoform neutralizing antibodies; therefore, an antibody that displayed potent TGFβ 1, 2 inhibition, but more modest affinity versus TGFβ3, was affinity matured by shuffling with a light chain sub-library and further screening. This process yielded a high affinity pan-isoform neutralizing clone. Antibodies were analyzed and compared by binding affinity, as well as receptor and epitope competition by surface plasmon resonance methods. The antibodies were also shown to neutralize TGFβ effects in vitro in 3 assays: 1) interleukin (IL)-4 induced HT-2 cell proliferation; 2) TGFβ-mediated IL-11 release by A549 cells; and 3) decreasing SMAD2 phosphorylation in Detroit 562 cells. The antibodies' potency in these in vitro assays correlated well with their isoform-specific affinities. Furthermore, the ability of the affinity-matured clone to decrease tumor burden in a Detroit 562 xenograft study was superior to that of the parent clone. This affinity-matured antibody acts as a very potent inhibitor of all 3 main isoforms of TGFβ and may have utility for therapeutic intervention in human disease.

  3. L'accumulation des métaux lourds au niveau des cultures : Cas des ...

    African Journals Online (AJOL)

    Le Bassin de Sebou présente une importance socio-économique pour le Maroc. En effet, il est sujet de diverses utilisations ; eau potable, eau d'irrigation et eau industrielle. Toutefois, ce bassin subit des pressions multiples, notamment par la pollution métallique. Considérant le risque de bioaccumulation des métaux par ...

  4. PRONÓSTICO DE VENTAS: COMPARACIÓN DE PREDICCIÓN ENTRE REDES NEURONALES Y MÉTODO ESTADÍSTICO

    Directory of Open Access Journals (Sweden)

    S. Nojek

    2003-05-01

    -family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

    RESUMEN

    Actualmente es común que las empresas realicen pronósticos de ventas para poder planificar más acertadamente su producción. El objetivo de este trabajo consiste en estudiar la predicción de ventas mediante el uso de redes neuronales, comparar los resultados obtenidos con los pronósticos de un método estadístico clásico y establecer los entornos más adecuados para su uso.

    Palabras Clave: Pronostico de Ventas – Predicción basada en Redes Neuronales.

     

    ABSTRACT

    Companies usually need sales forecast for improving production planning. This research work pursues to study sales forecast based on neural networks and to compare this results with the ones based on classical statistical methods trying to specify the adequate business environment for using them

    Keywords: Sales Forecast – Forecasting based on Neural Networks

  5. Evolution of the cAMP-dependent protein kinase (PKA catalytic subunit isoforms.

    Directory of Open Access Journals (Sweden)

    Kristoffer Søberg

    Full Text Available The 3',5'-cyclic adenosine monophosphate (cAMP-dependent protein kinase, or protein kinase A (PKA, pathway is one of the most versatile and best studied signaling pathways in eukaryotic cells. The two paralogous PKA catalytic subunits Cα and Cβ, encoded by the genes PRKACA and PRKACB, respectively, are among the best understood model kinases in signal transduction research. In this work, we explore and elucidate the evolution of the alternative 5' exons and the splicing pattern giving rise to the numerous PKA catalytic subunit isoforms. In addition to the universally conserved Cα1/Cβ1 isoforms, we find kinase variants with short N-termini in all main vertebrate classes, including the sperm-specific Cα2 isoform found to be conserved in all mammals. We also describe, for the first time, a PKA Cα isoform with a long N-terminus, paralogous to the PKA Cβ2 N-terminus. An analysis of isoform-specific variation highlights residues and motifs that are likely to be of functional importance.

  6. Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.

    Science.gov (United States)

    Bhalla, Akhil; Chicka, Michael C; Chapman, Edwin R

    2008-08-01

    Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells is regulated by the Ca(2+)-binding protein synaptotagmin (syt) I. Sixteen additional isoforms of syt have been identified, but little is known concerning their biochemical or functional properties. Here, we assessed the abilities of fourteen syt isoforms to directly regulate SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor)-catalyzed membrane fusion. One group of isoforms stimulated neuronal SNARE-mediated fusion in response to Ca(2+), while another set inhibited SNARE catalyzed fusion in both the absence and presence of Ca(2+). Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion, further establishing PS and SNAREs as critical effectors for syt action. The ability of syt I to efficiently stimulate fusion was specific for certain SNARE pairs, suggesting that syts might contribute to the specificity of intracellular membrane fusion reactions. Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other.

  7. Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

    Science.gov (United States)

    Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

    2017-09-29

    Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

  8. Novel frataxin isoforms may contribute to the pathological mechanism of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Haiyan Xia

    Full Text Available Friedreich ataxia (FRDA is an inherited neurodegenerative disease caused by frataxin (FXN deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III, which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.

  9. Nesprin-2 epsilon: A novel nesprin isoform expressed in human ovary and Ntera-2 cells

    International Nuclear Information System (INIS)

    Lam, Le Thanh; Boehm, Sabrina V.; Roberts, Roland G.; Morris, Glenn E.

    2011-01-01

    Highlights: → A novel epsilon isoform of nesprin-2 has been discovered. → This 120 kDa protein was predicted by bioinformatic analysis, but has not previously been observed. → It is the main isoform expressed in a teratocarcinoma cell line and is also found in ovary. → Like other nesprins, it is located at the nuclear envelope. → We suggest it may have a role in very early development or in some ovary-specific function. -- Abstract: The nuclear envelope-associated cytoskeletal protein, nesprin-2, is encoded by a large gene containing several internal promoters that produce shorter isoforms. In a study of Ntera-2 teratocarcinoma cells, a novel isoform, nesprin-2-epsilon, was found to be the major mRNA and protein product of the nesprin-2 gene. Its existence was predicted by bioinformatic analysis, but this is the first direct demonstration of both the mRNA and the 120 kDa protein which is located at the nuclear envelope. In a panel of 21 adult and foetal human tissues, the nesprin-2-epsilon mRNA was strongly expressed in ovary but was a minor isoform elsewhere. The expression pattern suggests a possible link with very early development and a likely physiological role in ovary.

  10. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  11. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  12. Functional divergence of platelet protein kinase C (PKC) isoforms in thrombus formation on collagen.

    Science.gov (United States)

    Gilio, Karen; Harper, Matthew T; Cosemans, Judith M E M; Konopatskaya, Olga; Munnix, Imke C A; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D; Heemskerk, Johan W M; Poole, Alastair W

    2010-07-23

    Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent alpha-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCalpha and PKCbeta, whereas the novel isoform, PKC, negatively regulates these events. PKCdelta also negatively regulates thrombus formation but not alpha-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCalpha or PKCbeta showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKC. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen.

  13. Functional Divergence of Platelet Protein Kinase C (PKC) Isoforms in Thrombus Formation on Collagen*

    Science.gov (United States)

    Gilio, Karen; Harper, Matthew T.; Cosemans, Judith M. E. M.; Konopatskaya, Olga; Munnix, Imke C. A.; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D.; Heemskerk, Johan W. M.; Poole, Alastair W.

    2010-01-01

    Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent α-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCα and PKCβ, whereas the novel isoform, PKCθ, negatively regulates these events. PKCδ also negatively regulates thrombus formation but not α-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCα or PKCβ showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKCθ. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen. PMID:20479008

  14. Proteomic Analysis of Parkin Isoforms Expression in Different Rat Brain Areas.

    Science.gov (United States)

    D'Amico, Agata Grazia; Maugeri, Grazia; Reitano, Rita; Cavallaro, Sebastiano; D'Agata, Velia

    2016-10-01

    PARK2 gene's mutations are related to the familial form of juvenile Parkinsonism, also known as the autosomic recessive juvenile Parkinsonism. This gene encodes for parkin, a 465-amino acid protein. To date, a large number of parkin isoforms, generated by an alternative splicing mechanism, have been described. Currently, Gene Bank lists 27 rat PARK2 transcripts, which matches to 20 exclusive parkin alternative splice variants. Despite the existence of these isoforms, most of the studies carried out so far, have been focused only on the originally cloned parkin. In this work we have analyzed the expression profile of parkin isoforms in some rat brain areas including prefrontal cortex, hippocampus, substantia nigra and cerebellum. To discriminate among these isoforms, we detected their localization through the use of two antibodies that are able to identify different domains of the parkin canonical sequence. Our analysis has revealed that at least fourteen parkin isoforms are expressed in rat brain with a various distribution in the regions analyzed. Our study might help to elucidate the pathophysiological role of these proteins in the central nervous system.

  15. Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Xiaoling; Baird, Daniel; Bowen, Kimberly; Capka, Vladimir; Chen, Jinyun; Chenail, Gregg; Cho, YoungShin; Dooley, Julia; Farsidjani, Ali; Fortin, Pascal; Kohls, Darcy; Kulathila, Raviraj; Lin, Fallon; McKay, Daniel; Rodrigues, Lindsey; Sage, David; Touré, B. Barry; van der Plas, Simon; Wright, Kirk; Xu, Ming; Yin, Hong; Levell, Julian; Pagliarini, Raymond A. (Novartis)

    2017-03-01

    Oncogenic IDH1 and IDH2 mutations contribute to cancer via production of R-2-hydroxyglutarate (2-HG). Here, we characterize two structurally distinct mutant- and isoform-selective IDH1 inhibitors that inhibit 2-HG production. Both bind to an allosteric pocket on IDH1, yet shape it differently, highlighting the plasticity of this site. Oncogenic IDH1R132H mutation destabilizes an IDH1 “regulatory segment,” which otherwise restricts compound access to the allosteric pocket. Regulatory segment destabilization in wild-type IDH1 promotes inhibitor binding, suggesting that destabilization is critical for mutant selectivity. We also report crystal structures of oncogenic IDH2 mutant isoforms, highlighting the fact that the analogous segment of IDH2 is not similarly destabilized. This intrinsic stability of IDH2 may contribute to observed inhibitor IDH1 isoform selectivity. Moreover, discrete residues in the IDH1 allosteric pocket that differ from IDH2 may also guide IDH1 isoform selectivity. These data provide a deeper understanding of how IDH1 inhibitors achieve mutant and isoform selectivity.

  16. Expression of a novel cardiac-specific tropomyosin isoform in humans

    International Nuclear Information System (INIS)

    Denz, Christopher R.; Narshi, Aruna; Zajdel, Robert W.; Dube, Dipak K.

    2004-01-01

    Tropomyosins are a family of actin binding proteins encoded by a group of highly conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3, and TPM4, each of which is known to generate multiple isoforms by alternative splicing, promoters, and 3 ' end processing. TPM1 is the most versatile and encodes a variety of tissue specific isoforms. The TPM1 isoform specific to striated muscle, designated TPM1α, consists of 10 exons: 1a, 2b, 3, 4, 5, 6b, 7, 8, and 9a/b. In this study, using RT-PCR with adult and fetal human RNAs, we present evidence for the expression of a novel isoform of the TPM1 gene that is specifically expressed in cardiac tissues. The new isoform is designated TPM1κ and contains exon 2a instead of 2b. Ectopic expression of human GFP.TPM1κ fusion protein can promote myofibrillogenesis in cardiac mutant axolotl hearts that are lacking in tropomyosin

  17. Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage Mucor circinelloides.

    Science.gov (United States)

    Fernández Núñez, Lucas; Ocampo, Josefina; Gottlieb, Alexandra M; Rossi, Silvia; Moreno, Silvia

    2016-12-01

    Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal lineage Mucor. From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic subunits of PKA. From sequence alignment and structural prediction we conclude that the catalytic core of the isoforms is conserved, and the difference between them resides in their amino termini. This high number of isoforms is maintained in the subdivision Mucoromycotina. Each paralogue, when compared to the ones form other fungi is more homologous to one of its orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II in which fungal protein kinases have been classified. mRNA levels for each isoform were measured during aerobic and anaerobic growth. The expression of each isoform is differential and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944), the only cloned sequence available until now for a catalytic subunit of M. circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be measured for this protein nor predicted bioinformatically. It can thus be classified as a pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level in different stages of growth, and its deletion is lethal. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  18. MAPA distinguishes genotype-specific variability of highly similar regulatory protein isoforms in potato tuber.

    Science.gov (United States)

    Hoehenwarter, Wolfgang; Larhlimi, Abdelhalim; Hummel, Jan; Egelhofer, Volker; Selbig, Joachim; van Dongen, Joost T; Wienkoop, Stefanie; Weckwerth, Wolfram

    2011-07-01

    Mass Accuracy Precursor Alignment is a fast and flexible method for comparative proteome analysis that allows the comparison of unprecedented numbers of shotgun proteomics analyses on a personal computer in a matter of hours. We compared 183 LC-MS analyses and more than 2 million MS/MS spectra and could define and separate the proteomic phenotypes of field grown tubers of 12 tetraploid cultivars of the crop plant Solanum tuberosum. Protein isoforms of patatin as well as other major gene families such as lipoxygenase and cysteine protease inhibitor that regulate tuber development were found to be the primary source of variability between the cultivars. This suggests that differentially expressed protein isoforms modulate genotype specific tuber development and the plant phenotype. We properly assigned the measured abundance of tryptic peptides to different protein isoforms that share extensive stretches of primary structure and thus inferred their abundance. Peptides unique to different protein isoforms were used to classify the remaining peptides assigned to the entire subset of isoforms based on a common abundance profile using multivariate statistical procedures. We identified nearly 4000 proteins which we used for quantitative functional annotation making this the most extensive study of the tuber proteome to date.

  19. Terre des hommes

    CERN Multimedia

    Staff Association

    2012-01-01

    Transformez votre téléphone portable en geste de solidarité ! Collecte du 12 au 23 novembre 2012   Faites un geste simple et utile en déposant vos téléphones portables inutilisés dans les urnes installées dans les trois restaurants du CERN. En Suisse, une personne change tous les 12 à 18 mois de téléphone portable. La plupart de nos vieux appareils sont simplement laissés à l’abandon avec comme seule fonction de parer une éventuelle panne à venir. On  estime ainsi que 8 millions de portables sont inutilisés, alors qu'entre 30 et 50% peuvent être réutilisés. L'action Solidarcomm leur offre une deuxième vie ! Terre des Hommes Suisse, dans le cadre de la campagne Solidarcomm, collecte et valorise vos téléphones inutilis&...

  20. Onlinespieler abseits des Mainstreams

    Directory of Open Access Journals (Sweden)

    Harald Baumgartlinger

    2012-12-01

    Full Text Available MMO(RPGs „Massively Multiplayer Online (Role-Playing Games“ nehmen einen Sonderstatus unter den Onlinespielen ein, welcher durch den wachsenden wirtschaftlichen Erfolg, insbesondere durch den „breakthrough hit“ (Duchenaut et al. 2006: 407 World of Warcraft (WoW, auch an Bedeutung für die Medien- und Kommunikationswissenschaft gewinnt (vgl. Inderst 2009: 15; vgl. Seifert/Jöckel 2008: 297. Der Primus des Genres, WoW, repräsentiert gemeinsam mit einigen nahezu identen Titeln insgesamt 85 Prozent der gespielten MMOGs (vgl. Williams et al. 2008: 999. Daher befasst sich auch die Mehrheit der vorliegenden Studien mit eben diesen Spielen. Neue Formen von MMO(Gs können jedoch zu ebenso neuartigen Spielerfahrungen führen und damit unterschiedliche Nutzungsmotive befriedigen (vgl. Seifert/Jöckel 2008: 309 und folglich zu einem gänzlich anderen Spielerleben führen. Während im Mainstream die kooperativen Spielerbeziehungen überwiegen, dominiert in Darkfall Online der soziale Wettbewerb. Der von Williams et al. 2008 verwendete Fragebogen diente als Rohling für die Kreation eines für die speziellen Anforderungen adaptierten Erhebungstools zur Erforschung der Spielertypologie und der Motive der Darkfall-Online-SpielerInnen. Die in der Onlinebefragung (N = 506 gesammelten Daten belegen, dass sich sowohl die Spielerdemographie, als auch die Motive der Spieler von den Mainstream MMOs unterscheiden. Zudem konnten realweltliche Eigenschaften der Spieler als signifikante Einflussfaktoren für die Spielzuwendung identifiziert werden.

  1. The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

    Science.gov (United States)

    Appukuttan, Binoy; McFarland, Trevor J.; Stempel, Andrew; Kassem, Jean B.; Hartzell, Matthew; Zhang, Yi; Bond, Derek; West, Kelsey; Wilson, Reid; Stout, Andrew; Pan, Yuzhen; Ilias, Hoda; Robertson, Kathryn; Klein, Michael L.; Wilson, David; Smith, Justine R.; Stout, J. Timothy

    2012-01-01

    Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases. PMID:22761647

  2. Gyrodactylidae et Gyrodactylose des Salmonidae

    Directory of Open Access Journals (Sweden)

    MALMBERG G.

    1993-01-01

    Full Text Available Vingt et une espèces de Gyrodactylus de Salmonidae arrangées en six groupes sont présentées. Les observations concernant ces espèces dans les milieux naturels et en pisciculture sont résumées. Sur la base de données générales relatives aux espèces de Gyrodactylus en milieu naturel en Scandinavie et Baltique, les observations biologiques, écologiques et comportementales de G. salaris Malmberg, 1957 et G. derjavini MALMBERG et MALMBERG (1987 des salmonidae sauvages des rivières norvégiennes et suédoises sont présentées. La viviparité unique, la reproduction asexuée et sexuée et le pouvoir de reproduction chez les Gyrodactylus sont développés. La Gyrodactylose à G. salaris est abordée en milieu naturel, dans les rivières norvégiennes et en pisciculture, en Suède et au Danemark. L'étude ultrastructurale des blessures causées par G. salaris ainsi que les résultats expérimentaux sur les espèces norvégiennes et canadiennes sont présentés. La distribution géographique naturelle des Salmonidae, les modifications liées à l'homme et à l'activité économique ainsi que les Salmonidae élevés sont revus. La présence de six groupes d'espèces de Gyrodactylus en Amérique du Nord et Eurasie est discutée en fonction de la distribution géographique des espèces hôtes. Il est souligné qu'une propagation intercontinentale des espèces de Gyrodactylus de Salmonidae a dû être impossible à cause de leur origine limnique d'une part et de la salinité élevée des océans atlantique et pacifique d'autre part. Les exigences micro et macro environnementales des espèces sont discutées dans les conditions naturelles et les variations saisonnières, préférendums et tolérances du parasitisme sont signalés. L'effet des conditions de pisciculture sur les espèces de Gyrocactylus sont discutées : la capacité reproductrice et de propagation ainsi que la spécificité — stricte dans la nature — peuvent être influenc

  3. Current algebra; Algebre des courants

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, M [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The first three chapters of these lecture notes are devoted to generalities concerning current algebra. The weak currents are defined, and their main properties given (V-A hypothesis, conserved vector current, selection rules, partially conserved axial current,...). The SU (3) x SU (3) algebra of Gell-Mann is introduced, and the general properties of the non-leptonic weak Hamiltonian are discussed. Chapters 4 to 9 are devoted to some important applications of the algebra. First one proves the Adler- Weisberger formula, in two different ways, by either the infinite momentum frame, or the near-by singularities method. In the others chapters, the latter method is the only one used. The following topics are successively dealt with: semi leptonic decays of K mesons and hyperons, Kroll- Ruderman theorem, non leptonic decays of K mesons and hyperons ( {delta}I = 1/2 rule), low energy theorems concerning processes with emission (or absorption) of a pion or a photon, super-convergence sum rules, and finally, neutrino reactions. (author) [French] La premiere partie de ce cours (trois premiers chapitres), traite des generalites concernant l'algebre de courants. Apres une definition rapide des courants faibles et un rappel de leurs proprietes (hypothese V-A, conservation du courant vecteur, regles de selection, courant axial partiellement conserve,...), l'on introduit l'algebre de Gell-Mann SU (3) x SU (3), et discute les proprietes generales de l'Hamiltonien faible non leptonique. Les chapitres IV a IX sont consacres a des applications importantes de l'algebre des courants. En premier lieu l'on demontre la formule de Adler et Weisberger, par deux methodes differentes, celle dite du repere de moment infini et celle des singularites proches. Cette derniere est seule utilisee dans la suite. Puis, l'on traite successivement les problemes suivants: desintegrations semi-leptoniques des mesons K et des hyperons, theoreme de Kroll-Ruderman, desintegrations non leptoniques des mesons

  4. Aplicación de análisis de conglomerados y redes neuronales artificiales para la clasificación y selección de candidatos a residencias médicas

    Directory of Open Access Journals (Sweden)

    Raúl A. Borracci

    Full Text Available Introducción: Los programas educacionales han recurrido a distintos modelos de regresión lineal múltiple, de selección asistida por computadora y más recientemente, de redes neuronales artificiales para la confección de listados preliminares de mérito entre los postulantes a la residencia. Objetivo: evaluar y rediseñar un sistema para la selección y clasificación de aspirantes a un programa de residencias universitarias por medio de la aplicación de modelos de análisis multivariante y de redes neuronales artificiales. Material y Método: El diseño consistió en un estudio retrospectivo-transversal, realizado en un hospital universitario. Se evaluó una muestra al azar de 213 aspirantes a un programa de residencias médicas universitarias teniendo en cuenta el promedio de la carrera de grado, el resultado del examen de ingreso a la residencia, los antecedentes curriculares y biográficos, el internado y el puntaje de las entrevistas. Se aplicó un análisis de conglomerados jerárquico (clúster análisis para la clasificación y selección de los candidatos en un orden de mérito en base a los puntajes estandarizados de las 5 variables. Resultados: El análisis de conglomerados jerárquico clasificó 209 aspirantes en 12 conglomerados en base al promedio estandarizado de los valores obtenidos de las 5 variables. Este análisis se usó para construir una clasificación descriptiva de los grupos y una lista final por mérito de acuerdo a la posición relativa de cada candidato por encima o debajo de los puntajes promedios. Se imitó la solución de conglomerados por medio de una red perceptrón multicapa con una sensibilidad y especificidad de 94.1 y 99.1% respectivamente. Conclusiones: El análisis de conglomerados jerárquico fue un método útil y novedoso para clasificar una muestra de aspirantes a la residencia en conglomerados de acuerdo a la posición relativa de sus puntajes estandarizados por encima o por debajo de la media

  5. ETUDE DE LA DISTRIBUTION DES CATIONS ECHANGEABLES

    African Journals Online (AJOL)

    SEI Joseph

    pollution. L'objectif du présent travail est l'étude de la qualité des eaux superficielles et souterraines pour évaluer le degré de pollution provenant des lixiviats de la décharge et des cours d'eaux dans lesquels les ..... Les métaux lourds dosés ont montré une pollution métallique des eaux souterraine par rapport à la norme.

  6. ETUDE DE LA DISTRIBUTION DES CATIONS ECHANGEABLES

    African Journals Online (AJOL)

    SEI Joseph

    D'autre part, à cause de la corrélation directe entre l'étendue des inondations et les quantités de poissons et de pâturages fournies par la plaine, il y a eu dégradation des ... aux changements climatiques en zone sahélienne du Cameroun. Un des objectifs de notre étude était de préciser le comportement des agriculteurs ...

  7. Predicción por redes neuronales artificiales de la calidad fisicoquímica de vinagre de melaza de caña por efecto de tiempo-temperatura de alimentación a evaporador-destilador flash

    Directory of Open Access Journals (Sweden)

    Víctor Vásquez V.

    2010-01-01

    Full Text Available Se predijo por Redes Neuronales Artificiales (RNA importantes características fisicoquímicas de vinagre de melaza: pH, densidad, acidez total, etanol, aldehídos totales y furfural; obtenidas mediante operaciones de evaporación flash y clarificación por destilación flash. Melaza fermentada por vía alcohólica y acética, fue alimentada a un evaporador flash a cuatro temperaturas (61, 66, 71 y 76 °C y tres tiempos (25, 35 y 45 min. La predicción se realizó con dos redes: RNA-A y RNA-B, ambas con buen desempeño. La RNA-A fue del tipo feedforward (FF, con algoritmos de entrenamiento Backpropagation (BP y ajuste de pesos Levenberg-Marquardt (LM, topología: 6 entradas (datos de las operaciones de evaporación-destilación flash, 7 salidas lineales (características fisicoquímicas, 9 neuronas tangente sigmoidales en 1 capa oculta, coeficiente de momento 0.5, tasa de aprendizaje 0.01, meta del error 0.0001 y 20 etapas de entrenamiento. La RNA-A mostró mejor desempeño que un modelo estadístico de primer orden. La RNA-B igualmente FF, con algoritmos BP y LM, topología: 2 entradas (datos de la evaporación flash, 7 salidas lineales (características fisicoquímicas, 84 neuronas logaritmo sigmoidales en 1 capa oculta, coeficiente de momento 0.5, tasa de aprendizaje 0.01, meta del error 0.0001 y 300 etapas de entrenamiento. La RNA-B mostró igual capacidad predictiva que un modelo estadístico de primer orden con interacción de términos.

  8. Modelamiento matemático y por redes neuronales artificiales del crecimiento de Spirulina sp. en fotobiorreactor con fuente de luz fluorescente e iluminación en estado sólido

    Directory of Open Access Journals (Sweden)

    Víctor Vásquez-Villalobos

    2013-01-01

    Full Text Available Se evaluaron los modelos matemáticos de Gompertz y logístico en la cinética de crecimiento de Spirulina sp., los cuales fueron comparados con un modelamiento por Redes Neuronales Artificiales Backpropagation (RNA-BP. La Spirulina fue cultivada en un fotobiorreactor de laboratorio aireado (3 L/min de 500 mL, con iluminación fluorescente de 40W y en Estado Sólido (LED-Light Emitting Diode de 1W; obteniendo con ambos sistemas 11,0 klx. La iluminación LED, permitió obtener un valor elevado de biomasa (ɑ de 0,90 , en comparación con la obtenida con iluminación fluorescente de 0,82; así como una mayor velocidad de crecimiento μ=0,63 h-1, precedida de un menor tiempo de latencia λ=0,34 h. La RNA-BP mostró buena precisión con respecto al modelo corregido de Gompertz I, tanto para el caso del cultivo de Spirulina sp. con iluminación fluorescente y con LED, mostrando coeficientes de correlación (R del orden de 0,993 y 0,994 respectivamente, con respecto a los datos experimentales. Resulta ventajoso el modelamiento a través del modelo corregido de Gompertz I, porque además de valores de R de 0,987 y 0,990 en los cultivos de Spirulina sp. Con iluminación fluorescente y con LED respectivamente, permite obtener los parámetros de la cinética de crecimiento de manera directa.

  9. Predicción del color y contenido de humedad en café cerezo mediante redes neuronales y regresión de mínimos cuadrados parciales

    Directory of Open Access Journals (Sweden)

    Wilson Manuel Castro Silupu

    2015-12-01

    Full Text Available La presente investigación se enfocó en el desarrollo de modelos de predicción del color en coordenadas CIELab y el contenido de humedad de café cerezo mediante la tecnología de imágenes hiperespectrales; comparando el ajuste por un modelo de regresión lineal múltiple – PLSR (Partialleastsquareregression y un modelo no lineal (ANN – artiftial neural network. La muestra se conformó de 200 granos de café cerezo en diferentes estados de madurez, dividiéndola en 120 granos para calibración y 80 de validación.La  muestra fue caracterizada mediante colorimetría en el espacio CIELab y determinación de la humedad. Posteriormente se adquirieron imágenes hiperespectrales de cada granos y se almacenaron en formato *.bil. El procesamiento de las imágenes se realizó mediante un sistema desarrollado e implementado en el software matemático Matlab 2010a, mediante funciones *.m e interfaces de usuario (GUIs. Se desarrollaron modelos de ajuste para cada una de las coordenadas de color y el contenido de humedad, calculándose los coeficientes de correlación en calibración y validación. Los resultados mostraron que las redes neuronales tienen un mayor ajuste en calibración con coeficientes de correlación superiores a 0,90 mientras que el PLSR genero coeficientes entre 0,42 y 0,48.

  10. Architecture, des normes et des systèmes d'information libres, phase ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Architecture, des normes et des systèmes d'information libres, phase II (OASIS II) - Renforcement des capacités dans l'ensemble de l'Afrique. Sur presque tout le continent africain, la prestation des services de santé est limitée en raison des maigres ressources disponibles et de la charge de morbidité de plus en plus ...

  11. Prise en charge des urgences au service d'accueil des urgences ...

    African Journals Online (AJOL)

    Introduction: La prise en charge des patients dans les services d'accueil des urgences est une des meilleures vitrines d'un système de santé. En Afrique subsaharienne, la gestion des urgences se heurte à des difficultés humaines et matérielles. Le but de ce travail était d'évaluer les difficultés de prise en charge au Service ...

  12. Differential expression of a new isoform of DLG2 in renal oncocytoma

    International Nuclear Information System (INIS)

    Zubakov, Dmitry; Stupar, Zorica; Kovacs, Gyula

    2006-01-01

    Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type. In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis. We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour. The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma

  13. The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells.

    Science.gov (United States)

    Jerrell, Rachel J; Leih, Mitchell J; Parekh, Aron

    2017-06-26

    Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.

  14. Branchial Expression Patterns of Claudin Isoforms in Atlantic Salmon During Seawater Acclimation and Smoltification

    DEFF Research Database (Denmark)

    Tipsmark, Christian K; Kiilerich, Pia; Nilsen, Tom O

    2008-01-01

    in epithelia. We identified Atlantic salmon genes belonging to the claudin family by screening expressed sequence tag libraries available at NCBI and classification was performed with aid of maximum likelihood and neighbour-joining analysis. In gill libraries, five isoforms (10e, 27a, 28a, 28b and 30) were...... present and QPCR analysis confirmed tissue-specific expression in gill when compared to kidney, intestine, heart, muscle, brain and liver. Expression patterns during acclimation of freshwater salmon to seawater (SW) and during the smoltification process were examined. Acclimation to SW reduced...... induced no significant changes in expression of the other isoforms. This study demonstrates the expression of an array of salmon claudin isoforms and shows that SW acclimation involves inverse regulation, in the gill, of claudin 10e versus claudin 27a and 30. It is possible, that claudin 10e...

  15. Evaluer des études de gestion des entreprises : combiner des éléments principales avec des éléments pratiques

    NARCIS (Netherlands)

    Pennink, B.J.W.

    2002-01-01

    Evaluer la recherche de gestion demande une combinaison des critères classiques et des critères pratiques. Par cette combinaison il est possible de trouver une réponse cerrecte concernant la validité et l'effet de la recherche. Dans cet article nous allons décrire comment une combinaison des

  16. Perceptions locales de la manifestation des changements ...

    African Journals Online (AJOL)

    SARAH

    . PRPR. ERMA. DC. UD cluster 1 cluster 2. Pauvres. Riches et moyens. Figure 4. Positionnement des classes d'impacts socio-économiques des changements climatiques dans un système d'axes de l'analyse factorielle des ...

  17. Migration transnationale des Vietnamiennes en Asie | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Souvent, cependant, les pays d'origine ne disposent pas des politiques ni des lois ayant force exécutoire qui permettraient d'assurer des pratiques d'embauche ... Women's movements in India are struggling to address problems arising from rapidly changing social relations and vulnerabilities associated with, among other ...

  18. Innovation, apprentissage et cadres institutionnels dans des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Trois secteurs de transformation des ressources naturelles - ceux des pâtes et ... devrait déboucher sur des recommandations concrètes pour l'élaboration de ... bibliothèque de ressources aideront à améliorer les systèmes d'information et ...

  19. Aux origines des Jeux olympiques.

    Directory of Open Access Journals (Sweden)

    Isabelle Debilly

    2005-11-01

    Full Text Available Si les Jo modernes sont régulièrement sous les feux de l’actualité, soit par la répétition temporelle des Olympiades elle-même, soit par les enjeux économiques féroces qui découlent du choix des lieux, ceux de l’Antiquité sont en général cantonnés au domaine scolaire ou universitaire. Néanmoins, ils bénéficient tous les quatre ans d`un éclairage médiatique. L’ouvrage Olympie. La victoire pour les dieux est au croisement des deux domaines. En effet, écrit par un ...

  20. Romagnat – Bois des Goules

    OpenAIRE

    Leguet, Daniel

    2014-01-01

    Lien Atlas (MCC) : http://atlas.patrimoines.culture.fr/atlas/trunk/index.php?ap_theme=DOM_2.01.02&ap_bbox=3.027;45.698;3.133;45.745 La parcelle prospectée se situe sur le flanc nord du col des Goules, passage traditionnel vers l’oppidum de Gergovie, dans un profond thalweg emprunté jadis par un chemin descendant sur Romagnat. Sur la pente actuelle entièrement boisée, on trouve des sentiers récents et des pistes de motocross. C’est sur l’une de ces dernières que nous avions recueilli un poids ...

  1. Different characteristics and nucleotide binding properties of inosine monophosphate dehydrogenase (IMPDH isoforms.

    Directory of Open Access Journals (Sweden)

    Elaine C Thomas

    Full Text Available We recently reported that Inosine Monophosphate Dehydrogenase (IMPDH, a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, clustered into macrostructures in response to decreased nucleotide levels and that there were differences between the IMPDH isoforms, IMPDH1 and IMPDH2. We hypothesised that the Bateman domains, which are present in both isoforms and serve as energy-sensing/allosteric modules in unrelated proteins, would contribute to isoform-specific differences and that mutations situated in and around this domain in IMPDH1 which give rise to retinitis pigmentosa (RP would compromise regulation. We employed immuno-electron microscopy to investigate the ultrastructure of IMPDH macrostructures and live-cell imaging to follow clustering of an IMPDH2-GFP chimera in real-time. Using a series of IMPDH1/IMPDH2 chimera we demonstrated that the propensity to cluster was conferred by the N-terminal 244 amino acids, which includes the Bateman domain. A protease protection assay suggested isoform-specific purine nucleotide binding characteristics, with ATP protecting IMPDH1 and AMP protecting IMPDH2, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting IMPDH catalytic activity. ATP binding to IMPDH1 was confirmed in a nucleotide binding assay. The RP-causing mutation, R224P, abolished ATP binding and nucleotide protection and this correlated with an altered propensity to cluster. Collectively these data demonstrate that (i the isoforms are differentially regulated by AMP and ATP by a mechanism involving the Bateman domain, (ii communication occurs between the Bateman and catalytic domains and (iii the RP-causing mutations compromise such regulation. These findings support the idea that the IMPDH isoforms are subject to distinct regulation and that regulatory defects contribute to human disease.

  2. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

    Directory of Open Access Journals (Sweden)

    Kristin R Wildsmith

    Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

  3. Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation

    Science.gov (United States)

    Seeger, Tanja; Hart, Melanie; Patarroyo, Manuel; Rolauffs, Bernd; Aicher, Wilhelm K.; Klein, Gerd

    2015-01-01

    Multipotent mesenchymal stromal cells (MSCs) are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM) which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521) showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells. PMID:26406476

  4. Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation.

    Directory of Open Access Journals (Sweden)

    Tanja Seeger

    Full Text Available Multipotent mesenchymal stromal cells (MSCs are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521 showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells.

  5. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

    Science.gov (United States)

    Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

    2017-07-01

    Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

  6. GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation.

    Science.gov (United States)

    Pardo, M; Abrial, E; Jope, R S; Beurel, E

    2016-03-01

    Abnormally active glycogen synthase kinase-3 (GSK3) contributes to pathological processes in multiple psychiatric and neurological disorders. Modeled in mice, this includes increasing susceptibility to dysregulation of mood-relevant behaviors, impairing performance in several cognitive tasks and impairing adult hippocampal neural precursor cell (NPC) proliferation. These deficits are all evident in GSK3α/β knockin mice, in which serine-to-alanine mutations block the inhibitory serine phosphorylation regulation of both GSK3 isoforms, leaving GSK3 hyperactive. It was unknown if both GSK3 isoforms perform redundant actions in these processes, or if hyperactivity of one GSK3 isoform has a predominant effect. To test this, we examined GSK3α or GSK3β knockin mice in which only one isoform was mutated to a hyperactive form. Only GSK3β, not GSK3α, knockin mice displayed heightened vulnerability to the learned helplessness model of depression-like behavior. Three cognitive measures impaired in GSK3α/β knockin mice showed differential regulation by GSK3 isoforms. Novel object recognition was impaired in GSK3β, not in GSK3α, knockin mice, whereas temporal order memory was not impaired in GSK3α or GSK3β knockin mice, and co-ordinate spatial processing was impaired in both GSK3α and GSK3β knockin mice. Adult hippocampal NPC proliferation was severely impaired in GSK3β knockin mice, but not impaired in GSK3α knockin mice. Increased activity of GSK3β, in the absence of overexpression or disease pathology, is sufficient to impair mood regulation, novel object recognition and hippocampal NPC proliferation, whereas hyperactive GSK3α individually does not impair these processes. These results show that hyperactivity of the two GSK3 isoforms execute non-redundant effects on these processes. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  7. BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer

    Science.gov (United States)

    Link, Petra A.; Zhang, Wa; Odunsi, Kunle; Karpf, Adam R.

    2013-01-01

    Cancer germline (CG) genes are normally expressed in germ cells and aberrantly expressed in a variety of cancers; their immunogenicity has led to the widespread development of cancer vaccines targeting these antigens. BORIS/CTCFL is an autosomal CG antigen and promising cancer vaccine target. BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation. We have previously shown that BORIS is expressed in epithelial ovarian cancer (EOC) and that its expression coincides with promoter and global DNA hypomethylation. Recently, 23 different BORIS mRNA variants have been described, and have been functionally grouped into six BORIS isoform families (sf1–sf6). In the present study, we have characterized the expression of BORIS isoform families in normal ovary (NO) and EOC, the latter of which were selected to include two groups with widely varying global DNA methylation status. We find selective expression of BORIS isoform families in NO, which becomes altered in EOC, primarily by the activation of BORIS sf1 in EOC. When comparing EOC samples based on methylation status, we find that BORIS sf1 and sf2 isoform families are selectively activated in globally hypomethylated tumors. In contrast, CTCF is downregulated in EOC, and the ratio of BORIS sf1, sf2, and sf6 isoform families as a function of CTCF is elevated in hypomethylated tumors. Finally, the expression of all BORIS isoform families was induced to varying extents by epigenetic modulatory drugs in EOC cell lines, particularly when DNMT and HDAC inhibitors were used in combination. PMID:23390377

  8. Expression of Metallothionein and Vascular Endothelial Growth Factor Isoforms in Breast Cancer Cells.

    Science.gov (United States)

    Wierzowiecka, Barbara; Gomulkiewicz, Agnieszka; Cwynar-Zajac, Lucja; Olbromski, Mateusz; Grzegrzolka, Jedrzej; Kobierzycki, Christopher; Podhorska-Okolow, Marzenna; Dziegiel, Piotr

    2016-01-01

    Metallothioneins (MTs) are low-molecular-weight and cysteine-rich proteins that bind heavy metal ions and oxygen-free radicals. MTs are commonly expressed in various tissues of mammals and are involved in regulation of cell proliferation and differentiation, and may be engaged in angiogenesis. Expression of MTs has been studied in many cancer types, especially breast cancer. The research results indicate that MTs may play important, although not yet fully known, roles in cancer angiogenesis. The aim of this study was to analyze the level of gene expression of selected MT isoforms induced with zinc ions in correlation with vascular endothelial growth factor (VEGF) isoforms in in vitro models of breast cancer. The studies were carried out in three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231). An epithelial cell line derived from normal breast tissue (Me16c) was used as a control. The levels of expression of selected MT isoforms and selected genes involved in angiogenesis were studied with real-time PCR. Expression of different MT isoforms was induced by zinc ions to differing degrees in individual breast cancer cell lines. An increase in the expression of some MT isoforms was associated with a slight increase in the level of expression of VEGFA. The research results may indicate certain correlation between an increased expression of selected MT isoforms and a pro-angiogenic factor VEGF in specific types of breast cancer cells. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

    Science.gov (United States)

    Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan

    2015-01-01

    Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.

  10. Transcriptome-wide identification and characterization of CAD isoforms specific for podophyllotoxin biosynthesis from Podophyllum hexandrum.

    Science.gov (United States)

    Bhattacharyya, Dipto; Hazra, Saptarshi; Banerjee, Anindyajit; Datta, Riddhi; Kumar, Deepak; Chakrabarti, Saikat; Chattopadhyay, Sharmila

    2016-09-01

    Podophyllotoxin (ptox) is a therapeutically important lignan derived from Podophyllum hexandrum and is used as a precursor for the synthesis of anticancer drugs etoposide, teniposide and etopophose. In spite of its enormous economic significance, genomic information on this endangered medicinal herb is scarce. We have performed de novo transcriptome analysis of methyl jasmonate (MeJA)-treated P. hexandrum cell cultures exhibiting enhanced ptox accumulation. The results revealed the maximum up-regulation of several isoforms of cinnamyl alcohol dehydrogenase (CAD). CAD catalyzes the synthesis of coniferyl alcohol and sinapyl alcohol from coniferaldehyde (CAld) and sinapaldehyde respectively. Coniferyl alcohol can produce both lignin and lignan while sinapyl alcohol produces only lignin. To isolate the CAD isoforms favoring ptox, we deduced full length cDNA sequences of four CAD isoforms: PhCAD1, PhCAD2, PhCAD3 and PhCAD4 from the contigs of the transcriptome data. In vitro enzyme assays indicated a higher affinity for CAld over sinapaldehyde for each isoform. In silico molecular docking analyses also suggested that PhCAD3 has a higher binding preference with CAld over sinapaldehyde, followed by PhCAD4, PhCAD2, and PhCAD1, respectively. The transgenic cell cultures overexpressing these isoforms independently revealed that PhCAD3 favored the maximum accumulation of ptox as compared to lignin followed by PhCAD4 and PhCAD2, whereas, PhCAD1 favored both equally. Together, our study reveals transcriptome-wide identification and characterization of ptox specific CAD isoforms from P. hexandrum. It provides a useful resource for future research not only on the ptox biosynthetic pathway but on overall P. hexandrum, an endangered medicinal herb with immense therapeutic importance.

  11. The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

    Directory of Open Access Journals (Sweden)

    Lili Li

    Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

  12. Crystal structures of a halophilic archaeal malate synthase from Haloferax volcanii and comparisons with isoforms A and G

    Science.gov (United States)

    2011-01-01

    Background Malate synthase, one of the two enzymes unique to the glyoxylate cycle, is found in all three domains of life, and is crucial to the utilization of two-carbon compounds for net biosynthetic pathways such as gluconeogenesis. In addition to the main isoforms A and G, so named because of their differential expression in E. coli grown on either acetate or glycolate respectively, a third distinct isoform has been identified. These three isoforms differ considerably in size and sequence conservation. The A isoform (MSA) comprises ~530 residues, the G isoform (MSG) is ~730 residues, and this third isoform (MSH-halophilic) is ~430 residues in length. Both isoforms A and G have been structurally characterized in detail, but no structures have been reported for the H isoform which has been found thus far only in members of the halophilic Archaea. Results We have solved the structure of a malate synthase H (MSH) isoform member from Haloferax volcanii in complex with glyoxylate at 2.51 Å resolution, and also as a ternary complex with acetyl-coenzyme A and pyruvate at 1.95 Å. Like the A and G isoforms, MSH is based on a β8/α8 (TIM) barrel. Unlike previously solved malate synthase structures which are all monomeric, this enzyme is found in the native state as a trimer/hexamer equilibrium. Compared to isoforms A and G, MSH displays deletion of an N-terminal domain and a smaller deletion at the C-terminus. The MSH active site is closely superimposable with those of MSA and MSG, with the ternary complex indicating a nucleophilic attack on pyruvate by the enolate intermediate of acetyl-coenzyme A. Conclusions The reported structures of MSH from Haloferax volcanii allow a detailed analysis and comparison with previously solved structures of isoforms A and G. These structural comparisons provide insight into evolutionary relationships among these isoforms, and also indicate that despite the size and sequence variation, and the truncated C-terminal domain of the H

  13. Effect of renal replacement therapy on retinol-binding protein 4 isoforms

    DEFF Research Database (Denmark)

    Frey, Simone K; Henze, Andrea; Nagl, Britta

    2009-01-01

    Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney dis...... diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms....

  14. Protein kinase C isoforms at the neuromuscular junction: localization and specific roles in neurotransmission and development.

    Science.gov (United States)

    Lanuza, Maria A; Santafe, Manel M; Garcia, Neus; Besalduch, Núria; Tomàs, Marta; Obis, Teresa; Priego, Mercedes; Nelson, Phillip G; Tomàs, Josep

    2014-01-01

    The protein kinase C family (PKC) regulates a variety of neural functions including neurotransmitter release. The selective activation of a wide range of PKC isoforms in different cells and domains is likely to contribute to the functional diversity of PKC phosphorylating activity. In this review, we describe the isoform localization, phosphorylation function, regulation and signalling of the PKC family at the neuromuscular junction. Data show the involvement of the PKC family in several important functions at the neuromuscular junction and in particular in the maturation of the synapse and the modulation of neurotransmission in the adult. © 2013 Anatomical Society.

  15. VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A

    Directory of Open Access Journals (Sweden)

    Pio Ruben

    2010-12-01

    Full Text Available Abstract Background Different isoforms of VEGF-A (mainly VEGF121, VEGF165 and VEGF189 have been shown to display particular angiogenic properties in the generation of a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms, designated as VEGFxxxb, generated through alternative splicing, have been described. Previous studies have suggested that these isoforms may inhibit angiogenesis. In the present work we have produced recombinant VEGF121/165b proteins in the yeast Pichia pastoris and constructed vectors to overexpress these isoforms and assess their angiogenic potential. Results Recombinant VEGF121/165b proteins generated either in yeasts or mammalian cells activated VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than VEGF165. Furthermore, treatment of endothelial cells with VEGF121/165b increased cell proliferation compared to untreated cells, although such stimulation was lower than that induced by VEGF165. Moreover, in vivo angiogenesis assays confirmed angiogenesis stimulation by VEGF121/165b isoforms. A549 and PC-3 cells overexpressing VEGF121b or VEGF165b (or carrying the PCDNA3.1 empty vector, as control and xenotransplanted into nude mice showed increased tumor volume and angiogenesis compared to controls. To assess whether the VEGFxxxb isoforms are differentially expressed in tumors compared to healthy tissues, immunohistochemical analysis was conducted on a breast cancer tissue microarray. A significant increase (p xxxb and total VEGF-A protein expression in infiltrating ductal carcinomas compared to normal breasts was observed. A positive significant correlation (r = 0.404, p = 0.033 between VEGFxxxb and total VEGF-A was found. Conclusions Our results demonstrate that VEGF121/165b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A. In addition, VEGFxxxb isoforms are up-regulated in breast cancer in comparison with non malignant breast tissues. These results are to be taken

  16. Cardiotoxicité des psychotropes

    OpenAIRE

    TAHIRI, Abdallah

    2013-01-01

    Même à dose thérapeutique, les médicaments psychotropes sont susceptibles d'engendrer des troubles du rythme cardiaque graves avec risque létal concourant à expliquer la pré valence de la mort subite dans la population psychiatrique. Les situations cliniques à risque telles que poly médication (des psychotropes entre eux ou d'un psychotrope avec un non psychotrope allongeur de QTc), interactions médicamenteuses aussi bien pharmacodynamiques que pharmacocinétiques, traitement pa...

  17. Tombes et cimetières éthiopiens : des rois, des saints, des anonymes1

    OpenAIRE

    Derat, Marie-Laure

    2009-01-01

    L’histoire des tombes et cimetières éthiopiens, dans la longue durée, en est encore à ses balbutiements. Si les tombes des saints et des rois nous sont un peu mieux connus grâce à des textes témoignant à la fois des enjeux entourant les sépultures de ces personnages hors du commun et des soins apportés à leur inhumation, en revanche, les cimetières ordinaires échappent encore largement à l’enquête, en grande partie parce que le commun des mortels est inhumé dans l’anonymat et dans un grand dé...

  18. Traits morphologiques des graines et vigueur des jeunes plants de ...

    African Journals Online (AJOL)

    écologique du Sénégal afin de pouvoir sélectionner une meilleure semence qui sera destinée aux programmes de développement des énergies renouvelables. Morphological traits of seeds and seedling vigor of two sources of Jatropha curcas L. in ...

  19. Traits morphologiques des graines et vigueur des jeunes plants de ...

    African Journals Online (AJOL)

    SARAH

    écologique du Sénégal afin de pouvoir sélectionner une meilleure semence qui sera destinée aux programmes de développement des énergies renouvelables. Journal of Applied Biosciences 88:8249– 8255. ISSN 1997–5902 ...

  20. Original Paper Dynamique des peuplements des Parcelles d'Essais ...

    African Journals Online (AJOL)

    permanentes (PFTP) à Bensékou visait à évaluer la dynamique de la population de ... est alors important de mettre en œuvre une sensibilisation de la population locale sur les mérites de la gestion ..... contrôle des PES se sont encore montré.

  1. Evaluation des conditions de germination des noyaux de Grewia ...

    African Journals Online (AJOL)

    personnel

    31 janv. 2014 ... 1Laboratoire de Physiologie et Production Végétales, Université Marien NGOUABI,. Faculté des Sciences et Techniques, BP.69. Brazzaville, Republique du Congo. 2Ecole Nationale Supérieure d'Agronomie et Forestérie, Université Marien NGOUABI,. BP. 69. Brazzaville, Republique du Congo.

  2. La maison des mathématiques

    CERN Document Server

    Villani, Cédric; Moncorgé, Vincent

    2014-01-01

    Comment travaillent les mathématiciens ? C'est peut-être en se promenant dans les couloirs de la première des " maisons des mathématiques " de France, l'institut Henri Poincaré, que l'on trouvera quelques réponses. Le mathématicien Cédric Villani et le physicien Jean-Philippe Uzan nous invitent à découvrir cette discipline et ses acteurs. Au fil des pages on suit, à travers de superbes images signées du photographe Vincent Moncorgé, la façon dont se fabrique cette science qui reste souvent mystérieuse. Toutes les dimensions, scientifique, esthétique et poétique, des mathématiques sont convoquées grâce à des regards croisés : la diversité des inspirations des chercheurs, la source de leur créativité, l'imaginaire littéraire et artistique des mathématiques, la drôle de tribu des mathématiciens. Un voyage au cœur de cette " auberge espagnole " des mathématiques, campus " à la française " accueillant des centaines de chercheurs du monde entier, devenu un lieu d'émulation et d'éc...

  3. Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, N.; Coates, P.J.; Uusitalo, T.

    2004-01-01

    on the role of p63 expression in human tumours, we used quantitative real-time RT-PCR to study individual p63 isoforms in squamous cell carcinomas of the head and neck (SCCHN). In keeping with previous reports, expression of the deltaN- and p63alpha-isoforms predominated and deltaNp63 mRNA was expressed...

  4. Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study

    Science.gov (United States)

    The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) [Lp(a)], Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examinati...

  5. Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer’s disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Poulsen, Keld; Bahl, Justyna Mc; Simonsen, Anja H

    2014-01-01

    BACKGROUND: Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such...

  6. MicroRNA-281 regulates the expression of ecdysone receptor (EcR) isoform B in the silkworm, Bombyx mori

    Science.gov (United States)

    Hundreds of Bombyx mori miRNAs had been identified in recent years, but their function in vivo remains poorly understood. The silkworm EcR gene (BmEcR) has three transcriptional isoforms, A, B1 and B2. Isoform sequences are different in the 3’UTR region of the gene, which is the case only in insects...

  7. Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells

    International Nuclear Information System (INIS)

    Turck, Natacha; Gross, Isabelle; Gendry, Patrick; Stutzmann, Jeanne; Freund, Jean-Noel; Kedinger, Michele; Simon-Assmann, Patricia; Launay, Jean-Francois

    2005-01-01

    Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear. Here, we report the first systematic analysis of the cellular functions of the four isoforms using the human colon adenocarcinoma Caco2/TC7 cell line as a model. We compared the respective abilities of each isoform to modulate adhesion, proliferation and differentiation of intestinal epithelial cells. We found that the isoforms were functionally distinct, with laminin-10 being the most adhesive substratum, laminin-2, laminin-5 and laminin-10 enhancing cellular proliferation and at the opposite, laminin-1 stimulating intestinal cell differentiation. To begin to characterise the molecular events induced by the different isoforms, we examined by immunofluorescence the intracellular distribution of several nuclear proteins, recently highlighted by a nuclear proteomic approach. We observed clear nucleocytoplasmic redistribution of these proteins, which depended on the laminin isoform. These results provide evidence for a distinct functional role of laminins in intestinal cell functions characterised by specific localisation of nuclear proteins

  8. Etude des erreurs d'estimation des populations par la méthode des captures successives (DeLURY, 2 captures et des captures-recaptures (PETERSEN

    Directory of Open Access Journals (Sweden)

    LAURENT M.

    1978-01-01

    Full Text Available L'estimation des populations naturelles par capture-recapture et par captures successives est souvent entachée d'erreur car, dans de nombreux cas, l'hypothèse fondamentale d'égalité des probabilités de captures pour tous les individus dans le temps et dans l'espace n'est pas respectée. Dans le cas des populations de poissons envisagés ici, les captures ont lieu par la pêche électrique. On a pu chiffrer l'ordre de grandeur des erreurs systématiques faites sur l'estimation des peuplements, en fonction des conditions particulières, biotiques et abiotiques, des différents milieux inventoriés.

  9. Reduction des effectifs ou licenciements

    CERN Multimedia

    Maiani, Luciano

    2002-01-01

    "Vous faites un amalgame entre la reduction en cours des effectifs du CERN (organisation europeenne pour la recherche nucleaire) et les economies que le laboratoire doit realiser dans les cinq ans a venir pour financer le projet de grand collisionneur de hadrons (Le Monde du 4 septembre)" (1/2 page).

  10. Les parcs des porcelainiers Haviland

    Directory of Open Access Journals (Sweden)

    Colette Chabrely

    2012-04-01

    Full Text Available Les parcs du Reynou et de Mont-Méry en Limousin, anciennes propriétés des porcelainiers Haviland, présentent l’un et l’autre un grand intérêt paysager et botanique. Dans les deux cas, l’attribution de la création est incertaine. Cet article propose pour le Reynou une analyse de documents figurés anciens permettant de préciser la chronologie des travaux du château et du parc. Pour Mont-Méry il s’agit de poser de nouveaux jalons pour une étude plus approfondie des sources et de la composition des jardins afin d’envisager de nouvelles pistes pour leur attribution.The Reynou and Mont-Méry parks near Limoges originally belonged to the city’s porcelain manufacturers, the Havilands. Both parks are of considerable interest in terms of their landscaping and their botany. In both cases, there is some uncertainty as to the identity of their designers. This article offers an analysis of the graphic representations of the Reynou park, clarifying the chronology of the creation of the château and its park. For the Mont-Méry park, the aim is to offer some guidelines for further research in the source material and on the design of the park itself, perhaps allowing for the designer to be identified.

  11. Bangalore, ville des nouvelles technologies

    Directory of Open Access Journals (Sweden)

    Clarisse Didelon

    2003-06-01

    Full Text Available Bangalore est devenue la Silicon Valley de l’Inde. Une partie de ses habitants y vit à l’occidentale mais le reste de la population souffre de la croissance spectaculaire de la ville. Face à l’insuffisance des infrastructures, Bangalore devient de moins en moins attractive pour les entreprises internationales.

  12. SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

    International Nuclear Information System (INIS)

    Short, Stephen; Malartre, Marianne; Sharpe, Colin

    2005-01-01

    SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

  13. The characterization of soybean oil body integral oleosin isoforms and the effects of alkaline pH on them.

    Science.gov (United States)

    Cao, Yanyun; Zhao, Luping; Ying, Yusang; Kong, Xiangzhen; Hua, Yufei; Chen, Yeming

    2015-06-15

    Oil body, an organelle in seed cell (naturally pre-emulsified oil), has great potentials to be used in food, cosmetics, pharmaceutical and other applications requiring stable oil-in-water emulsions. Researchers have tried to extract oil body by alkaline buffers, which are beneficial for removing contaminated proteins. But it is not clear whether alkaline buffers could remove oil body integral proteins (mainly oleosins), which could keep oil body integrity and stability. In this study, seven oleosin isoforms were identified for soybean oil body (three isoforms, 24 kDa; three isoforms, 18 kDa; one isoform, 16kDa). Oleosins were not glycoproteins and 24 kDa oleosin isoforms possessed less thiol groups than 18 kDa ones. It was found that alkaline pH not only removed contaminated proteins but also oleosins, and more and more oleosins were removed with increasing alkaline pH. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Évaluation de la valeur nutritive et recherche des substances ...

    African Journals Online (AJOL)

    SARAH

    30 juin 2016 ... et des lipides. Puis, l'évaluation a été effectuée sur ces échantillons pour rechercher la présence des alcaloïdes, des saponines, des quinones, des stéroïdes, des terpenoïdes, des flavonoïdes, des leucoanthocyanes, des tannoïdes et des hétérosides cyanogénétiques. Les teneurs moyennes en humidité ...

  15. Comparison of inhibition capability of scutellarein and scutellarin towards important liver UDP-glucuronosyltransferase (UGT) isoforms.

    Science.gov (United States)

    Ma, Guang-You; Cao, Yun-Feng; Hu, Cui-Min; Fang, Zhong-Ze; Sun, Xiao-Yu; Hong, Mo; Zhu, Zhi-Tu

    2014-03-01

    Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 μM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation

    Directory of Open Access Journals (Sweden)

    Provvidenza Maria Abruzzo

    2013-01-01

    Full Text Available Friedreich’s ataxia (FRDA is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms (FXN-1, FXN-2, and FXN-3 in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex, and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor-γ (PPARG, PPARG expression was evaluated. At a low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms and that they may have a functional role.

  17. HPLC separation of human serum albumin isoforms based on their isoelectric points

    Science.gov (United States)

    Bonilla, Lucía; Torres, María José; Schopfer, Francisco; Freeman, Bruce A.; Armas, Larissa; Ricciardi, Alejandro; Alvarez, Beatriz; Radi, Rafael

    2014-01-01

    Human serum albumin (HSA) is the most abundant protein in plasma. Cys34, the only free Cys residue, is the predominant plasma thiol and a relevant sacrificial antioxidant. Both in vivo circulating HSA and pharmaceutical preparations are heterogeneous with respect to the oxidation state of Cys34. In this work, we developed an external pH gradient chromatofocusing procedure that allows the analysis of the oxidation status of HSA in human plasma and biopharmaceutical products based on the different apparent isoelectric points and chemical properties of the redox isoforms. Specifically, reduced-mercury blocked HSA (HSA–SHg+), HSA with Cys34 oxidized to sulfenic acid (HSA–SOH) and HSA oxidized to sulfinate anion (HSA–SO2−) can be separated with resolutions of 1.4 and 3.1 (first and last pair) and hence quantified and purified. In addition, an N-terminally degraded isoform (HSA3–585) in different redox states can be resolved as well. Confirmation of the identity of the chromatofocusing isolated isoforms was achieved by high resolution whole protein MS. It is proposed that the chromatofocusing procedure can be used to produce more exact and complete descriptions of the redox status of HSA in vivo and in vitro. Finally, the scalability capabilities of the chromatofocusing procedure allow for the preparation of highly pure standards of several redox isoforms of HSA PMID:24316526

  18. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom; Venz, Simone; Junker, Heike; Kreuz, Sarah; Walther, Reinhard; Zimmermann, Uwe

    2016-01-01

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer

  19. Generating Isoform-Specific Antibodies : Lessons from Nucleocytoplasmic Glycoprotein Skp1

    NARCIS (Netherlands)

    West, Christopher M.; Van Der Wel, Hanke; Chinoy, Zoiesha; Boons, Geert Jan; Gauthier, Ted J.; Taylor, Carol M.; Xu, Yuechi

    2015-01-01

    Antibodies that discriminate protein isoforms differing by modifications at specific amino acids have revolutionized studies of their functions. Skp1 is a novel nucleocytoplasmic glycoprotein that is hydroxylated at proline-143 and then O-glycosylated by a pentasaccharide attached via a GlcNAcα1,

  20. Muscle-Type Specific Autophosphorylation of CaMKII Isoforms after Paced Contractions

    NARCIS (Netherlands)

    Eilers, W.; Gevers, W.; van Overbeek, D.; de Haan, A.; Jaspers, R.T.; Hilbers, P.A.; van Riel, A.C.R.; Flueck, M.

    2014-01-01

    We explored to what extent isoforms of the regulator of excitation-contraction and excitation-transcription coupling, calcium/calmodulin protein kinase II (CaMKII) contribute to the specificity of myocellular calcium sensing between muscle types and whether concentration transients in its

  1. Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain

    DEFF Research Database (Denmark)

    Naik, M U; Benedikz, Eirikur; Hernandez, I

    2000-01-01

    Protein kinase C (PKC) is a multigene family of at least ten isoforms, nine of which are expressed in brain (alpha, betaI, betaII, gamma, delta, straightepsilon, eta, zeta, iota/lambda). Our previous studies have shown that many of these PKCs participate in synaptic plasticity in the CA1 region...

  2. Differential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms

    DEFF Research Database (Denmark)

    Ross, Fiona A; Jensen, Thomas Elbenhardt; Hardie, D Grahame

    2016-01-01

    The g subunits of heterotrimeric AMPK complexes contain the binding sites for the regulatory adenine nucleotides AMP, ADP and ATP. We addressed whether complexes containing different g isoforms display different responses to adenine nucleotides by generating cells stably expressing FLAG-tagged ve...

  3. Biochemical Characteristics of Three Laccase Isoforms from the Basidiomycete Pleurotus nebrodensis

    Directory of Open Access Journals (Sweden)

    Xianghe Yuan

    2016-02-01

    Full Text Available The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified laccases were estimated to be 68, 64 and 51 kDa, respectively. The isoenzymes demonstrated the same optimum pH at 3.0 but slightly different temperature optima: 50–60 °C for Lac1 and Lac3 and 60 °C for Lac2. Lac2 was always more stable than the other two isoforms and exposure to 50 °C for 120 min caused 30% loss in activity. Lac2 was relatively less stable than the other two isoforms when exposed to the pH range of 3.0–8.0 for 24 h, but inactivation only occurred initially, with around 70% residual activity being maintained during the whole process. Oxidative ability towards aromatic compounds varied substantially among the isoforms and each of them displayed preference toward some substrates. Kinetic constants (Km, Kcat were determined by using a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS assay, with Lac3 showing the best affinity and Lac2 displaying the highest catalytic efficiency. Amino acid sequences from peptides derived from digestion of isoenzymes showed great consistency with laccases in the databases.

  4. Quarternary structure and enzymological properties of the different hormone-sensitive lipase (HSL) isoforms

    DEFF Research Database (Denmark)

    Krintel, Christian; Klint, Cecilia; Lindvall, Håkan

    2010-01-01

    Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of energy in the form of fatty acids from intracellular stores of neutral lipids. The enzyme has been shown to exist in different isoforms with different molecular masses (84 kDa, 89 kDa and 117 kDa) expressed in a tissue-dependen...

  5. Role of the AMPKgamma3 isoform in hypoxia-stimulated glucose transport in glycolytic skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul S; Glund, Stephan; Tom, Robby Z

    2009-01-01

    , phosphorylation of CaMKII, AMPK, ACC, and TBC1D1/D4 as well as isoform-specific AMPK activity was determined. Basal and hypoxia-mediated phosphorylation of CaMKII, AMPK, and ACC as well as alpha1- and alpha2-associated AMPK activity was comparable between AMPKgamma3-KO and wild-type mice. KN-93 reduced hypoxia...

  6. Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase

    International Nuclear Information System (INIS)

    Brizio, Carmen; Galluccio, Michele; Wait, Robin; Torchetti, Enza Maria; Bafunno, Valeria; Accardi, Rosita; Gianazza, Elisabetta; Indiveri, Cesare; Barile, Maria

    2006-01-01

    FAD synthetase (FADS) (EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor FAD. Two hypothetical human FADSs, which are the products of FLAD1 gene, were over-expressed in Escherichia coli and identified by ESI-MS/MS. Isoform 1 was over-expressed as a T7-tagged protein which had a molecular mass of 63 kDa on SDS-PAGE. Isoform 2 was over-expressed as a 6-His-tagged fusion protein, carrying an extra 84 amino acids at the N-terminal with an apparent molecular mass of 60 kDa on SDS-PAGE. It was purified near to homogeneity from the soluble cell fraction by one-step affinity chromatography. Both isoforms possessed FADS activity and had a strict requirement for MgCl 2 , as demonstrated using both spectrophotometric and chromatographic methods. The purified recombinant isoform 2 showed a specific activity of 6.8 ± 1.3 nmol of FAD synthesized/min/mg protein and exhibited a K M value for FMN of 1.5 ± 0.3 μM. This is First report on characterization of human FADS, and First cloning and over-expression of FADS from an organism higher than yeast

  7. TGF-β's delay skeletal muscle progenitor cell differentiation in an isoform-independent manner

    International Nuclear Information System (INIS)

    Schabort, Elske J.; Merwe, Mathilde van der; Loos, Benjamin; Moore, Frances P.; Niesler, Carola U.

    2009-01-01

    Satellite cells are a quiescent heterogenous population of mononuclear stem and progenitor cells which, once activated, differentiate into myotubes and facilitate skeletal muscle repair or growth. The Transforming Growth Factor-β (TGF-β) superfamily members are elevated post-injury and their importance in the regulation of myogenesis and wound healing has been demonstrated both in vitro and in vivo. Most studies suggest a negative role for TGF-β on satellite cell differentiation. However, none have compared the effect of these three isoforms on myogenesis in vitro. This is despite known isoform-specific effects of TGF-β1, -β2 and -β3 on wound repair in other tissues. In the current study we compared the effect of TGF-β1, -β2 and -β3 on proliferation and differentiation of the C2C12 myoblast cell-line. We found that, irrespective of the isoform, TGF-β increased proliferation of C2C12 cells by changing the cellular localisation of PCNA to promote cell division and prevent cell cycle exit. Concomitantly, TGF-β1, -β2 and -β3 delayed myogenic commitment by increasing MyoD degradation and decreasing myogenin expression. Terminal differentiation, as measured by a decrease in myosin heavy chain (MHC) expression, was also delayed. These results demonstrate that TGF-β promotes proliferation and delays differentiation of C2C12 myoblasts in an isoform-independent manner

  8. Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles.

    Science.gov (United States)

    Thoresen, Todd; Lenz, Martin; Gardel, Margaret L

    2013-02-05

    Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Neuronal Glucose Transporter Isoform 3 Deficient Mice Demonstrate Features of Autism Spectrum Disorders

    OpenAIRE

    Zhao, Yuanzi; Fung, Camille; Shin, Don; Shin, Bo-Chul; Thamotharan, Shanthie; Sankar, Raman; Ehninger, Dan; Silva, Alcino; Devaskar, Sherin U.

    2009-01-01

    Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristic...

  10. Alternative NF-κB Isoforms in the Drosophila Neuromuscular Junction and Brain.

    Directory of Open Access Journals (Sweden)

    Bo Zhou

    Full Text Available The Drosophila NF-κB protein Dorsal is expressed at the larval neuromuscular junction, where its expression appears unrelated to known Dorsal functions in embryonic patterning and innate immunity. Using confocal microscopy with domain-specific antisera, we demonstrate that larval muscle expresses only the B isoform of Dorsal, which arises by intron retention. We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear translocation. We further find that the Dorsal-related immune factor Dif encodes a B isoform, reflecting a conservation of B domains across a range of insect NF-κB proteins. Carrying out mutagenesis of the Dif locus via a site-specific recombineering approach, we demonstrate that Dif B is the major, if not sole, Dif isoform in the mushroom bodies of the larval brain. The Dorsal and Dif B isoforms thus share a specific association with nervous system tissues as well as an alternative protein structure.

  11. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man

    NARCIS (Netherlands)

    Bosma, P. J.; Seppen, J.; Goldhoorn, B.; Bakker, C.; Oude Elferink, R. P.; Chowdhury, J. R.; Chowdhury, N. R.; Jansen, P. L.

    1994-01-01

    Crigler-Najjar syndrome type I (CN-I) is caused by an inherited absence of UDP-glucuronosyltransferase activity toward bilirubin (B-UGT), resulting in severe non-hemolytic unconjugated hyperbilirubinemia. Based on the expression of cDNAs in COS cells, two UGT isoforms in human liver, B-UGT1 and

  12. Identification of a novel CoA synthase isoform, which is primarily expressed in Brain

    International Nuclear Information System (INIS)

    Nemazanyy, Ivan; Panasyuk, Ganna; Breus, Oksana; Zhyvoloup, Alexander; Filonenko, Valeriy; Gout, Ivan T.

    2006-01-01

    CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in Brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in Brain, requires further elucidation

  13. The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.

    Science.gov (United States)

    Obis, Teresa; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Priego, Mercedes; Simon, Anna; Garcia, Neus; Santafe, Manel M; Lanuza, Maria A; Tomàs, Josep

    2015-12-01

    Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.

  14. The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

    DEFF Research Database (Denmark)

    Liu, Daren; Trojanowicz, Bogusz; Ye, Longyun

    2012-01-01

    CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data ...

  15. Roles of SGK Isoform Signaling in Breast Cancer Migration and Invasion

    Science.gov (United States)

    2011-04-01

    significant number of overlapping substrates, and deregulation in breast carcinoma (5,6). To date, no studies have investigated any role for SGK in cell...isoforms in breast carcinoma cell lines (months 2-3) To insure specificity of SGK knockdown in breast cancer cell lines I made two different specific

  16. The activity and isoforms of NADP-malic enzyme in Nicotiana benthamiana plants under biotic stress

    Czech Academy of Sciences Publication Activity Database

    Doubnerová, V.; Jirásková, A.; Janošková, M.; Müller, Karel; Baťková, Petra; Synková, Helena; Čeřovská, Noemi; Ryšlavá, H.

    2007-01-01

    Roč. 26, č. 4 (2007), s. 281-289 ISSN 0231-5882 Institutional research plan: CEZ:AV0Z50380511 Keywords : NADP * malic enzyme isoforms * Nicotiana benthamiana Subject RIV: EF - Botanics Impact factor: 1.286, year: 2007 http://www.gpb.sav.sk/2007-4.htm

  17. Opioid precursor protein isoform is targeted to the cell nuclei in the human brain

    DEFF Research Database (Denmark)

    Kononenko, Olga; Bazov, Igor; Watanabe, Hiroyuki

    2017-01-01

    to the cell nuclei in a model cellular system. This may be driven by bipartite nuclear localization signal (NLS) that is cryptic in the full-length PDYN molecule and becomes functional when signal peptide is truncated. Nuclear PDYN isoform was identified by western blot and radioimmunoassay in neuronal nuclei...

  18. Cryptocephal, the Drosophila melanogaster ATF4, is a specific coactivator for ecdysone receptor isoform B2.

    Directory of Open Access Journals (Sweden)

    Sebastien A Gauthier

    Full Text Available The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR and Ultraspiracle (USP. In Drosophila melanogaster, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4 is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC, the Drosophila homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH, an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.

  19. A novel MCPH1 isoform complements the defective chromosome condensation of human MCPH1-deficient cells.

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    Ioannis Gavvovidis

    Full Text Available Biallelic mutations in MCPH1 cause primary microcephaly (MCPH with the cellular phenotype of defective chromosome condensation. MCPH1 encodes a multifunctional protein that notably is involved in brain development, regulation of chromosome condensation, and DNA damage response. In the present studies, we detected that MCPH1 encodes several distinct transcripts, including two major forms: full-length MCPH1 (MCPH1-FL and a second transcript lacking the six 3' exons (MCPH1Δe9-14. Both variants show comparable tissue-specific expression patterns, demonstrate nuclear localization that is mediated independently via separate NLS motifs, and are more abundant in certain fetal than adult organs. In addition, the expression of either isoform complements the chromosome condensation defect found in genetically MCPH1-deficient or MCPH1 siRNA-depleted cells, demonstrating a redundancy of both MCPH1 isoforms for the regulation of chromosome condensation. Strikingly however, both transcripts are regulated antagonistically during cell-cycle progression and there are functional differences between the isoforms with regard to the DNA damage response; MCPH1-FL localizes to phosphorylated H2AX repair foci following ionizing irradiation, while MCPH1Δe9-14 was evenly distributed in the nucleus. In summary, our results demonstrate here that MCPH1 encodes different isoforms that are differentially regulated at the transcript level and have different functions at the protein level.

  20. Osteoporose und Genetik des Knochenstoffwechsels

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B

    2002-01-01

    Full Text Available Osteoporose ist in hohem Maß genetisch determiniert. Neue Wege der molekularbiologischen Forschung haben sich in den letzten Jahren auf diesem Gebiet etabliert. "Gene mapping" mit polymorphen genetischen Markern auf der Suche nach Phänotyp-assoziierten Genen ist ein aufwendiges, aber vielversprechendes Verfahren und wird durch die Erkenntnisse des Human Genome Projects beschleunigt. So wurde jüngst u. a. das Low-density Lipoprotein 5-Gen als wichtig für den Knochenstoffwechsel identifiziert. Kandidaten-gene wie Hormonrezeptor-, Cytokin- oder Kollagen-Gene werden hinsichtlich ihrer Gen-Gen- und Gen-Umwelt- Interaktionen untersucht und erlauben neue funktionelle Einsichten in Erkrankungen des Knochenstoffwechsels. Mutationen der Kollagen-Gene sind bei einigen seltenen Erkrankungen, wie dem Osteoporose-Pseudogliom-Syndrom oder der Osteogenesis imperfecta gefunden worden, könnten aber auch für häufige Varianten von Bindegewebsstörungen wie der congenitalen Hüftdysplasie verantwortlich sein, die etwa 10 % der weiblichen kaukasischen Bevölkerung in unterschiedlichem Ausmaß betrifft. Osteoporose am Schenkelhals und erhöhte Gelenkslaxizität sowie andere generalisierte Veränderungen des Knochen- und Kollagenstoffwechsels können hier möglicherweise ebenfalls durch Störungen des Kollagen I alpha 1-Gens erklärt werden. In Summe können wir zahlreiche neue Einsichten in die Pathophysiologie des Skelettsystems erwarten, die uns auch neue Zugangswege für Diagnostik und Therapie unserer Patienten ermöglichen werden.

  1. L'astronomie des Anciens

    Science.gov (United States)

    Nazé, Yaël

    2009-04-01

    Quelle que soit la civilisation à laquelle il appartient, l'être humain cherche dans le ciel des réponses aux questions qu'il se pose sur son origine, son avenir et sa finalité. Le premier mérite de ce livre est de nous rappeler que l'astronomie a commencé ainsi à travers les mythes célestes imaginés par les Anciens pour expliquer l'ordre du monde et la place qu'ils y occupaient. Mais les savoirs astronomiques passés étaient loin d'être négligeables et certainement pas limités aux seuls travaux des Grecs : c'est ce que l'auteur montre à travers une passionnante enquête, de Stonehenge à Gizeh en passant par Pékin et Mexico, fondée sur l'étude des monuments anciens et des sources écrites encore accessibles. Les tablettes mésopotamiennes, les annales chinoises, les chroniques médiévales, etc. sont en outre d'une singulière utilité pour les astronomes modernes : comment sinon remonter aux variations de la durée du jour au cours des siècles, ou percer la nature de l'explosion qui a frappé tant d'observateurs en 1054 ? Ce livre offre un voyage magnifiquement illustré à travers les âges, entre astronomie et archéologie.

  2. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  3. Kalrn promoter usage and isoform expression respond to chronic cocaine exposure

    Directory of Open Access Journals (Sweden)

    Ma Xin-Ming

    2011-02-01

    Full Text Available Abstract Background The long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs contain additional domains known to interact with phosphatidylinositides as well as with a number of different proteins. Through their activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal organization. Chronic exposure of adult male rodents to cocaine increases levels of Kalirin 7 in the striatum. When exposed chronically to cocaine, mice lacking Kalirin 7, the major adult isoform, fail to show an increase in dendritic spine density in the nucleus accumbens, show diminished place preference for cocaine, and exhibit increased locomotor activity in response to cocaine. Results The use of alternate promoters and 3'-terminal exons of the mouse Kalrn gene were investigated using real-time quantitative polymerase chain reaction. While the two most distal full-length Kalrn promoters are used equally in the prefrontal cortex, the more proximal of these promoters accounts for most of the transcripts expressed in the nucleus accumbens. The 3'-terminal exon unique to the Kalirin 7 isoform accounts for a greater percentage of the Kalrn transcripts in prefrontal cortex than in nucleus accumbens. Western blot analyses confirmed these differences. Chronic cocaine treatment increases usage of the promoter encoding the Δ-Kalirin isoforms but does not alter full-length Kalirin promoter usage. Usage of the 3'-terminal exon unique to Kalirin 7 increases following chronic cocaine exposure. Conclusions Kalrn promoter and 3'-terminal exon utilization are region-specific. In the nucleus accumbens, cocaine-mediated alterations in promoter usage and 3'-terminal exon usage favor expression of

  4. Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

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    Marina Beltrami-Moreira

    Full Text Available Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms α and β have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1α and IL-1β in the induction of MMP-3 and other matrix-remodeling enzymes in human cells.Human primary vascular smooth muscle cells (VSMCs and carotid endarterectomy specimens were stimulated with equimolar concentrations of IL-1α or IL-1β and analyzed protease expression by immunoblot and ELISA. Either IL-1α or IL-1β increased the expression of pro-MMP-3 in VSMCs, facilitated VSMC migration through Matrigel, and induced MMP-3 production in specimens from atheromatous plaques. VSMCs also secreted MMP-1 and Cathepsin S (CatS upon stimulation with IL-1α or IL-1β. IL-1 isoforms similarly increased MMP-1 and MMP-9 expression in carotid endarterectomy specimens. We examined the expression of MMP-3 and IL-1 isoforms by immunostaining of carotid atheromata, calculated the % positive areas, and tested associations by linear regression. MMP-3 colocalized with IL-1 isoforms in atheromata. MMP-3+ area in plaques positively associated with IL-1α+ (R2 = 0.61, P<0.001 and with IL-1β + areas (R2 = 0.68, P<0.001. MMP-3+ area within atheroma also associated with CD68+ area, but not with α-smooth muscle actin area.Either IL-1α or IL-1β can induce the expression of enzymes implicated in remodeling of the arterial extracellular matrix, and facilitate human VSMC migration in vitro. Human atheromata contain both IL-1 isoforms in association with immunoreactive MMP-3. This redundancy of IL-1 isoforms suggests that selective blocking of one IL-1 isoform should not impair expansive arterial remodeling, a finding with important clinical implications for therapeutic targeting of IL-1 in atherosclerosis.

  5. Two Distinct Isoforms of Matrix Metalloproteinase-2 Are Associated with Human Delayed Kidney Graft Function.

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    Shaynah Wanga

    Full Text Available Delayed graft function (DGF is a frequent complication of renal transplantation, particularly in the setting of transplantation of kidneys derived from deceased donors and expanded-criteria donors. DGF results from tubular epithelial cell injury and has immediate and long term consequences. These include requirement for post-transplantation dialysis, increased incidence of acute rejection, and poorer long-term outcomes. DGF represents one of the clearest clinical examples of renal acute ischemia/reperfusion injury. Experimental studies have demonstrated that ischemia/reperfusion injury induces the synthesis of the full length secreted isoform of matrix metalloproteinase-2 (FL-MMP-2, as well as an intracellular N-terminal truncated MMP-2 isoform (NTT-MMP-2 that initiates an innate immune response. We hypothesized that the two MMP-2 isoforms mediate tubular epithelial cell injury in DGF. Archival renal biopsy sections from 10 protocol biopsy controls and 41 cases with a clinical diagnosis of DGF were analyzed for the extent of tubular injury, expression of the FL-MMP-2 and NTT-MMP-2 isoforms by immunohistochemistry (IHC, in situ hybridization, and qPCR to determine isoform abundance. Differences in transcript abundance were related to tubular injury score. Markers of MMP-2-mediated injury included TUNEL staining and assessment of peritubular capillary density. There was a clear relationship between tubular epithelial cell expression of both FL-MMP-2 and NTT-MMP-2 IHC with the extent of tubular injury. The MMP-2 isoforms were detected in the same tubular segments and were present at sites of tubular injury. qPCR demonstrated highly significant increases in both the FL-MMP-2 and NTT-MMP-2 transcripts. Statistical analysis revealed highly significant associations between FL-MMP-2 and NTT-MMP-2 transcript abundance and the extent of tubular injury, with NTT-MMP-2 having the strongest association. We conclude that two distinct MMP-2 isoforms are

  6. Deep Sequencing Reveals Uncharted Isoform Heterogeneity of the Protein-Coding Transcriptome in Cerebral Ischemia.

    Science.gov (United States)

    Bhattarai, Sunil; Aly, Ahmed; Garcia, Kristy; Ruiz, Diandra; Pontarelli, Fabrizio; Dharap, Ashutosh

    2018-06-03

    Gene expression in cerebral ischemia has been a subject of intense investigations for several years. Studies utilizing probe-based high-throughput methodologies such as microarrays have contributed significantly to our existing knowledge but lacked the capacity to dissect the transcriptome in detail. Genome-wide RNA-sequencing (RNA-seq) enables comprehensive examinations of transcriptomes for attributes such as strandedness, alternative splicing, alternative transcription start/stop sites, and sequence composition, thus providing a very detailed account of gene expression. Leveraging this capability, we conducted an in-depth, genome-wide evaluation of the protein-coding transcriptome of the adult mouse cortex after transient focal ischemia at 6, 12, or 24 h of reperfusion using RNA-seq. We identified a total of 1007 transcripts at 6 h, 1878 transcripts at 12 h, and 1618 transcripts at 24 h of reperfusion that were significantly altered as compared to sham controls. With isoform-level resolution, we identified 23 splice variants arising from 23 genes that were novel mRNA isoforms. For a subset of genes, we detected reperfusion time-point-dependent splice isoform switching, indicating an expression and/or functional switch for these genes. Finally, for 286 genes across all three reperfusion time-points, we discovered multiple, distinct, simultaneously expressed and differentially altered isoforms per gene that were generated via alternative transcription start/stop sites. Of these, 165 isoforms derived from 109 genes were novel mRNAs. Together, our data unravel the protein-coding transcriptome of the cerebral cortex at an unprecedented depth to provide several new insights into the flexibility and complexity of stroke-related gene transcription and transcript organization.

  7. Isoform-specific proteasomal degradation of Rbfox3 during chicken embryonic development

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kee K.; Adelstein, Robert S.; Kawamoto, Sachiyo, E-mail: kawamots@mail.nih.gov

    2014-08-08

    Highlights: • Protein stability of Rbfox3 splice isoforms is differentially regulated. • Rbfox3-d31, an Rbfox3 isoform lacking the RRM, is highly susceptible to degradation. • The protein stability of Rbfox3-d31 is regulated by the ubiquitin–proteasome pathway. • Rbfox3-d31 inhibits the nuclear localization of Rbfox2. • Rbfox3-d31 inhibits the splicing activity of Rbfox2. - Abstract: Rbfox3, a neuron-specific RNA-binding protein, plays an important role in neuronal differentiation during development. An isoform Rbfox3-d31, which excludes the 93-nucleotide cassette exon within the RNA recognition motif of chicken Rbfox3, has been previously identified. However, the cellular functions of Rbfox3-d31 remain largely unknown. Here we find that Rbfox3-d31 mRNA is highly expressed during the early developmental stages of the chicken embryo, while Rbfox3-d31 protein is barely detected during the same stage due to its rapid degradation mediated by the ubiquitin–proteasome pathway. Importantly, this degradation is specific to the Rbfox3-d31 isoform and it does not occur with full-length Rbfox3. Furthermore, suppression of Rbfox3-d31 protein degradation with the proteasome inhibitor MG132 attenuates the splicing activity of another Rbfox family member Rbfox2 by altering the subcellular localization of Rbfox2. These results suggest that Rbfox3-d31 functions as a repressor for the splicing activity of the Rbfox family and its protein level is regulated in an isoform-specific manner in vivo.

  8. Myosin isoform switching during assembly of the Drosophila flight muscle thick filament lattice.

    Science.gov (United States)

    Orfanos, Zacharias; Sparrow, John C

    2013-01-01

    During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding exon inserted into the single Drosophila muscle myosin heavy chain gene, Mhc. The weeP26 IFM sarcomeres have a unique MHC-GFP-labelling pattern restricted to the sarcomere core, explained by non-translation of the GFP exon following alternative splicing. Characterisation of wild-type IFM MHC mRNA confirmed the presence of an alternately spliced isoform, expressed earlier than the major IFM-specific isoform. The two wild-type IFM-specific MHC isoforms differ by the presence of a C-terminal 'tailpiece' in the minor isoform. The sequential expression and assembly of these two MHCs into developing thick filaments suggest a role for the tailpiece in initiating A-band formation. The restriction of the MHC-GFP sarcomeric pattern in weeP26 is lifted when the IFM lack the IFM-specific myosin binding protein flightin, suggesting that it limits myosin dissociation from thick filaments. Studies of flightin binding to developing thick filaments reveal a progressive binding at the growing thick filament tips and in a retrograde direction to earlier assembled, proximal filament regions. We propose that this flightin binding restricts myosin molecule incorporation/dissociation during thick filament assembly and explains the location of the early MHC isoform pattern in the IFM A-band.

  9. Statistical modeling of isoform splicing dynamics from RNA-seq time series data.

    Science.gov (United States)

    Huang, Yuanhua; Sanguinetti, Guido

    2016-10-01

    Isoform quantification is an important goal of RNA-seq experiments, yet it remains problematic for genes with low expression or several isoforms. These difficulties may in principle be ameliorated by exploiting correlated experimental designs, such as time series or dosage response experiments. Time series RNA-seq experiments, in particular, are becoming increasingly popular, yet there are no methods that explicitly leverage the experimental design to improve isoform quantification. Here, we present DICEseq, the first isoform quantification method tailored to correlated RNA-seq experiments. DICEseq explicitly models the correlations between different RNA-seq experiments to aid the quantification of isoforms across experiments. Numerical experiments on simulated datasets show that DICEseq yields more accurate results than state-of-the-art methods, an advantage that can become considerable at low coverage levels. On real datasets, our results show that DICEseq provides substantially more reproducible and robust quantifications, increasing the correlation of estimates from replicate datasets by up to 10% on genes with low or moderate expression levels (bottom third of all genes). Furthermore, DICEseq permits to quantify the trade-off between temporal sampling of RNA and depth of sequencing, frequently an important choice when planning experiments. Our results have strong implications for the design of RNA-seq experiments, and offer a novel tool for improved analysis of such datasets. Python code is freely available at http://diceseq.sf.net G.Sanguinetti@ed.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach.

    Science.gov (United States)

    Peng, Huiming; Peng, Tao; Wen, Jianguo; Engler, David A; Matsunami, Risë K; Su, Jing; Zhang, Le; Chang, Chung-Che Jeff; Zhou, Xiaobo

    2014-07-01

    p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography-mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts.

    Directory of Open Access Journals (Sweden)

    Maléne E Lindholm

    2016-09-01

    Full Text Available Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.

  12. Enquête de satisfaction des restaurants

    CERN Multimedia

    Staff Association

    2016-01-01

    Comité de surveillance des restaurants L’Association du personnel est représentée dans plusieurs comités dont le Comité de surveillance des restaurants (CSR) qui a pour mandat : de donner son avis sur toute question relative à la politique générale de l’Organisation en matière de restauration sur le site, y compris en ce qui concerne les termes et l’attribution des contrats d’exploitation des restaurants ; de définir dans le cadre des contrats d’exploitation des restaurants, les prestations correspondant aux besoins et, dans la mesure du possible, aux désirs du personnel ; de surveiller les prestations des restaurants, y compris en ce qui concerne la qualité et la préparation des produits ; de négocier avec les concessionnaires des restaurants au sujet des tarifs et de surveill...

  13. Administration et gestion des contrats XL

    CERN Document Server

    Senouf, J

    2000-01-01

    Les grands contrats de travaux génèrent un grand nombre de commandes (OSVC) passées par un grand nombre de responsables techniques. Ils sont généralement basés sur des bordereaux de prix associés à un éventail de conditions économiques adaptées aux besoins complexes et variés des multiples utilisateurs du CERN nécessitant des calculs sophistiqués. L'administration des commandes, le suivi des travaux et de la facturation doivent répondre aux besoins de tous les acteurs. Les responsables techniques doivent jouir de la plus large indépendance administrative dans le respect des règlements CERN et des conditions contractuelles. Le contrôle des métrés et décomptes doit être rigoureux et d'une traçabilité complète. L'utilisation des bases de données Oracle a déjà permis l'intégration des données administratives et techniques. Le Web nous invite à une communication totale et transparente entre les utilisateurs, les services techniques et les contractants. De nouveaux types de contrat so...

  14. La production mondiale des vins

    Directory of Open Access Journals (Sweden)

    Pierre GALET

    1970-06-01

    On sait peu de choses précises sur l'origine de la culture de la vigne en Gaule. Il est probable qu'il existait des lambrusques sauvages dans les forêts et les sous-bois dont les habitants récoltaient les raisins pour les consommer à l'état frais et peut-être en tiraient-ils aussi une boisson fermentée comme ils le faisaient pour l'orge ou pour le miel (hydromel. Il est vraisemblable aussi que les navigateurs phocéens, venus commercer sur les rivages de la Méditerranée, apportèrent du vin aux gaulois, leur apprirent à tailler la vigne et finalement, en établissant des comptoirs, amenèrent des boutures de vignes de leur propre pays. On sait que les gaulois apprécièrent très vite le vin et ce fut une des raisons de leurs invasion de la Toscane pour y consommer sur place cette « boisson magique ». Plus tard avec l'occupation romaine la culture de la vigne s'étendit dans toute la province narbonnaise, dans la vallée du Rhône jusqu'aux portes de Lyon, puis en Aquitaine. A leur tour les romains se mirent à apprécier les vins gaulois, de qualité supérieure à ceux récoltés en Italie sur les Hautains. A l'aide de la navigation fluviale sur le Rhône les vins gagnèrent Rome, ainsi que ceux embarqués dans les petits ports du rivage méditerranéen. Puis au cours des siècles et grâce notamment aux religieux catholiques la vigne se répandit dans toutes les provinces. A la veille de la Révolution, en 1788, on estimait la superficie cultivée à 1.567.000 hectares, produisant 27 millions d'hectolitres. Au cours du XIXe siècle, les plantations augmentèrent en raison des facilités de transport que permettait l'établissement des lignes de chemin de fer. Le ravitaillement des grandes villes fut assuré par la création d'un important vignoble dans le Midi. En 1875, la superficie cultivée dépassait 2,4 millions d'hectares et la France produisit 83,8 millions d'hectolitres, record absolu qui ne fut jamais plus atteint depuis. La crise phyllox

  15. La territorialisation des politiques environnementales

    Directory of Open Access Journals (Sweden)

    Amédée Mollard

    2010-10-01

    Full Text Available Le point de départ de cet article est la grande variabilité de la pollution nitrique diffuse de l’eau due à l’agriculture. Celle-ci dépend en particulier du climat, des types de sol et des systèmes de production agricole. Nos recherches réalisées de façon interdisciplinaire à partir de deux sites différents en France, montrent que cette hétérogénéité spatio-temporelle conditionne les pratiques agricoles mises en œuvre pour réduire la pollution au niveau de la norme admise. De ce fait, les pratiques les plus « coût-efficaces » diffèrent d’un territoire à l’autre, en fonction des caractéristiques locales. Ces résultats mettent donc en évidence une efficacité potentielle d’une territorialisation des politiques publiques. En théorie, de telles politiques sont considérées comme optimales par les économistes, car elles incitent les agents à moduler leurs efforts en fonction de la sensibilité du milieu. Mais, selon les études empiriques, cet avantage serait annulé par un coût élevé de mise en œuvre, de contrôle et de surveillance. Pour maintenir leur avantage sur des politiques uniformes, les politiques territorialisées devraient être mises en œuvre à un niveau spatial optimal. Un tel niveau devrait au minimum atteindre un compromis entre l’économie réalisée grâce à une modulation adaptée aux conditions locales et les sur-coûts dus à la décentralisation des solutions mises en œuvre. Cet article analyse la pertinence d’une prise en compte de ces spécificités par des politiques territorialisées. L’efficacité d’une régulation différenciée de la pollution nitrique est étudiée ici en évaluant l’importance de la variabilité spatiale des paramètres physiques et des coûts de la territorialisation.The paper starts with the wide variability of nonpoint water nitrogenous pollution generated by agriculture. This variability depends especially on climate, soil types and farming

  16. DMPD: The role of C/EBP isoforms in the control of inflammatory and native immunityfunctions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9792624 The role of C/EBP isoforms in the control of inflammatory and native immunityfunction...f C/EBP isoforms in the control of inflammatory and native immunityfunctions. PubmedID 9792624 Title The rol...e of C/EBP isoforms in the control of inflammatory and native immunityfunctions.

  17. DES EFFETS DURABLES DES VIES TRANSFORMÉES

    International Development Research Centre (IDRC) Digital Library (Canada)

    Son but est simple : veiller à ce que les personnes les plus vulnérables dans le monde, en particulier ... Simple et pourtant très efficace, le filtre biosable fournit de l'eau potable dans plus de 300 000 foyers de par le ... de rétablir la fertilité des sols dégradés par l'extraction de l'argile nécessaire à la fabrication de briques, ...

  18. Regroupement des statistiques sur le secteur des TIC et analyse ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La présence et l'influence des technologies de l'information et de la communication (TIC) continuent de s'élargir et de s'accroître, tout comme leurs répercussions sur le développement économique. Toutefois, il reste encore beaucoup de travail à faire avant de pouvoir comprendre d'une manière systématique et ...

  19. Étude cytogenetique des aberrations chromosomiques chez des ...

    African Journals Online (AJOL)

    Ces techniciens et volontaires témoins ont été soumis à l'épreuve de prélèvement de 5 ml de sang veineux au pli du coude dans des tubes d'héparine sodique. Après 48 ... These technicians and Volunteers (controls) were subjected to the test sample of 5 ml of venous blood to the elbow crease in sodium heparin tubes.

  20. Des experts discutent des conflits non conventionnels dans les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    21 juil. 2015 ... Le rapport souligne les principaux défis à relever lorsqu'il est question de conflits non conventionnels et de violence dans les Amériques. ... Bien que de nombreux États aient recours à la médiation avec des acteurs du crime organisé en vue de réduire le nombre de leurs actes de violence ou d'y mettre fin, ...

  1. Effets des biomasses vertes de Tithonia diversifolia et des engrais ...

    African Journals Online (AJOL)

    même dans les sols peu fertiles (McKey et al.,. 2012 ; Temegne et al., 2015). Cependant, il peut aussi produire beaucoup plus lorsqu'il est cultivé avec un supplément judicieux d'engrais. La fertilisation minérale conventionnelle est incompatible avec le contexte économique du paysan camerounais du fait du coût élevé des ...

  2. Crystallization and Identification of the Glycosylated Moieties of Two Isoforms of the Main Allergen Hev b 2 and Preliminary X-ray Analysis of Two Polymorphs of Isoform ll

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes-Silva,D.; Mendoza-Hernandez, G.; Stojanoff, V.; Palomares, L.; Zenteno, E.; Torres-Larios, A.; Rodriguez-Romero, A.

    2007-01-01

    Latex from Hevea brasiliensis contains several allergenic proteins that are involved in type I allergy. One of them is Hev b 2, which is a {beta}-1,3-glucanase enzyme that exists in different isoforms with variable glycosylation content. Two glucanase isoforms were isolated from trees of the GV-42 clone by gel filtration, affinity and ion-exchange chromatography. Isoform I had a carbohydrate content of about 20%, with N-linked N-acetyl-glucosamine, N-acetyl-galactosamine, fucose and galactose residues as the main sugars, while isoform II showed 6% carbohydrate content consisting of N-acetyl-glucosamine, fucose, mannose and xylose. Both isoforms were crystallized by the hanging-drop vapor-diffusion method. Isoform I crystals were grown using 0.2 M trisodium citrate dihydrate, 0.1 M Na HEPES pH 7.5 and 20%(v/v) 2-propanol, but these crystals were not appropriate for data collection. Isoform II crystals were obtained under two conditions and X-ray diffraction data were collected from both. In the first condition (0.2 M trisodium citrate, 0.1 M sodium cacodylate pH 6.5, 30% 2-propanol), crystals belonging to the tetragonal space group P4{sub 1} with unit-cell parameters a = b = 150.17, c = 77.41 {angstrom} were obtained. In the second condition [0.2 M ammonium acetate, 0.1 M trisodium citrate dihydrate pH 5.6, 30%(w/v) polyethylene glycol 4000] the isoform II crystals belonged to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 85.08, b = 89.67, c = 101.80 {angstrom}, {beta}= 113.6{sup o}. Preliminary analysis suggests that there are four molecules of isoform II in both asymmetric units.

  3. Crystallization and identification of the glycosylated moieties of two isoforms of the main allergen Hev b 2 and preliminary X-ray analysis of two polymorphs of isoform II

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes-Silva, D. [Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico); Mendoza-Hernández, G. [Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico); Stojanoff, V. [Brookhaven National Laboratory, National Synchrotron Light Source, Upton, NY (United States); Palomares, L. A. [Instituto de Biotecnología, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico); Zenteno, E. [Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico); Torres-Larios, A. [Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico); Rodríguez-Romero, A., E-mail: adela@servidor.unam.mx [Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Cuidad Universitaria, Coyoacán, México, DF 04510 (Mexico)

    2007-09-01

    Crystallization of important glycoenzymes involved in IgE-mediated latex allergy. Latex from Hevea brasiliensis contains several allergenic proteins that are involved in type I allergy. One of them is Hev b 2, which is a β-1,3-glucanase enzyme that exists in different isoforms with variable glycosylation content. Two glucanase isoforms were isolated from trees of the GV-42 clone by gel filtration, affinity and ion-exchange chromatography. Isoform I had a carbohydrate content of about 20%, with N-linked N-acetyl-glucosamine, N-acetyl-galactosamine, fucose and galactose residues as the main sugars, while isoform II showed 6% carbohydrate content constisting of N-acetyl-glucosamine, fucose, mannose and xylose. Both isoforms were crystallized by the hanging-drop vapour-diffusion method. Isoform I crystals were grown using 0.2 M trisodium citrate dihydrate, 0.1 M Na HEPES pH 7.5 and 20%(v/v) 2-propanol, but these crystals were not appropriate for data collection. Isoform II crystals were obtained under two conditions and X-ray diffraction data were collected from both. In the first condition (0.2 M trisodium citrate, 0.1 M sodium cacodylate pH 6.5, 30% 2-propanol), crystals belonging to the tetragonal space group P4{sub 1} with unit-cell parameters a = b = 150.17, c = 77.41 Å were obtained. In the second condition [0.2 M ammonium acetate, 0.1 M trisodium citrate dihydrate pH 5.6, 30%(w/v) polyethylene glycol 4000] the isoform II crystals belonged to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 85.08, b = 89.67, c = 101.80 Å, β = 113.6°. Preliminary analysis suggests that there are four molecules of isoform II in both asymmetric units.

  4. Crystallization and identification of the glycosylated moieties of two isoforms of the main allergen Hev b 2 and preliminary X-ray analysis of two polymorphs of isoform II

    International Nuclear Information System (INIS)

    Fuentes-Silva, D.; Mendoza-Hernández, G.; Stojanoff, V.; Palomares, L. A.; Zenteno, E.; Torres-Larios, A.; Rodríguez-Romero, A.

    2007-01-01

    Crystallization of important glycoenzymes involved in IgE-mediated latex allergy. Latex from Hevea brasiliensis contains several allergenic proteins that are involved in type I allergy. One of them is Hev b 2, which is a β-1,3-glucanase enzyme that exists in different isoforms with variable glycosylation content. Two glucanase isoforms were isolated from trees of the GV-42 clone by gel filtration, affinity and ion-exchange chromatography. Isoform I had a carbohydrate content of about 20%, with N-linked N-acetyl-glucosamine, N-acetyl-galactosamine, fucose and galactose residues as the main sugars, while isoform II showed 6% carbohydrate content constisting of N-acetyl-glucosamine, fucose, mannose and xylose. Both isoforms were crystallized by the hanging-drop vapour-diffusion method. Isoform I crystals were grown using 0.2 M trisodium citrate dihydrate, 0.1 M Na HEPES pH 7.5 and 20%(v/v) 2-propanol, but these crystals were not appropriate for data collection. Isoform II crystals were obtained under two conditions and X-ray diffraction data were collected from both. In the first condition (0.2 M trisodium citrate, 0.1 M sodium cacodylate pH 6.5, 30% 2-propanol), crystals belonging to the tetragonal space group P4 1 with unit-cell parameters a = b = 150.17, c = 77.41 Å were obtained. In the second condition [0.2 M ammonium acetate, 0.1 M trisodium citrate dihydrate pH 5.6, 30%(w/v) polyethylene glycol 4000] the isoform II crystals belonged to the monoclinic space group P2 1 , with unit-cell parameters a = 85.08, b = 89.67, c = 101.80 Å, β = 113.6°. Preliminary analysis suggests that there are four molecules of isoform II in both asymmetric units

  5. Caractérisation des plantes médicinales à flavonoïdes des marchés ...

    African Journals Online (AJOL)

    Les espèces guinéo-congolaises sont les plus abondantes et le mode de dissémination majoritaire des diaspores est la zoochorie. Les plantes à flavonoïdes les plus utilisées sont : Combretum micranthum, Aloe vera, Ageratum conyzoïdes et Cylicodiscus gabonensis. Elles rentrent dans le traitement de 73 maladies parmi ...

  6. Utilización de redes neuronales para la determinación de respuestas de sitio a partir de Ondas coda Aplicación para Armenia Colombia

    Directory of Open Access Journals (Sweden)

    Vargas Jiménez Carlos A.

    2001-08-01

    neuronales facilitan el proceso de deducción de funciones de transferencia lineales y no lineales orientadas a la evaluación dinámica de suelos.

  7. Orientation of a 3D object: implementation with an artificial neural network using a programmable logic device;Orientacion de un objeto 3D : implementacion de redes neuronales artificiales utilizando logica programable

    Energy Technology Data Exchange (ETDEWEB)

    Carnevale, Federico J [Universidad Nacional de Cuyo, Instituto Balseiro, Centro Atomico Bariloche (Argentina)

    2010-07-01

    Complex information extraction from images is a key skill of intelligent machines, with wide application in automated systems, robotic manipulation and human-computer interaction. However, solving this problem with traditional, geometric or analytical, strategies is extremely difficult. Therefore, an approach based on learning from examples seems to be more appropriate. This thesis addresses the problem of 3D orientation, aiming to estimate the angular coordinates of a known object from an image shot from any direction. We describe a system based on artificial neural networks to solve this problem in real time. The implementation is performed using a programmable logic device. The digital system described in this paper has the ability to estimate two rotational coordinates of a 3D known object, in ranges from -80{sup 0} to 80{sup 0}. The operation speed allows a real time performance at video rate. The system accuracy can be successively increased by increasing the size of the artificial neural network and using a larger number of training examples;La extraccion de informacion compleja a partir de imagenes es una habilidad clave en las maquinas inteligentes con vasta aplicacion en los sistemas automatizados, la manipulacion robotica y la interaccion humano-computadora. Sin embargo, resulta una tarea extremadamente dificil de resolver con estrategias clasicas, geometricas o analiticas. Por lo tanto, un enfoque basado en aprendizaje a partir de ejemplos parece mas adecuado. Esta tesis trata acerca del problema de orientacion 3D, cuyo objetivo consiste en estimar las coordenadas angulares de un objeto conocido, a partir de una imagen tomada desde cualquier direccion. Se describe un sistema, basado en redes neuronales artificiales, para resolver este problema en tiempo real. La implementacion, capaz de funcionar a frecuencia de video, se realiza utilizando un dispositivo de logica programable. El sistema digital final demuestra la capacidad de estimar dos coordenadas

  8. Análisis de sistema de potencia desbalanceado con el empleo de herramientas estadísticas, coeficientes complejos y redes neuronales artificiales; Statistical, Complex Factor and Neural Networks Analysis and Simulation of an Unbalance Power Systems

    Directory of Open Access Journals (Sweden)

    Marcos A de Armas Teyra

    2011-02-01

    Full Text Available Se caracteriza estadísticamente el desbalance de tensión en un sistema eléctrico de potencia en términos de laIEEE y se señalan algunas informaciones útiles adicionales que se obtienen de esta. Se muestra cuán sostenidapuede ser la explotación de un conjunto de potentes motores asincrónicos fuera de las normas internacionaleshaciéndose énfasis en aspectos energéticos al determinar la potencia demandada y la energía adicional consumidadebido a la asimetría. Por último, se presenta una red neuronal cuya función es determinar el desbalance, emitirseñales de alarma y producir el disparo del sistema si fuese necesario. Para este propósito se utilizan no solo lastensiones de fase, sino las corrientes de línea y los coeficientes complejos de desbalance. Se concluye con queel desbalance es un problema energético que produce demandas y pérdidas que pueden ser cuantificadas por elcoeficiente de asimetría y el análisis estadístico. Las redes neuronales pueden ser entrenadas para ofreceralarma, protección y otras tareas en los sistemas eléctricos de potencia. También pueden ser incorporadas a lossistemas modernos de mediciones digitalizadas en los servicios industriales. Para la validación de los resultados,se emplean las mediciones recién efectuadas en una estación de bombeo del acueducto de la provincia deCienfuegos, Cuba.  There are tree goals in this article; statistical characterization of an unbalanced power system, show how longan asynchronous group of motors can be exploited out of international unbalance standards focused on powerdemand and energy consumption due to asymmetry complex defined factor and to present an artificial neuralnetwork used to send warning signals or to protect the motors under abnormal unbalanced conditions. As a case,a water supply station in Cienfuegos`s province is presented.sequence and the possibilities that this designpresents for the increase of the security of the installationI.

  9. Intensidad exportadora e interacción entre fortalezas del marketing mix: un análisis basado en redes neuronales artificiales || Export Intensity and Interaction between Marketing Mix: An Analysis based on Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Gutiérrez-Villar, Belén

    2014-12-01

    Full Text Available Entre los factores determinantes de la actuación exportadora de las empresas, numerosos estudios han subrayado la relevancia del mix de marketing. Generalmente, la mayoría de los estudios abordan el análisis de las variables centrado en estrategias específicas, en particular fenómenos de estandarización-adaptación. El presente estudio analiza si existe un efecto interactivo de fortalezas generadas en las diferentes variables del mix de marketing que pueda asociarse a diferentes perfiles exportadores. Para ello, se ha empleado el algoritmo Extreme Learning Machine (ELM dentro de los procedimientos Perceptrón Multicapa (MLP de Redes Neuronales Artificiales (RNA. Asimismo, el análisis se combina con un novedoso procedimiento de análisis de sensibilidad desarrollado ad hoc para este estudio, el cual permite conocer los efectos individuales e interactivos de las variables predictoras sobre la variable dependiente en problemas clasificatorios de naturaleza dicotómica. Los resultados obtenidos nos permiten corroborar la existencia de los efectos interactivos postulados, poniendo al mismo tiempo de manifiesto la utilidad de las RNA y del análisis de sensibilidad propuesto para la investigación en el área de marketing y, específicamente, para los estudios de internacionalización de empresas. || Among the determining factors in export activity, many studies have highlighted the relevance of the marketing mix. Generally, the majority of them use a variables analysis to focus on specific strategies, in particular, standardized-adaptations. This paper analyzes if there is an interactive effect of strength generated in different variables of the marketing mix that can be associated with different export profiles. The Extreme Learning Machine (ELM algorithm has been used within the Multilayer Perceptron (MLP of Artificial Neural Networks (ANN. In addition, the analyses combine a novel approach for sensitivity analysis developed ad hoc for this

  10. Monoclonal antibodies against muscle actin isoforms: epitope identification and analysis of isoform expression by immunoblot and immunostaining in normal and regenerating skeletal muscle [version 2; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Christine Chaponnier

    2016-06-01

    Full Text Available Higher vertebrates (mammals and birds express six different highly conserved actin isoforms that can be classified in three subgroups: 1 sarcomeric actins, α-skeletal (α-SKA and α-cardiac (α-CAA, 2 smooth muscle actins (SMAs, α-SMA and γ-SMA, and 3 cytoplasmic actins (CYAs, β-CYA and γ-CYA. The variations among isoactins, in each subgroup, are due to 3-4 amino acid differences located in their acetylated N-decapeptide sequence. The first monoclonal antibody (mAb against an actin isoform (α-SMA was produced and characterized in our laboratory in 1986 (Skalli  et al., 1986 . We have further obtained mAbs against the 5 other isoforms. In this report, we focus on the mAbs anti-α-SKA and anti-α-CAA obtained after immunization of mice with the respective acetylated N-terminal decapeptides using the Repetitive Immunizations at Multiple Sites Strategy (RIMMS. In addition to the identification of their epitope by immunoblotting, we describe the expression of the 2 sarcomeric actins in mature skeletal muscle and during muscle repair after micro-lesions. In particular, we analyze the expression of α-CAA, α-SKA and α-SMA by co-immunostaining in a time course frame during the muscle repair process. Our results indicate that a restricted myocyte population expresses α-CAA and suggest a high capacity of self-regeneration in muscle cells. These antibodies may represent a helpful tool for the follow-up of muscle regeneration and pathological changes.

  11. La participation des femmes à la vie politique se traduit par des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La participation des femmes à la vie politique se traduit par des économies locales plus vigoureuses. 08 juin 2016. Image. Des femmes assistent à une réunion d'un groupe d'entraide près d'. Edgard Rodriguez - IDRC. Des femmes assistent à une réunion d'un groupe d'entraide près d'Hyderabad, en Inde. Keenara ...

  12. statut de la matiere organique des cambisols et des lixisols sous

    African Journals Online (AJOL)

    Administrateur

    L'étude vise à évaluer la matière organique des Cambisols et des Lixisols sous formations naturelles de longue durée en zone climatique nord-soudanienne et à établir, les relations entre ... sont supérieures à celles des sols des zones sahélienne et sud-soudanienne. ... globale a eu une corrélation positive avec le pH.

  13. Renforcement de l'autonomie des collectivités au moyen des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention permettra au ministère des Communications et des Technologies de l'information de l'Égypte ainsi qu'au fonds spécial réservé aux TI de consolider le modèle actuel des clubs de TI en Égypte, par l'entremise de services d'assistance sur demande, d'activités de formation à l'intention du personnel des ...

  14. Accès à l'eau : des solutions techniques et sociales aident des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Grâce à la modélisation par ordinateur faisant appel à des techniques de pointe et à la consultation des collectivités, l'organisme bolivien Agua Sustentable a trouvé des solutions politiques à des conflits qui auraient pu s'avérer désastreux au sujet de l'accès à l'eau. Cet organisme de recherche subventionné par le CRDI a ...

  15. Connaissances, attitudes et pratiques des prestataires de santé des ...

    African Journals Online (AJOL)

    ... des prestataires interrogés avaient respectivement une bonne connaissance des facteurs de risque et des moyens de dépistage. Les signes évocateurs et les examens complémentaires nécessaires au diagnostic du cancer du sein étaient connus par 15,3 % des prestataires. La définition du cancer du sein et les moyens ...

  16. Incidence des prix et des taxes sur la consommation de produits du ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Incidence des prix et des taxes sur la consommation de produits du tabac en Argentine, en Bolivie et au Chili. Partout en Amérique du Sud, les adultes et les enfants font une grande consommation de tabac. Un nouveau projet de recherche se penchera sur les avantages et les limites des stratégies de fixation des prix et de ...

  17. La production mondiale des vins

    Directory of Open Access Journals (Sweden)

    Pierre GALET

    1969-09-01

     Le continent européen constitue le principal foyer de la culture de la vigne. Il vient en tête, non seulement par l'importance de la superficie cultivée, mais également par le volume global de la récolte et par la qualité des produits qui y sont récoltés : vins fins rouges, rosés et blancs, vins mousseux, vins de dessert ou vins généreux, eaux-de-vie, raisins de table frais et raisins secs. Les pays européens sont également les principaux consommateurs de vins du monde et la majeure partie des échanges commerciaux se font vers l'Europe ou partent de ce continent.

  18. Poser et reposer des choix.

    Directory of Open Access Journals (Sweden)

    Corinne Van Hauwermeiren- Echement

    2009-10-01

    Full Text Available IntroductionEn 1955, le legs de la collection Franckignoul – composée notamment d’un ensemble de quatre panneaux du XVIe siècle – vient enrichir les collections du Musée des Beaux-Arts de la Ville de Liège (Belgique. La fermeture de ce dernier en 1976 débouche sur  la scission des collections. Une partie est donnée au Musée de l’Art Wallon, l’autre partie allant au Musée d’Art Moderne et d’Art Contemporain (Mamac. Toutes les œuvres n’entrant pas dans ces deux collections sont reléguées en r...

  19. (TEC) et ciblage des pauvres au Mali

    International Development Research Centre (IDRC) Digital Library (Canada)

    Comment est-ce que c'est vrai. La preuve par … □ Différentiel de ciblage entre P et NP. □ Part normalisée de consommation/achat des Pauvres. □ Part normalisée de la pression fiscale. (totale et de porte) sur les achats des P. □ Part normalisée des "exonérations" revenant aux Pauvres ...

  20. ETUDE DE LA DISTRIBUTION DES CATIONS ECHANGEABLES

    African Journals Online (AJOL)

    SEI Joseph

    programme d'installations minières pour l'exploitation de l'or et du manganèse, intéressant des emprises foncières importantes. ... pour maitriser les risques liés aux sols pollués, lesquels peuvent conduire à des effets négatifs sur le long terme Meusy, & Giorni .... kaolinite et de type bentonite industrielle (SFBD). Le pH des ...

  1. Dynamik des Kaufverhaltens im Bio-Sortiment

    OpenAIRE

    Buder, Fabian; Hamm, Ulrich; Bickel, Malte; Bien, Barbara; Michels, Paul

    2010-01-01

    Das Gesamtziel des vorliegenden Forschungsprojekts war es, eine detaillierte Informationsgrundlage zum tatsächlichen Kaufverhalten von deutschen Haushalten bei ökologischen Lebensmitteln auf der Basis von Haushaltspaneldaten zu erstellen. Dazu sollten zum einen relevante Aspekte des Kaufverhaltens von Haushalten bei Öko-Lebensmitteln im Zeitverlauf von 2004 bis 2008 analysiert und zum anderen die Einflussfaktoren des Kaufverhaltens bei Öko-Lebensmitteln für das Jahr 2008 identifiziert werden....

  2. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    Directory of Open Access Journals (Sweden)

    Shinobu Tsuzuki

    2007-05-01

    Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

  3. Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics.

    Directory of Open Access Journals (Sweden)

    Chryso Kanthou

    Full Text Available Vascular endothelial growth factor-A (VEGF is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120 on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188 or wild type controls (fswt were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine

  4. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding

  5. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    International Nuclear Information System (INIS)

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding. Finally, I

  6. Revision des Symphurus du Siboga

    NARCIS (Netherlands)

    Chabanaud, Paul

    1955-01-01

    Ce m’est un devoir particulièrement agréable que de saisir l’occasion de ce petit mémoire pour remercier M. L. F. DE BEAUFORT, M. H. ENGEL, Directeur du Zoologisch Museum, ainsi que M. J. J. HOEDEMAN de l’accueil qu’à diverses reprises, j’ai reçu de leur part, au Zoölogisch Museum, et aussi des

  7. Contribution des TICs à l'abandon des mutilations génitales ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Contribution des TIC à l'abandon des MGF en Afrique de l'Ouest francophone : rôle des jeunes citoyennes; rapport technique no. 5 (rapport technique final), 18 octobre 2008 - 31 mars 2009. Download PDF. Related content. New website will help record vital life events to improve access to services for all. A new website ...

  8. Etat des lieux de la gestion des insecticides au Togo, Afrique de l ...

    African Journals Online (AJOL)

    Pour parvenir à une gestion optimale des maladies à transmission vectorielle ou tout au moins la nuisance culicidienne, une surveillance permanente des facteurs de risque devient nécessaire. Le principal facteur de risque est le vecteur qui transmet la maladie, et le contrôle du vecteur passe par des stratégies de lutte qui ...

  9. Ethnobotanique des plantes médicinales anti hémorroïdaires des ...

    African Journals Online (AJOL)

    SARAH

    2015-12-31

    Dec 31, 2015 ... but est de valoriser la médecine à base des plantes dans le traitement des pathologies ... médicinales anti hémorroïdaires et le coût réduit des recettes serait pour les populations démunies, ...... l'Afrique, Unesco/Aetfat/Unso.

  10. La production mondiale des vins

    Directory of Open Access Journals (Sweden)

    Pierre GALET

    1972-06-01

    Full Text Available La culture de la vigne en Autriche remonterait à l'occupation romaine, les premières plantations ayant été faites par les légions romaines de l'empereur Probus, dans la seconde moitié du IIIe siècle (Probus était né à Sirmium près du Danube et il favorisa l'extension des vignobles dans cette région pour approvisionner ses armées. Après la chute de l'empire romain et les invasions des Awares, on doit à Charlemagne le renouveau de la culture de la vigne, notamment dans la Wachau, en Basse- Autriche. Puis plus tard, à chaque avance de la colonisation, les vignes se répandirent sur les bords du Danube et dans les vallées latérales, l'extension étant favorisée par les communautés religieuses catholiques qui devinrent propriétaires de grands vignobles. La navigation sur le fleuve fut également un facteur favorable pour la culture de la vigne. Au XVIe siècle, apogée des cultures, le vin se vendait jusqu'en Pologne et dans les Etats Baltes.

  11. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

    Directory of Open Access Journals (Sweden)

    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  12. SSP: an interval integer linear programming for de novo transcriptome assembly and isoform discovery of RNA-seq reads.

    Science.gov (United States)

    Safikhani, Zhaleh; Sadeghi, Mehdi; Pezeshk, Hamid; Eslahchi, Changiz

    2013-01-01

    Recent advances in the sequencing technologies have provided a handful of RNA-seq datasets for transcriptome analysis. However, reconstruction of full-length isoforms and estimation of the expression level of transcripts with a low cost are challenging tasks. We propose a novel de novo method named SSP that incorporates interval integer linear programming to resolve alternatively spliced isoforms and reconstruct the whole transcriptome from short reads. Experimental results show that SSP is fast and precise in determining different alternatively spliced isoforms along with the estimation of reconstructed transcript abundances. The SSP software package is available at http://www.bioinf.cs.ipm.ir/software/ssp. © 2013.

  13. Modalites de consommation et valeur nutritionnelle des ...

    African Journals Online (AJOL)

    Les légumineuses niébé, voandzou et zamnè sont consommées sous forme de ragout et de plats associés à des céréales respectivement par 99%, 93% et 76%. L'arachide et le soja sont utilisés comme des ingrédients ou comme des collations. Les légumineuses ont des teneurs importantes en protéines, 35,76%, 31,04%, ...

  14. EFFET DES TRAITEMENTS THERMIQUES SUR LA REACTION ENTRE DES COUCHES MINCES DE TITANE ET DES SUBSTRATS EN ACIER

    Directory of Open Access Journals (Sweden)

    D Slimani

    2015-06-01

    Full Text Available Des couches minces du titane pur ont été déposées avec la méthode de pulvérisation cathodique sur des substrats en acier, type FF80 K-1 contenants ~1% mass. en carbone. La réaction entre les deux parties du système substrat-couche mince est activée avec des traitements thermiques sous vide dans l’intervalle de températures de 400 à900°Cpendant 30 minutes. Les Spectres de diffraction de rayons x confirment l’inter- diffusion des éléments  chimiques du système résultants la formation et la croissance des nouvelles phases en particulier le carbure binaire TiC ayant des caractéristiques thermomécaniques importantes. L’analyse morphologique des échantillons traités  avec le microscope électronique à balayage (MEB montre l’augmentation du flux de diffusion atomique avec la température de recuit, notamment la diffusion du manganèse et du fer vers la surface libre des échantillons aux températures élevées provoquant la dégradation des propriétés mécaniques des revêtements contrairement au premiers stades d’interaction où on a obtenu des bonnes valeurs de la microdureté.

  15. Développer le leadership dans des villes de l'Amérique latine et des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Développer le leadership dans des villes de l'Amérique latine et des Caraïbes dans le contexte des changements climatiques. En raison des changements climatiques, de la croissance démographique et de l'urbanisation rapide non planifiée, les villes des pays en développement sont à la fois le principal déclencheur des ...

  16. Deep Proteomics of Mouse Skeletal Muscle Enables Quantitation of Protein Isoforms, Metabolic Pathways, and Transcription Factors*

    Science.gov (United States)

    Deshmukh, Atul S.; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T.; Cox, Jürgen; Mann, Matthias

    2015-01-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. PMID:25616865

  17. Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

    2017-01-01

    Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

  18. Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry

    Directory of Open Access Journals (Sweden)

    Linda V. Hjørnevik

    2015-12-01

    Full Text Available Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s. A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin.

  19. Hemoglobin isoform differentiation and allosteric regulation of oxygen binding in the turtle, Trachemys scripta

    DEFF Research Database (Denmark)

    Damsgaard, Christian; Storz, Jay F.; Hoffmann, Federico G.

    2013-01-01

    When freshwater turtles acclimatize to winter hibernation, there is a gradual transition from aerobic to anaerobic metabolism, which may require adjustments of blood O2 transport before turtles become anoxic. Here, we report the effects of protons, anionic cofactors, and temperature on the O2......-binding properties of isolated hemoglobin (Hb) isoforms, HbA and HbD, in the turtle Trachemys scripta. We determined the primary structures of the constituent subunits of the two Hb isoforms, and we related the measured functional properties to differences in O2 affinity between untreated hemolysates from...... turtles that were acclimated to normoxia and anoxia. Our data show that HbD has a consistently higher O2 affinity compared with HbA, whereas Bohr and temperature effects, as well as thiol reactivity, are similar. Although sequence data show amino acid substitutions at two known β-chain ATP-binding site...

  20. alpha isoforms of soluble and membrane-linked folate-binding protein in human blood

    DEFF Research Database (Denmark)

    Hoier-Madsen, M.; Holm, J.; Hansen, S.I.

    2008-01-01

    supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FR alpha isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBP alpha. The alpha isoforms identified on erythrocyte membranes......, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP The FBP alpha in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBP alpha (>120 kDa), which could represent receptor...... fragments from decomposed erythrocytes and granulocytes. The soluble FBPs may exert bacteriostatic effects and protect folates in plasma from biological degradation, whereas FRs on the surface of blood cells could be involved in intracellular folate uptake or serve as signal proteins. The latter receptors...

  1. Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

    Science.gov (United States)

    Zhao, Y; Fung, C; Shin, D; Shin, B-C; Thamotharan, S; Sankar, R; Ehninger, D; Silva, A; Devaskar, S U

    2010-03-01

    Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

  2. Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse.

    Science.gov (United States)

    Besalduch, Núria; Tomàs, Marta; Santafé, Manel M; Garcia, Neus; Tomàs, Josep; Lanuza, Maria Angel

    2010-01-10

    Protein kinase C (PKC) is essential for signal transduction in a variety of cells, including neurons and myocytes, and is involved in both acetylcholine release and muscle fiber contraction. Here, we demonstrate that the increases in synaptic activity by nerve stimulation couple PKC to transmitter release in the rat neuromuscular junction and increase the level of alpha, betaI, and betaII isoforms in the membrane when muscle contraction follows the stimulation. The phosphorylation activity of these classical PKCs also increases. It seems that the muscle has to contract in order to maintain or increase classical PKCs in the membrane. We use immunohistochemistry to show that PKCalpha and PKCbetaI were located in the nerve terminals, whereas PKCalpha and PKCbetaII were located in the postsynaptic and the Schwann cells. Stimulation and contraction do not change these cellular distributions, but our results show that the localization of classical PKC isoforms in the membrane is affected by synaptic activity.

  3. FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch

    Science.gov (United States)

    Day, Nancy F; Kimball, Todd Haswell; Aamodt, Caitlin M; Heston, Jonathan B; Hilliard, Austin T; Xiao, Xinshu; White, Stephanie A

    2018-01-01

    Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans. PMID:29360038

  4. Impact de la preparation des anodes crues et des conditions de cuisson sur la fissuration dans des anodes denses

    Science.gov (United States)

    Amrani, Salah

    La fabrication de l'aluminium est realisee dans une cellule d'electrolyse, et cette operation utilise des anodes en carbone. L'evaluation de la qualite de ces anodes reste indispensable avant leur utilisation. La presence des fissures dans les anodes provoque une perturbation du procede l'electrolyse et une diminution de sa performance. Ce projet a ete entrepris pour determiner l'impact des differents parametres de procedes de fabrication des anodes sur la fissuration des anodes denses. Ces parametres incluent ceux de la fabrication des anodes crues, des proprietes des matieres premieres et de la cuisson. Une recherche bibliographique a ete effectuee sur tous les aspects de la fissuration des anodes en carbone pour compiler les travaux anterieurs. Une methodologie detaillee a ete mise au point pour faciliter le deroulement des travaux et atteindre les objectifs vises. La majorite de ce document est reservee pour la discussion des resultats obtenus au laboratoire de l'UQAC et au niveau industriel. Concernant les etudes realisees a l'UQAC, une partie des travaux experimentaux est reservee a la recherche des differents mecanismes de fissuration dans les anodes denses utilisees dans l'industrie d'aluminium. L'approche etait d'abord basee sur la caracterisation qualitative du mecanisme de la fissuration en surface et en profondeur. Puis, une caracterisation quantitative a ete realisee pour la determination de la distribution de la largeur de la fissure sur toute sa longueur, ainsi que le pourcentage de sa surface par rapport a la surface totale de l'echantillon. Cette etude a ete realisee par le biais de la technique d'analyse d'image utilisee pour caracteriser la fissuration d'un echantillon d'anode cuite. L'analyse surfacique et en profondeur de cet echantillon a permis de voir clairement la formation des fissures sur une grande partie de la surface analysee. L'autre partie des travaux est basee sur la caracterisation des defauts dans des echantillons d'anodes crues

  5. Revealing the functions of the transketolase enzyme isoforms in Rhodopseudomonas palustris using a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Hu

    Full Text Available BACKGROUND: Rhodopseudomonas palustris (R. palustris is a purple non-sulfur anoxygenic phototrophic bacterium that belongs to the class of proteobacteria. It is capable of absorbing atmospheric carbon dioxide and converting it to biomass via the process of photosynthesis and the Calvin-Benson-Bassham (CBB cycle. Transketolase is a key enzyme involved in the CBB cycle. Here, we reveal the functions of transketolase isoforms I and II in R. palustris using a systems biology approach. METHODOLOGY/PRINCIPAL FINDINGS: By measuring growth ability, we found that transketolase could enhance the autotrophic growth and biomass production of R. palustris. Microarray and real-time quantitative PCR revealed that transketolase isoforms I and II were involved in different carbon metabolic pathways. In addition, immunogold staining demonstrated that the two transketolase isoforms had different spatial localizations: transketolase I was primarily associated with the intracytoplasmic membrane (ICM but transketolase II was mostly distributed in the cytoplasm. Comparative proteomic analysis and network construction of transketolase over-expression and negative control (NC strains revealed that protein folding, transcriptional regulation, amino acid transport and CBB cycle-associated carbon metabolism were enriched in the transketolase I over-expressed strain. In contrast, ATP synthesis, carbohydrate transport, glycolysis-associated carbon metabolism and CBB cycle-associated carbon metabolism were enriched in the transketolase II over-expressed strain. Furthermore, ATP synthesis assays showed a significant increase in ATP synthesis in the transketolase II over-expressed strain. A PEPCK activity assay showed that PEPCK activity was higher in transketolase over-expressed strains than in the negative control strain. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the two isoforms of transketolase in R. palustris could affect photoautotrophic growth

  6. Muscle-Type Specific Autophosphorylation of CaMKII Isoforms after Paced Contractions

    Directory of Open Access Journals (Sweden)

    Wouter Eilers

    2014-01-01

    Full Text Available We explored to what extent isoforms of the regulator of excitation-contraction and excitation-transcription coupling, calcium/calmodulin protein kinase II (CaMKII contribute to the specificity of myocellular calcium sensing between muscle types and whether concentration transients in its autophosphorylation can be simulated. CaMKII autophosphorylation at Thr287 was assessed in three muscle compartments of the rat after slow or fast motor unit-type stimulation and was compared against a computational model (CaMuZclE coupling myocellular calcium dynamics with CaMKII Thr287 phosphorylation. Qualitative differences existed between fast- (gastrocnemius medialis and slow-type muscle (soleus for the expression pattern of CaMKII isoforms. Phospho-Thr287 content of δA CaMKII, associated with nuclear functions, demonstrated a transient and compartment-specific increase after excitation, which contrasted to the delayed autophosphorylation of the sarcoplasmic reticulum-associated βM CaMKII. In soleus muscle, excitation-induced δA CaMKII autophosphorylation demonstrated frequency dependence (P = 0.02. In the glycolytic compartment of gastrocnemius medialis, CaMKII autophosphorylation after excitation was blunted. In silico assessment emphasized the importance of mitochondrial calcium buffer capacity for excitation-induced CaMKII autophosphorylation but did not predict its isoform specificity. The findings expose that CaMKII autophosphorylation with paced contractions is regulated in an isoform and muscle type-specific fashion and highlight properties emerging for phenotype-specific regulation of CaMKII.

  7. Heterogeneity of serum gelatinases MMP-2 and MMP-9 isoforms and charge variants

    Science.gov (United States)

    Rossano, Rocco; Larocca, Marilena; Riviello, Lea; Coniglio, Maria Gabriella; Vandooren, Jennifer; Liuzzi, Grazia Maria; Opdenakker, Ghislain; Riccio, Paolo

    2014-01-01

    The matrix metalloproteinases (MMPs) gelatinase A (MMP-2) and gelatinase B (MMP-9) are mediators of brain injury in multiple sclerosis (MS) and valuable biomarkers of disease activity. We applied bidimensional zymography (2-DZ) as an extension of classic monodimensional zymography (1-DZ) to analyse the complete pattern of isoforms and post-translational modifications of both MMP-9 and MMP-2 present in the sera of MS patients. The enzymes were separated on the basis of their isoelectric points (pI) and apparent molecular weights (Mw) and identified both by comparison with standard enzyme preparations and by Western blot analysis. Two MMP-2 isoforms, and at least three different isoforms and two different states of organization of MMP-9 (the multimeric MMP-9 and the N-GAL-MMP-9 complex) were observed. In addition, 2-DZ revealed for the first time that all MMP-9 and MMP-2 isoforms actually exist in the form of charge variants: four or five variants in the N-GAL complex, more charge variants in the case of MMP-9; and five to seven charge variants for MMP-2. Charge variants were also observed in recombinant enzymes and, after concentration, also in sera from healthy individuals. Sialylation (MMP-9) and phosphorylation (MMP-2) contributed to molecular heterogeneity. The detection of charge variants of MMP-9 and MMP-2 in MS serum samples illustrates the power of 2-DZ and demonstrates that in previous studies MMP mixtures, rather than single molecules, were analysed. These observations open perspectives for better diagnosis and prognosis of many diseases and need to be critically interpreted when applying other methods for MS and other diseases. PMID:24616914

  8. Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

    OpenAIRE

    Fabian V Filipp

    2013-01-01

    Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor acti...

  9. Characterization of Alien isoforms in vertebrates : Caracterización de isoformas de Alien en vertebrados

    OpenAIRE

    Tenbaum, Stephan

    2002-01-01

    Alien protein isoforms have been described to be involved in a number of biological processes. Alienalpha is a corepressor of the thyroid hormone receptor mediating transcriptional repression in a ligand-sensitive manner. Furthermore, Alienalpha is a corepressor for the orphan receptor DAX1 and the vitamin-D3 receptor. Alienbetta/CSN2 is part of the COP9-signalosome complex that acts in protein phosphorylation, protein degradation and cell cycle regulation. The major goal of this...

  10. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.

    OpenAIRE

    Reith, A D; Ellis, C; Lyman, S D; Anderson, D M; Williams, D E; Bernstein, A; Pawson, T

    1991-01-01

    Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse development. We have analysed the interactions of normal and mutant W/c-kit gene products with cytoplasmic signalling proteins, using transient c-kit expression assays in COS cells. In addition to the previously identified c-kit gene product (Kit+), a second normal Kit isoform (KitA+) containing an i...

  11. Role of L-type Ca2+ channel isoforms in the extinction of conditioned fear.

    Science.gov (United States)

    Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J; Striessnig, Jörg; Singewald, Nicolas

    2008-05-01

    Dihydropyridine (DHP) L-type Ca(2+) channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the treatment of specific anxiety disorders. Ca(V)1.2 and Ca(V)1.3 are the predominant LTCCs in the mammalian brain. However, since no isoform-selective DHP blockers are available, their individual contribution to fear memory extinction is unknown. We used a novel mouse model expressing DHP-insensitive Ca(V)1.2 LTCCs (Ca(V)1.2DHP(-/-) mice) to address this question. In line with previous studies, wild-type (WT) mice treated with systemic nifedipine displayed markedly impaired fear extinction. This DHP effect was completely abolished in Ca(V)1.2DHP(-/-) mice, indicating that it is mediated by Ca(V)1.2, but not by Ca(V)1.3 LTCCs. Supporting this conclusion, Ca(V)1.3-deficient mice (Ca(V)1.3(-/-)) showed extinction identical to the respective WT mice. The inhibition of fear extinction was not observed after intracerebroventricular (i.c.v.) application of different doses of nifedipine, suggesting that this effect is secondary to inhibition of peripheral Ca(V)1.2 channels. The LTCC activator BayK, which lacks neurotoxic effects in Ca(V)1.2DHP(-/-) mice, did not influence the extinction time course. In summary, we demonstrate that LTCC signaling through the Ca(V)1.2 isoform of LTCCs interferes with fear memory extinction, presumably via a peripherally mediated mechanism. Activation of other LTCC isoforms (predominantly Ca(V)1.3) is not sufficient to accelerate extinction of conditioned fear in mice.

  12. Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia.

    Science.gov (United States)

    Wang, Rong; Feng, Wenli; Yang, Feifei; Yang, Xiao; Wang, Lina; Chen, Chong; Hu, Yuting; Ren, Qian; Zheng, Guoguang

    2018-02-01

    Macrophage colony-stimulating factor (M-CSF) regulates both malignant cells and microenvironmental cells. Its splicing isoforms show functional heterogeneity. However, their roles on leukemia have not been well established. Here, the expression of total M-CSF in patients with hematopoietic malignancies was analyzed. The roles of M-CSF isoforms on the progression of acute myeloid leukemia (AML) were studied by establishing MLL-AF9-induced mouse AML models with high level membrane-bound M-CSF (mM-CSF) or soluble M-CSF (sM-CSF). Total M-CSF was highly expressed in myeloid leukemia patients. Furthermore, mM-CSF but not sM-CSF prolonged the survival of leukemia mice. While sM-CSF was more potent to promote proliferation and self-renew, mM-CSF was more potent to promote differentiation. Moreover, isoforms had different effects on leukemia-associated macrophages (LAMs) though they both increase monocytes/macrophages by growth-promoting and recruitment effects. In addition, mM-CSF promoted specific phagocytosis of leukemia cells by LAMs. RNA-seq analysis revealed that mM-CSF enhanced phagocytosis-associated genes and activated oxidative phosphorylation and metabolism pathway. These results highlight heterogeneous effects of M-CSF isoforms on AML progression and the mechanisms of mM-CSF, that is, intrinsically promoting AML cell differentiation and extrinsically enhancing infiltration of macrophages and phagocytosis by macrophages, which may provide potential clues for clinical diagnosis and therapy. © 2017 Australasian Society for Immunology Inc.

  13. Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

    Science.gov (United States)

    Fornai, M; Colucci, R; Antonioli, L; Ippolito, C; Segnani, C; Buccianti, P; Marioni, A; Chiarugi, M; Villanacci, V; Bassotti, G; Blandizzi, C; Bernardini, N

    2014-08-01

    The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. © 2014 The British Pharmacological Society.

  14. Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4

    International Nuclear Information System (INIS)

    Tang, Juan; Zheng, Hanxi; Chen, Ling; Gao, Shangshang; Shi, Xiaorui; Liu, Jingjing; Xu, Lan

    2017-01-01

    The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. - Highlights: • ppGalNAc-T1 and T4 are highly expressed during MC3T3 cell osteogenesis. • Knockdown of ppGalNAc-T1 and -T4 decreases osteogenic differentiation and mineralization. • Expression of osteogenic factors are differentially affected by decreased ppGalNAc-T1 and -T4 expression.

  15. Smoking specifically induces metallothionein-2 isoform in human placenta at term

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Garrido, Fernando; Llanos, Miguel N.

    2006-01-01

    Recently, we reported the presence of higher levels of metallothionein (MT) in placentas of smokers compared to non-smokers. In the present study, we designed experiments to separate and evaluate two isoforms of MT (MT-1 and MT-2) in placentas of smokers and non-smokers. Metallothionein was extracted and separated by ion-exchange high performance liquid chromatography (HPLC), previous saturation with cadmium chloride. Two peaks eluting at 6 and 12.5 min, corresponding to MT-1 and MT-2, respectively, were obtained. Metallothionein present in both peaks was identified by Western blot analysis using a monoclonal antibody directed against MT-1 and MT-2. Each isoform concentration was calculated after measuring its cadmium content by atomic absorption spectrometry with inductively coupled-plasma. In placentas of smokers, MT-2 levels increased by seven-fold compared to non-smokers, whereas MT-1 was not changed. Total placental cadmium and zinc concentrations, determined by atomic absorption spectrometry and neutron activation analysis, respectively, were higher in smokers. Metallothioneins levels were clearly in excess to bind all cadmium ions present in placentas. However, most of placental zinc remains unbound to MTs, although as much as twice zinc ions could be bound to MT in smokers. In conclusion, MT-2 is the main isoform induced by smoking, suggesting that this isoform could be involved in placental cadmium and zinc retention. This fact, which could contribute to reduce the transference of zinc to the fetus, may be associated to detrimental effects on fetal growth and development

  16. The Role of a Novel Myosin Isoform in Prostate Cancer Metastasis

    Science.gov (United States)

    2013-10-01

    2013 Accepted 14 February 2013 Available online 21 February 2013 Keywords: Myosin IC Isoforms Nucleolar localization signal Nucleolus Nucleus RNA...polymerase I Fibrillarinnt matter & 2013 Elsevier 1016/j.yexcr.2013.02.008 S, nucleolar localization ; No, nucleolus ; N, nucle bovine serum albumin; S...the nucleus, and the nucleolus . In the cytoplasm, myosin IC associ- ates with membranes and is involved in vesicle transport of membrane proteins [2

  17. Deregulation of the endogenous C/EBPβ LIP isoform predisposes to tumorigenesis.

    Science.gov (United States)

    Bégay, Valérie; Smink, Jeske J; Loddenkemper, Christoph; Zimmermann, Karin; Rudolph, Cornelia; Scheller, Marina; Steinemann, Doris; Leser, Ulf; Schlegelberger, Brigitte; Stein, Harald; Leutz, Achim

    2015-01-01

    Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPβ) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPβ mRNA. The truncated C/EBPβ LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPβ LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPβ knockin mice that constitutively express only the C/EBPβ LIP isoform from its own locus. Our data show that deregulated C/EBPβ LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPβ LIP supports a pro-tumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/EBPβ LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPβ LIP isoform. Elevated C/EBPβ LIP promotes cancer in mice. C/EBPβ LIP is upregulated in B-NHL. Deregulated C/EBPβ LIP alters apoptosis and cytokine/chemokine networks. Deregulated C/EBPβ LIP may support a pro-tumorigenic microenvironment.

  18. VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Fang; Li, Xiuli [Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing (China); Kong, Jian [Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing (China); Pan, Bing [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Sun, Min [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xian (China); Zheng, Lemin, E-mail: zhengl@bjmu.edu.cn [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Yao, Yuanqing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing (China)

    2013-11-08

    Highlights: •We discovered a new member of VEGFxxxb family-VEGF111b. •We found VEGF111b mRNA and protein can be induced by mitomycin C. •We confirmed VEGF111b over-expression inhibits angiogenesis. •VEGF111b inhibits angiogenesis through inhibiting VEGF-R2/PI3K/Akt and VEGF-R2/ERK1/2 phosphorylation. -- Abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA{sub 3.1} empty vector, pcDNA{sub 3.1}-VEGF111b or pcDNA{sub 3.1}-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth.

  19. VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis

    International Nuclear Information System (INIS)

    Gu, Fang; Li, Xiuli; Kong, Jian; Pan, Bing; Sun, Min; Zheng, Lemin; Yao, Yuanqing

    2013-01-01

    Highlights: •We discovered a new member of VEGFxxxb family-VEGF111b. •We found VEGF111b mRNA and protein can be induced by mitomycin C. •We confirmed VEGF111b over-expression inhibits angiogenesis. •VEGF111b inhibits angiogenesis through inhibiting VEGF-R2/PI3K/Akt and VEGF-R2/ERK1/2 phosphorylation. -- Abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA 3.1 empty vector, pcDNA 3.1 -VEGF111b or pcDNA 3.1 -VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth

  20. Improved mass spectrometry assay for plasma hepcidin: detection and characterization of a novel hepcidin isoform.

    Directory of Open Access Journals (Sweden)

    Coby M M Laarakkers

    Full Text Available Mass spectrometry (MS-based assays for the quantification of the iron regulatory hormone hepcidin are pivotal to discriminate between the bioactive 25-amino acid form that can effectively block the sole iron transporter ferroportin and other naturally occurring smaller isoforms without a known role in iron metabolism. Here we describe the design, validation and use of a novel stable hepcidin-25(+40 isotope as internal standard for quantification. Importantly, the relative large mass shift of 40 Da makes this isotope also suitable for easy-to-use medium resolution linear time-of-flight (TOF platforms. As expected, implementation of hepcidin-25(+40 as internal standard in our weak cation exchange (WCX TOF MS method yielded very low inter/intra run coefficients of variation. Surprisingly, however, in samples from kidney disease patients, we detected a novel peak (m/z 2673.9 with low intensity that could be identified as hepcidin-24 and had previously remained unnoticed due to peak interference with the formerly used internal standard. Using a cell-based bioassay it was shown that synthetic hepcidin-24 was, like the -22 and -20 isoforms, a significantly less potent inducer of ferroportin degradation than hepcidin-25. During prolonged storage of plasma at room temperature, we observed that a decrease in plasma hepcidin-25 was paralleled by an increase in the levels of the hepcidin-24, -22 and -20 isoforms. This provides first evidence that all determinants for the conversion of hepcidin-25 to smaller inactive isoforms are present in the circulation, which may contribute to the functional suppression of hepcidin-25, that is significantly elevated in patients with renal impairment. The present update of our hepcidin TOF MS assay together with improved insights in the source and preparation of the internal standard, and sample stability will further improve our understanding of circulating hepcidin and pave the way towards further optimization and

  1. Using XML to encode TMA DES metadata

    Directory of Open Access Journals (Sweden)

    Oliver Lyttleton

    2011-01-01

    Full Text Available Background: The Tissue Microarray Data Exchange Specification (TMA DES is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  2. Using XML to encode TMA DES metadata.

    Science.gov (United States)

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  3. Using XML to encode TMA DES metadata

    Science.gov (United States)

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs. PMID:21969921

  4. Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity

    International Nuclear Information System (INIS)

    Brunkhorst, Adrian; Neuman, Toomas; Hall, Anita; Arenas, Ernest; Bartfai, Tamas; Hermanson, Ola; Metsis, Madis

    2004-01-01

    The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF II 135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo

  5. Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    El Eter, E. [Physiology Department, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Cardiovascular Research Group, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Physiology Department, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Al-Masri, A.A. [Physiology Department, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia); Cardiovascular Research Group, Faculty of Medicine, King Saud University, Riyadh (Saudi Arabia)

    2015-03-03

    The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors.

  6. Differential expression of a new isoform of DLG2 in renal oncocytoma

    Directory of Open Access Journals (Sweden)

    Kovacs Gyula

    2006-04-01

    Full Text Available Abstract Background Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type. Methods In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis. Results We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour. Conclusion The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma.

  7. Adaptive evolution and elucidating the potential inhibitor against schizophrenia to target DAOA (G72) isoforms.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Mannan, Shazia; Kanwal, Sumaira; Naveed, Ishrat; Mir, Asif

    2015-01-01

    Schizophrenia (SZ), a chronic mental and heritable disorder characterized by neurophysiological impairment and neuropsychological abnormalities, is strongly associated with D-amino acid oxidase activator (DAOA, G72). Research studies emphasized that overexpression of DAOA may be responsible for improper functioning of neurotransmitters, resulting in neurological disorders like SZ. In the present study, a hybrid approach of comparative modeling and molecular docking followed by inhibitor identification and structure modeling was employed. Screening was performed by two-dimensional similarity search against selected inhibitor, keeping in view the physiochemical properties of the inhibitor. Here, we report an inhibitor compound which showed maximum binding affinity against four selected isoforms of DAOA. Docking studies revealed that Glu-53, Thr-54, Lys-58, Val-85, Ser-86, Tyr-87, Leu-88, Glu-90, Leu-95, Val-98, Ser-100, Glu-112, Tyr-116, Lys-120, Asp-121, and Arg-122 are critical residues for receptor-ligand interaction. The C-terminal of selected isoforms is conserved, and binding was observed on the conserved region of isoforms. We propose that selected inhibitor might be more potent on the basis of binding energy values. Further analysis of this inhibitor through site-directed mutagenesis could be helpful for exploring the details of ligand-binding pockets. Overall, the findings of this study may be helpful in designing novel therapeutic targets to cure SZ.

  8. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair

    International Nuclear Information System (INIS)

    Liu, Hongbing; Herrmann, Christine H.; Chiang, Karen; Sung, Tzu-Ling; Moon, Sung-Hwan; Donehower, Lawrence A.; Rice, Andrew P.

    2010-01-01

    Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.

  9. Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell tumorigenesis.

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y; Tsai, Ming-Jer; O'Malley, Bert W

    2008-10-01

    Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in human kidney cells and suppresses anchorage-independent growth and xenograft tumor formation. Suppression occurs in part by down-regulating c-myc and its downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced G(1)-S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma compared with normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform. This is, thus far, the only example of a nuclear receptor coregulator involved in suppression of kidney cancer and suggests potentially significant new roles for coregulators in renal cancer biology.

  10. Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1

    Science.gov (United States)

    Inserra, Marco C.; Israel, Mathilde R.; Caldwell, Ashlee; Castro, Joel; Deuis, Jennifer R.; Harrington, Andrea M.; Keramidas, Angelo; Garcia-Caraballo, Sonia; Maddern, Jessica; Erickson, Andelain; Grundy, Luke; Rychkov, Grigori Y.; Zimmermann, Katharina; Lewis, Richard J.; Brierley, Stuart M.; Vetter, Irina

    2017-01-01

    Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1–1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1.8, while the slope factor of the conductance-voltage curves was significantly increased for NaV1.7 and peak current was significantly increased for NaV1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of NaV1.8 and the tetrodotoxin-sensitive isoforms NaV1.7 and NaV1.6, respectively. The contribution of these isoforms to excitability of peripheral C- and A-fibre sensory neurons, confirmed using murine skin and visceral single-fibre recordings, reflects the expression pattern of NaV isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation. PMID:28225079

  11. Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    El Eter, E.; Al-Masri, A.A.

    2015-01-01

    The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors

  12. Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

    Science.gov (United States)

    Caiozzo, V. J.; Herrick, R. E.; Baldwin, K. M.

    1992-01-01

    This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

  13. Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

    Science.gov (United States)

    Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. © 2015 The Author(s).

  14. Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance

    Directory of Open Access Journals (Sweden)

    L. Michael Carastro

    2014-01-01

    Full Text Available Background. Molecular markers for prostate cancer (PCa risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31–0.99 was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57–1.00, P=0.053 as well as PCa specific death (HR = 0.69, 95%Cl = 0.45–1.06, P=0.09. Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P<0.001. Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

  15. Analysis of human articular chondrocyte CD44 isoform expression and function in health and disease.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S; Lawson, M F; Hughes, D E; Dunne, E

    1996-08-01

    Interactions between articular chondrocytes and components of the extracellular matrix are of potential importance in the normal function of cartilage and in the pathophysiology of arthritis. Little is known of the basis of these interactions, but cell adhesive molecules such as CD44 are likely to be involved. Immunohistology using six well-characterized anti-CD44 monoclonal antibodies demonstrated standard CD44 isoform (CD44H) expression by all chondrocytes in normal and osteoarthrotic (OA) cartilage but absence of the CD44E variant. Polymerase chain reaction (PCR) of reverse transcribed mRNA from monolayer cultures of normal and OA chondrocytes using primer sequences which span the region containing variably spliced exons produced a predominant band representing the standard form of CD44, which lacks the variable exons 6-15 (v1-v10). No product was seen at the expected size of the epithelial variant of CD44 (CD44v8-10). Use of exon-specific primers, however, showed expression of variant exons resulting in multiple minor isoforms. Standard CD44 was also shown to be the predominantly expressed isoform identified by immunoprecipitation, but human articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44 may function as an adhesion receptor for other matrix molecules such as fibronectin or collagen.

  16. mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome

    Directory of Open Access Journals (Sweden)

    Beatriz Puisac

    2017-02-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the NIPBL gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction. Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of NIPBL (c.8387A > G; P.Tyr2796Cys, showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.

  17. Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

    National Research Council Canada - National Science Library

    Cadieux, Chantal

    2008-01-01

    Short CUX1 isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression...

  18. Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

    National Research Council Canada - National Science Library

    Cadieux, Chantal

    2007-01-01

    Short CDP/Cux isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression...

  19. Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

    Directory of Open Access Journals (Sweden)

    Rachel S. Lee

    2011-01-01

    Full Text Available The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.

  20. Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased dogs with joint diseases or other conditions

    DEFF Research Database (Denmark)

    Kjelgaard-Hansen, Mads Jens; Christensen, Michelle B.; Lee, Marcel Huisung

    2007-01-01

    Serum amyloid A (SAA) is a major acute phase protein in dogs. However, knowledge of qualitative properties of canine SAA and extent of its synthesis in extrahepatic tissues is limited. The aim of the study was to investigate expression of different SAA isoforms in serum and synovial fluid...... in samples obtained from dogs (n = 16) suffering from different inflammatory or non-inflammatory conditions, which were either related or unrelated to joints. Expression of SAA isoforms was visualized by denaturing isoelectric focusing and Western blotting. Serum amyloid A was present in serum from all dogs...... with systemic inflammatory activity, and up to four major isoforms with apparent isoelectric points between 6.1 and 7.9 were identified. In synovial fluid from inflamed joints one or more highly alkaline SAA isoforms (with apparent isoelectric points above 9.3) were identified, with data suggesting local...

  1. EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Chevreux, Sylviane; Roudeau, Stephane; Deves, Guillaume; Ortega, Richard [Laboratoire de Chimie Nucleaire Analytique et Bioenvironnementale, CNRS UMR5084, Universite Bordeaux 1, Chemin du Solarium, F-33175 Gradignan cedex (France); Solari, Pier Lorenzo [Synchrotron SOLEIL, L' Orme des Merisiers, BP 48, F-91192 Gif-sur-Yvette cedex, Saint-Aubin (France); Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis, E-mail: ortega@cenbg.in2p3.f [FAME, ESRF, 6 rue Jules Horowitz, BP220, F-38043 Grenoble cedex (France)

    2009-11-15

    Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

  2. EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

    Science.gov (United States)

    Chevreux, Sylviane; Solari, Pier Lorenzo; Roudeau, Stéphane; Deves, Guillaume; Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis; Ortega, Richard

    2009-11-01

    Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

  3. EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

    International Nuclear Information System (INIS)

    Chevreux, Sylviane; Roudeau, Stephane; Deves, Guillaume; Ortega, Richard; Solari, Pier Lorenzo; Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis

    2009-01-01

    Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

  4. Does Increased Expression of the Plasma Membrane Calcium-ATPase Isoform 2 Confer Resistance to Apoptosis on Breast Cancer Cells?

    National Research Council Canada - National Science Library

    VanHouten, Joshua N

    2008-01-01

    The plasma membrane calcium ATPase isoform 2 (PMCA2) is highly expressed on the apical membrane of mammary epithelial cells during lactation, and is the predominant pump responsible for calcium transport into milk...

  5. Vers une meilleure comprehension des savoirs disciplinaires et curriculaires des enseignants ou Ie paradigme retrouve

    Directory of Open Access Journals (Sweden)

    Stephane Martineau

    1999-01-01

    Full Text Available eet article se veut essentieUement un travail de synthese sous la forme d 'une breve revue de litterature au sujet des savoirs disciplinaires et curriculaires en enseignement. Plus specifiquement, il vise a determiner queUes sont les principales conclusions qui se degagent de la lecture des recherches empiriques sur les savoirs disciplinaires et curriculaires des enseignants des ordres d'enseignement primaire et secondaire. Il propose donc une classification des differentes dimensions constitutives du rapport entre les savoirs disciplinaires et curriculaires et la pratique enseignante. Les resultats mis au jour permettent d 'une part, d'identifier les facteurs qui entrainent des differences dans les connaissances disciplinaires et curriculaires des enseignants et d'autre part, de mieux saisir comment ces connaissances de l'enseignant peuvent influencer en retour sa pratique.

  6. Allergene des Wiesenlieschgrases Phleum pratense als Stimulatoren des angeborenen Immunsystems

    OpenAIRE

    Röschmann, Kristina

    2009-01-01

    Heuschnupfen und Asthma zählen weltweit zu den häufigsten chronischen Erkrankungen. Etwa 20 % der Bevölkerung westlicher Industriestaaten und bis zu 40 % der atopischen Individuen weisen eine Gräserpollenallergie auf17;32;43;44. Sowohl aus medizinischer, als auch aus volkwirtschaftlicher Sicht besteht daher ein großes Interesse an der näheren Untersuchung der Gräserpollenallergie. Da respiratorische Epithelien den Ort des ersten Kontaktes mit Aeroallergenen darstellen, war es Ziel dieser Arbe...

  7. Dynamique des populations du foreur des tiges du cacaoyer ...

    African Journals Online (AJOL)

    SARAH

    30 nov. 2014 ... déprédateur dans la région du Haut-Sassandra, la deuxième plus grande région de production de cacao en. Côte d'ivoire. Méthodologie et résultats : L'étude a été réalisée de 2009 à 2013 dans les plantations villageoises de la région du Haut-Sassandra en Côte d'Ivoire. Les variations des taux d'attaques ...

  8. Analysis of human bone alkaline phosphatase isoforms: comparison of isoelectric focusing and ion-exchange high-performance liquid chromatography.

    Science.gov (United States)

    Sharp, Christopher A; Linder, Cecilia; Magnusson, Per

    2007-04-01

    Several isoforms of alkaline phosphatase (ALP) can be identified in human tissues and serum after separation by anion-exchange HPLC and isoelectric focusing (IEF). We purified four soluble bone ALP (BALP) isoforms (B/I, B1x, B1 and B2) from human SaOS-2 cells, determined their specific pI values by broad range IEF (pH 3.5-9.5), compared these with commercial preparations of bone, intestinal and liver ALPs and established the effects of neuraminidase and wheat germ lectin (WGA) on enzyme activity. Whilst the isoforms B1x (pI=4.48), B1 (pI=4.32) and B2 (pI=4.12) resolved as well-defined bands, B/I resolved as a complex (pI=4.85-6.84). Neuraminidase altered the migration of all BALP isoforms to pI=6.84 and abolished their binding to the anion-exchange matrix, but increased their enzymatic activities by 11-20%. WGA precipitated the BALP isoforms in IEF gels and the HPLC column and attenuated their enzymatic activities by 54-73%. IEF resolved the commercial BALP into 2 major bands (pI=4.41 and 4.55). Migration of BALP isoforms is similar in IEF and anion-exchange HPLC and dependent on sialic acid content. HPLC is preferable in smaller scale research applications where samples containing mixtures of BALP isoforms are analysed. Circulating liver ALP (pI=3.85) can be resolved from BALP by either method. IEF represents a simpler approach for routine purposes even though some overlapping of the isoforms may occur.

  9. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis (Novartis)

    2013-11-20

    Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

  10. Differntiation genetique des populations geographiques de ...

    African Journals Online (AJOL)

    Differntiation genetique des populations geographiques de Colletotrichum kahawae, agent pathogene responsable de l\\'anthracnose des baies du cafeier Arabica. B Manga, J V Fabre, D Bieysse, J A Mouen Bedimo, C Herail, D Berry. Abstract. No Abstract. Cameroon Journal of Agricultural Science Vol. 1 (2) 2005 pp.

  11. Le language des masques burkinabè

    African Journals Online (AJOL)

    hond

    2 juil. 2007 ... un faire transformateur cognitif devient un esprit qui a des fonctions hautement spirituelles, religieuses et aussi souvent esthétiques. Le langage et le discours des masques. Les masques sont un langage et un discours. Un langage est un système de communi- cation et d'expression. L'unité de base de ...

  12. Mycotrophie Et Connaissances Paysannes Des Essences ...

    African Journals Online (AJOL)

    Dacryodes edulis, Elaesis guineensis, Citrus sinensis, Citrus reticulata, Mangifera indica et Persea americana sont plus fréquentes dans les deux sites. La classification des paysans des essences fertilitaires est basée sur certains attributs fonctionnels tels que le système racinaire et la surface foliaire. La comparaison entre ...

  13. Identites et apprentissage des langues Camerounaises | Assob ...

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... L'étude analyse l'effet des identités multiples sur la motivation des apprenants. ... of multiples identities on learners' motivation and suggests approaches for a rational management ... That is why the study identifies them as key stakeholders whose implication may further ...

  14. Immunopositivity for histone macroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Francesca Rappa

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously.We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN and the phosphatase and tensin homolog (PTEN liver specific knock-out (KO mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry.Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p<0.01 in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2, when compared to steatosis (<2% of hepatocytes positive for either isoform. The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2.These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC.

  15. The effect of a period of intensive exercise on the isoform test to detect growth hormone doping in sports.

    Science.gov (United States)

    Voss, S C; Giraud, S; Alsayrafi, M; Bourdon, P C; Schumacher, Y O; Saugy, M; Robinson, N

    2013-08-01

    The major objective of this study was to investigate the effects of several days of intense exercise on growth hormone (hGH) testing using the World Anti-Doping Agencies hGH isoform differential immunoassays. Additionally the effects of circadian variation and exercise type on the isoform ratios were also investigated. 15 male athletes performed a simulated nine day cycling stage race. Blood samples were collected twice daily over a period of 15 days (stage race+three days before and after). hGH isoforms were analysed by the official WADA immunoassays (CMZ Assay GmbH). All measured isoform ratios were far below the WADA decision limits for an adverse analytical finding. Changes in the isoform ratios could not be clearly connected to circadian variation, exercise duration or intensity. The present study demonstrates that the hGH isoform ratios are not significantly affected by exercise or circadian variation. We demonstrated that heavy, long term exercise does not interfere with the decision limits for an adverse analytical finding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

  17. The Regulation of Nitric Oxide Synthase Isoform Expression in Mouse and Human Fallopian Tubes: Potential Insights for Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Junting Hu

    2014-12-01

    Full Text Available Nitric oxide (NO is highly unstable and has a half-life of seconds in buffer solutions. It is synthesized by NO-synthase (NOS, which has been found to exist in the following three isoforms: neuro nitric oxide synthase (nNOS, inducible nitric oxide synthase (iNOS, and endothelial nitric oxide synthase (eNOS. NOS activity is localized in the reproductive tracts of many species, although direct evidence for NOS isoforms in the Fallopian tubes of mice is still lacking. In the present study, we investigated the expression and regulation of NOS isoforms in the mouse and human Fallopian tubes during the estrous and menstrual cycles, respectively. We also measured isoform expression in humans with ectopic pregnancy and in mice treated with lipopolysaccharide (LPS. Our results confirmed the presence of different NOS isoforms in the mouse and human Fallopian tubes during different stages of the estrous and menstrual cycles and showed that iNOS expression increased in the Fallopian tubes of women with ectopic pregnancy and in LPS-treated mice. Elevated iNOS activity might influence ovulation, cilia beats, contractility, and embryo transportation in such a manner as to increase the risk of ectopic pregnancy. This study has provided morphological and molecular evidence that NOS isoforms are present and active in the human and mouse Fallopian tubes and suggests that iNOS might play an important role in both the reproductive cycle and infection-induced ectopic pregnancies.

  18. The schizophrenia-associated Kv11.1-3.1 isoform results in reduced current accumulation during repetitive brief depolarizations.

    Directory of Open Access Journals (Sweden)

    Juliane Heide

    Full Text Available Recent genome wide association studies identified a brain and primate specific isoform of a voltage-gated potassium channel, referred to as Kv11.1-3.1, which is significantly associated with schizophrenia. The 3.1 isoform replaces the first 102 amino acids of the most abundant isoform (referred to as Kv11.1-1A with six unique amino acids. Here we show that the Kv11.1-3.1 isoform has faster rates of channel deactivation but a slowing of the rates of inactivation compared to the Kv11.1-1A isoform. The Kv11.1-3.1 isoform also has a significant depolarizing shift in the voltage-dependence of steady-state inactivation. The consequence of the altered gating kinetics is that there is lower current accumulation for Kv11.1-3.1 expressing cells during repetitive action potential firing compared to Kv11.1-1A expressing cells, which in turn will result in longer lasting trains of action potentials. Increased expression of Kv11.1-3.1 channels in the brain of schizophrenia patients might therefore contribute to disorganized neuronal firing.

  19. Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

    Science.gov (United States)

    Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

    2016-03-31

    Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

  20. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration.

    Science.gov (United States)

    Fearnley, Gareth W; Bruns, Alexander F; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-04-24

    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response. © 2015. Published by The Company of Biologists Ltd.

  1. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2015-07-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response.

  2. Improved Mask Protected DES using RSA Algorithm

    Directory of Open Access Journals (Sweden)

    Asha Latha S.

    2016-01-01

    Full Text Available The data encryption standard is a pioneering and farsighted standard which helped to set a new paradigm for encryption standards. But now DES is considered to be insecure for some application. Asymmetric mask protected DES is an advanced encryption method for effectively protecting the advanced DES. There are still probabilities to improve its security. This paper propose a method, which introduce a RSA key generation scheme in mask protected DES instead of plain key, which result in enhancement in the security of present asymmetric mask protected DES. We further propose a Vedic mathematical method of RSA implementation which reduce the complexity of computation in RSA block thereby resulting in reduced delay (four timesthat improves the performance of overall system. The software implementation was performed using Xilinx 13.2 and Model-Sim was used for the simulation environment.

  3. La tuberculose des amygdales palatines

    Directory of Open Access Journals (Sweden)

    Oudidi Abdelatif

    2010-01-01

    Full Text Available INTRODUCTION:La localisation tuberculeuse des amygdales palatines est très rare même dans un pays d’endémie tuberculeuse. Le diagnostic peut être suspecté cliniquement dans un contexte évocateur, mais il ne peut être certifié qu’au stade histologique. PATIENTS ET METHODES:Cinq cas de tuberculose des amygdales palatine ont été diagnostiqués sur une période de 5 ans et inclus dans une étude rétrospective. Nous avons recensé trois hommes et deux femmes (âge moyen de 28 ans. La dysphagie haute était le maître symptôme. L’examen a objectivé une hypertrophie amygdalienne chez tous les patients avec des ulcérations chez trois d’entre eux. Une biopsie a été effectuée chez trois patients et une amygdalectomie a été réalisée chez les deux autres. L’étude anatomopathologique a posé le diagnostic chez tous les patients. Un traitement médical antituberculeux selon un régime court allant de 6 à 9 mois a été instauré. Dans tous les cas, l’évolution à long terme a été favorable avec un recul moyen de 13 mois. CONCLUSION: La tuberculose amygdalienne est rare. Son diagnostic repose essentiellement sur le résultat anatomopathologique de la biopsie où de l’amygdalectomie. L’évolution sous traitement anti-bacillaire est souvent favorable, la récidive est exceptionnelle.

  4. Analyste des politiques (h/f) | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le titulaire doit contribuer par son savoir et son savoir-faire à la planification stratégique et opérationnelle; produire des documents à la demande du Conseil des ... en rédigeant des propositions, des lignes directrices et des annexes, et en organisant des consultations du personnel et des conférences électroniques.

  5. Agent (h/f) - Santé des voyageurs et mieux-être | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Fixer des rendez-vous au nom des voyageurs et envoyer des rappels à ces derniers. Fournir aux nouveaux voyageurs des directives au sujet des formulaires de santé-voyage à remettre. Envoyer les ordonnances à la pharmacie et prendre les dispositions voulues relatives à la livraison des médicaments et des vaccins, ...

  6. Eff ect of vitamin E isoforms on the primary intention Eff ect of vitamin E isoforms on the primary intention skin wound healing of diabetic rats

    Directory of Open Access Journals (Sweden)

    Bijo Elsy

    2017-10-01

    Full Text Available Introduction: Impaired wound healing events is a common complication in diabetes. One of the effective nutritional antioxidant on skin wound healing is vitamin E which contains saturated tocopherol and unsaturated tocotrienol forms. This present study is designed to explore the effect of different vitamin E isoforms on stitched skin wound in both healthy and diabetic rats. Materials and Methods: Forty eight albino rats were divided into eight groups; healthy control, diabetic control, healthy treated (d-α-tocopherol, d-δ-TRF and co-administrated and diabetic treated (d-αtocopherol, d-δ-TRF and co-administrated. Diabetes was induced through single subcutaneous injection of alloxan at the dose of 100 mg/kg. Treated groups were administered d-a-tocopherol (200 mg/kg, d-δ-TRF (200 mg/kg and co-administration (100 mg/kg of these two compounds each orally and daily for three weeks. A horizontal skin incision was made on right mid-thigh region at 2.95 ± 0.17cm in length and wound was closed with an absorbable suture. Results: Histopathological and histomorphological results at the end of 3rd week revealed that the d-δ-TRF treated groups promote the regeneration and reorganization of epidermal and dermal components in healing of primary intention more effectively than the d-α-tocopherol and co-administrated groups. Conclusion: It is concluded that among different vitamin E isoforms the d-δ-TRF appears to be a more effective nutritional antioxidant on skin wound healing in both healthy and diabetics.

  7. Expression and Immunohistochemical Localisation of the G beta gamma activated and Calcineurin-inhibited Adenylyl Cyclase Isoforms in Rat Articular Chondrocytes

    International Nuclear Information System (INIS)

    Memon, I.; Khan, K.M.; Siddiqui, S.; Perveen, S.; Ishaq, M.

    2016-01-01

    Objective: To determine the expression and localisation of the Gβγ-activated adenylyl cyclase (AC) isoforms 2, 4, and 7 and calcineurin-inhibited AC isoform 9 in rat articular chondrocytes. Study Design: Experimental study. Place and Duration of Study: Jumma Research Laboratory and Histology Laboratory, The Aga Khan University, Karachi, from 2009 to 2011. Methodology: Fresh slices of articular cartilage were taken from various synovial joints of rats of different age groups. The expression of AC isoforms was determined by RT-PCR and immunohistochemistry was performed to localise these isoforms in articular chondrocytes. Tissue sections were processed for immunostaining with respective antibodies. The color was developed by diaminobenzidine. Results: All the studied AC isoforms were found to be differentially expressed in different zones of the rat articular cartilage. Generally, expression of all AC isoforms studied increased with age. The expression of the AC isoforms through PCR was almost consistent with the localisation of these isoforms by immunohistochemistry. Conclusion: These data add to the information about signalling cascades possibly involved in articular chondrocytes. Variable expression of AC isoforms 2, 4, 7, and 9 suggest a role for the signalling cascades regulated by the AC isoforms in articular chondrocytes. (author)

  8. APLICACIÓN DE REDES NEURONALES EN LA CLASIFICACIÓN DE ARCILLAS APLICAÇÃO DE REDES NEURONAIS NA CLASSIFICAÇÃO DE ARGILAS APPLICATION OF NEURAL NETWORKS IN CLASSIFICATION OF CLAYS

    Directory of Open Access Journals (Sweden)

    Jairo Gómez

    2012-06-01

    Full Text Available Las arcillas son la materia prima fundamental en la fabricación de productos para el sector constructor tales como baldosas, enchapes, pavimentos y ladrillos. Las pequeñas y medianas industrias ladrilleras por lo general utilizan arcillas de diverso origen mineralógico, clasificadas para formular sus mezclas con base en la experiencia del equipo de personas responsables de la producción; la incertidumbre asociada con este método causa que una parte de sus productos se rechacen después de fabricados, porque sus propiedades no cumplen las especificaciones técnicas. En este artículo se presenta una metodología basada en redes neuronales que permite clasificar, con base en sus propiedades, las arcillas que se van a usar para componer las pastas, con el propósito de disminuir la cantidad de producto rechazado. Se emplearon diversas topologías de red para la clasificación, lo cual permitió encontrar una capaz de predecir las muestras de entrenamiento y prueba con 97,79 % y 94,12 % de precisión, respectivamente.As argilas são a matéria prima fundamental na fabricação de produtos para o setor construtor tais como baldosas, revestimentos, pavimentos e tijolos. As pequenas e médias indústrias de tijolos geralmente utilizam argilas de diversa origem mineralógica, classificadas para formular suas misturas com base na experiência da equipe de pessoas responsáveis pela produção; a incerteza associada com este método causa que uma parte de seus produtos se rejeite depois de fabricados, porque suas propriedades não cumprem as especificações técnicas. Em este artigo apresenta-se uma metodologia baseada em redes neuronais que permite classificar, com base em suas propriedades, as argilas que se vão usar para compor as massas, com o propósito de diminuir a quantidade de produto rejeitado. Empregaram-se diversas topologias de rede para a classificação, o qual permitiu encontrar uma capaz de predizer as mostras de treinamento e

  9. Emisión Acústica y Redes Neuronales para Modelado y Caracterización del Proceso de Soldadura por Fricción Agitación

    Directory of Open Access Journals (Sweden)

    Emilio Jiménez Macías

    2013-10-01

    of the ANN, while the outputs of model include the welding parameters: tool rotation speed and travel speed, as well as the tool profile. A multilayer feed-forward ANN has been selected and trained, using different algorithms and network architectures. The parameters provided by the ANN constitute the model and the characterization of the FSW process; finally an analysis of the comparison between the measured and the calculated data is presented, validating the results. The model obtained can be used to develop the automatic control of the parameters of the FSW process, based on vibro-acoustic signals, which constitutes the following step in this research line. Palabras clave: Redes neuronales artificiales, análisis de señales, modelado, perceptrón multicapas, medición de vibraciones, soldadura por fricción agitación, Keywords: Artificial neural networks, signal analysis, modelling, multilayer perceptron, vibration measurement, friction stir welding

  10. Membrane fluidization by alcohols inhibits DesK-DesR signalling in Bacillus subtilis.

    Science.gov (United States)

    Vaňousová, Kateřina; Beranová, Jana; Fišer, Radovan; Jemioła-Rzemińska, Malgorzata; Matyska Lišková, Petra; Cybulski, Larisa; Strzałka, Kazimierz; Konopásek, Ivo

    2018-03-01

    After cold shock, the Bacillus subtilis desaturase Des introduces double bonds into the fatty acids of existing membrane phospholipids. The synthesis of Des is regulated exclusively by the two-component system DesK/DesR; DesK serves as a sensor of the state of the membrane and triggers Des synthesis after a decrease in membrane fluidity. The aim of our work is to investigate the biophysical changes in the membrane that are able to affect the DesK signalling state. Using linear alcohols (ethanol, propanol, butanol, hexanol, octanol) and benzyl alcohol, we were able to suppress Des synthesis after a temperature downshift. The changes in the biophysical properties of the membrane caused by alcohol addition were followed using membrane fluorescent probes and differential scanning calorimetry. We found that the membrane fluidization induced by alcohols was reflected in an increased hydration at the lipid-water interface. This is associated with a decrease in DesK activity. The addition of alcohol mimics a temperature increase, which can be measured isothermically by fluorescence anisotropy. The effect of alcohols on the membrane periphery is in line with the concept of the mechanism by which two hydrophilic motifs located at opposite ends of the transmembrane region of DesK, which work as a molecular caliper, sense temperature-dependent variations in membrane properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. TYPOLOGIE DES PRODUCTEURS DE POMME DE TERRE DANS ...

    African Journals Online (AJOL)

    bolique des 10T/ha en 1991 (Cf. Graphe n°2) et la hausse des rende- ments obtenue ... la culture primeur souffre d'handicaps spécifiques qui ne lui per- mettent que des .... moyenne annuelle, 88 298 tonnes des semences pour une valeur de.

  12. Gestionnaire - Division de l'administration des subventions | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Résumé des fonctions Le gestionnaire est chargé d'un portefeuille de projets en cours ... du Centre au personnel de la gestion des subventions, à la clientèle, aux collègues de la Direction générale des ... Administration et contrôle des projets.

  13. Connaissances et attitudes des manipulateurs radio du Togo sur l ...

    African Journals Online (AJOL)

    Objectif : Evaluer les connaissances et les attitudes des manipulateurs togolais sur l'irradiation médicale des grossesses. Matériels et Méthode : Etude transversale menée en Avril 2011 chez 72 manipulateurs de radiologie des structures sanitaires publiques et privées du Togo. Résultats : Le quart des manipulateurs ...

  14. Évaluation des émissions de gaz à effet de serre des filières de traitement et de valorisation des boues issues du traitement des eaux usées

    OpenAIRE

    Reverdy, A.L.; Pradel, M.

    2011-01-01

    / Ce rapport présente l'inventaire des différentes consommations énergétiques, en consommables et des GES pour chaque poste de traitement et de valorisation des boues issues du traitement des eaux usées.

  15. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

    International Nuclear Information System (INIS)

    Olsson, Eleonor; Lövgren, Kristina; Fernö, Mårten; Grabau, Dorthe; Borg, Åke; Hegardt, Cecilia; Honeth, Gabriella; Bendahl, Pär-Ola; Saal, Lao H; Gruvberger-Saal, Sofia; Ringnér, Markus; Vallon-Christersson, Johan; Jönsson, Göran; Holm, Karolina

    2011-01-01

    The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44 + /CD24 - phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to

  16. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

    Directory of Open Access Journals (Sweden)

    Vallon-Christersson Johan

    2011-09-01

    Full Text Available Abstract Background The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. Methods We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Results Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. Conclusions We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in

  17. ADAPTIVE CHANGES OF MYOSIN ISOFORMS IN RESPONSE TO LONG-TERM STRENGTH AND POWER TRAINING IN MIDDLE-AGED MEN

    Directory of Open Access Journals (Sweden)

    Raivo Puhke

    2006-06-01

    Full Text Available The purpose of the study was to examine the adaptive changes in myosin heavy chain (MHC and light chain (MLC isoforms in human vastus lateralis muscle caused by long-term strength and power training (54 weeks, approximately 3 times a week in untrained middle- aged men (16 in the training and 6 in the control group. Muscular MHC and MLC isoforms were determined by means of SDS-PAGE gel electrophoresis. During the training period, maximal anaerobic cycling power increased by 64 W (p < 0.001 and the maximal jumping height by 1.5 cm (p < 0. 05 in the training group, but no significant changes were found in the control group. However, the group by time effect was not significant. In the training group, the increase of the maximal jumping height correlated with the number of strength and power training sessions (r = 0.56; p < 0.05. The change of the proportion of MHC IIa isoform from 52.6 ± 12.2% to 59.4 ± 11.6% did not reach statistical significance (p = 0.070 for group by time; within training group p = 0.061 and neither did the change of the proportion of MHC IIx isoform from 18.1 ± 11.4% to 11.1 ± 9.1% (p = 0.104 for group by time; within training group p=0.032. The degree of change of MHC IIx isoform correlated with the amount of earlier recreational sports activity (r = 0.61; p < 0.05. In the training group, the changes of MLC1s isoform correlated negatively with the changes of MLC1f isoform (r = -0. 79; p < 0.05 as well as with the changes in maximal anaerobic cycling power (r = -0.81; p < 0.05, and positively with those of MHC I isoform (r = 0.81; p < 0.05. In conclusion, the long- term strength and power training ~3 times a week seemed to have only slight effects on fast MHC isoforms in the vastus lateralis muscle of untrained middle-aged men; the proportion of MHC IIa tended to increase and that of MHC IIx tended to decrease. No changes in MLC isoform profile could be shown

  18. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P; Chantelot, S; Moisson, N [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  19. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P.; Chantelot, S.; Moisson, N. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  20. À l’aube des dieux

    Directory of Open Access Journals (Sweden)

    Pascal Semonsut

    2011-03-01

    Full Text Available De l’avis même des préhistoriens, la Préhistoire assiste à la naissance du sentiment religieux. Cette religion des origines, quelle image en ont les Français ? Telle est la question que cet article aborde à partir de l’étude des manuels scolaires et des œuvres de fiction (littérature, cinéma et bande dessinée de la seconde moitié du XXe siècle. Si l’enseignement et la fiction n’accordent pas la même place à ce thème, en revanche tous deux font des préhistoriques des polythéistes adorant le soleil, construisant des mégalithes et prenant le plus grand soin de leurs morts. Ce mélange d’obscurantisme et de vraie spiritualité n’a qu’un but : montrer que notre espèce ne pouvait être que victorieuse dans ce combat qu’est l’humanisation.