Sample records for um novo algoritmo

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

    NASA Astrophysics Data System (ADS)

    Benazzouz, Omar

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

  2. Ultrasonic location system =

    NASA Astrophysics Data System (ADS)

    Albuquerque, Daniel Filipe

    Esta tese apresenta um sistema de localizacao baseado exclusivamente em ultrassons, nao necessitando de recorrer a qualquer outra tecnologia. Este sistema de localizacao foi concebido para poder operar em ambientes onde qualquer outra tecnologia nao pode ser utilizada ou o seu uso esta condicionado, como sao exemplo aplicacoes subaquaticas ou ambientes hospitalares. O sistema de localizacao proposto faz uso de uma rede de farois fixos permitindo que estacoes moveis se localizem. Devido a necessidade de transmissao de dados e medicao de distancias foi desenvolvido um pulso de ultrassons robusto a ecos que permite realizar ambas as tarefas com sucesso. O sistema de localizacao permite que as estacoes moveis se localizem escutando apenas a informacao em pulsos de ultrassons enviados pelos farois usando para tal um algoritmo baseado em diferencas de tempo de chegada. Desta forma a privacidade dos utilizadores e garantida e o sistema torna-se completamente independente do numero de utilizadores. Por forma a facilitar a implementacao da rede de farois apenas sera necessario determinar manualmente a posicao de alguns dos farois, designados por farois ancora. Estes irao permitir que os restantes farois, completamente autonomos, se possam localizar atraves de um algoritmo iterativo de localizacao baseado na minimizacao de uma funcao de custo. Para que este sistema possa funcionar como previsto sera necessario que os farois possam sincronizar os seus relogios e medir a distancia entre eles. Para tal, esta tese propoe um protocolo de sincronizacao de relogio que permite tambem obter as medidas de distancia entre os farois trocando somente tres mensagens de ultrassons. Adicionalmente, o sistema de localizacao permite que farois danificados possam ser substituidos sem comprometer a operabilidade da rede reduzindo a complexidade na manutencao. Para alem do mencionado, foi igualmente implementado um simulador de ultrassons para ambientes fechados, o qual provou ser bastante preciso e uma ferramenta de elevado valor para simular o comportamento do sistema de localizacao sobre condicoes controladas.

  3. Implementação de um algoritmo para a limpeza de mapas da RCFM

    NASA Astrophysics Data System (ADS)

    Souza, C. L.; Wuensche, C. A.

    2003-08-01

    A Radiação Cósmica de Fundo em Microondas (RCFM), descoberta por Penzias e Wilson em 1965, é uma das ferramentas mais poderosas para o estudo da cosmologia. Com a descoberta de flutuações de temperatura na RCFM, da ordem de uma parte em 105, pelo COBE (1992), uma nova era teve início. Nos últimos onze anos, diversos instrumentos fizeram novas medidas de alta precisão, refinando os resultados apresentados pelo COBE, culminando com os resultados recentes do satélite WMAP. A análise de dados da RCFM, especialmente no caso de experimentos com pequena cobertura do céu, apresenta uma série de dificuldades devido a emissões de contaminantes externos, tais como a emissão da Galáxia e de fontes pontuais, e de ruídos intrínsecos tanto ao sistema de detecção quanto à estratégia de observação do céu. Uma das soluções típicas para a filtragem de dados brutos de um experimento para medir flutuações de temperatura é aplicar um gabarito (template) e um filtro passa alta ao produzir mapas simplificados (sem considerar matrizes de correlação ou covariância). No caso de experimentos que utilizam detectores HEMT, essa combinação de filtros remove, satisfatoriamente, ruídos do tipo 1/f gerados pela instabilidade no ganho do detector acoplado ao movimento do instrumento, definido pela estratégia de observação. Entretanto, o sinal resultante medido, tanto em simulações quanto em séries temporais reais, sugere que parte do sinal cosmológico pode estar sendo removido junto com o ruído dos detectores. Este trabalho descreve as etapas para a produção de um mapa típico (simulado) e os testes preliminares de um algoritmo para remover ruídos do tipo 1/f introduzidos pela estratégia de observação sem prejudicar a qualidade do sinal cosmológico presente no mapa.

  4. Uma Comparação entre Técnicas de Propagação de Erros em Astrofísica: Monte Carlo x Bootstrap

    NASA Astrophysics Data System (ADS)

    Zabot, Alexandre; Baptista, Raymundo

    2005-07-01

    Neste trabalho é feito um estudo comparativo entre dois algoritmos numéricos usados para propagação de erros em dados experimentais. Um deles é conhecido por Método de Monte carlo e o outro por Método de Bootstrap. Recentemente, Dhullon & Watson argüiram que a aplicação do método de Monte Carlo introduz ruído nos dados, e propuseram então a utilização do Bootstrap como alternativa capaz de produzir resultados superiores. O objetivo deste trabalho é testar a validade dessa afirmação. As duas técnicas foram aplicadas a três problemas diferentes: o ajsute de modelos de emissão LTE simples e atmosfera estelar a espectros estelares observados e o ajuste de curvas de luz de eclipses de Variáveis Cataclísmicas para a detemrinação da distribuição radial de brilho dos seus discos de acréscimo. Os métodos foram testados quanto à sua robusteza, ou seja, a capacidade de prover resultados coerentes enre si. Além disso, as soluções dos métodos foram comparadas. Os resultados indicam que não existe evidência de superioridade de um métodos em relação ao outro.

  5. Elastoplasticidad anisotropa de metales en grandes deformaciones

    NASA Astrophysics Data System (ADS)

    Caminero Torija, Miguel Angel

    El objetivo de este trabajo es el desarrollo de modelos y algoritmos numericos que simulen el comportamiento del material bajo estas condiciones en el contexto de programas de elementos finitos, dando como resultado predicciones mas precisas de los procesos de conformado y deformacion plastica en general. Para lograr este objetivo se han desarrollado diversas tareas destinadas a mejorar las predicciones en tres aspectos fundamentales. El primer aspecto consiste en la mejora de la descripcion del endurecimiento cinematico anisotropo en pequenas deformaciones, lo cual se ha realizado a traves de modelos y algoritmos implicitos de superficies multiples. Ha sido estudiada la consistencia de este tipo de modelos tanto si estan basados en una regla implicita similar a la de Mroz o en la regla de Prager. Ademas se han simulado los ensayos de Lamba y Sidebottom, obteniendo, en contra de la creencia general, muy buenas predicciones con la regla de Prager. Dichos modelos podrian ser extendidos de forma relativamente facil para considerar grandes deformaciones a traves de procedimientos en deformaciones logaritmicas, similares a los desarrollados en esta tesis y detallados a continuacion. El segundo aspecto consiste en la descripcion de la anisotropia elastoplastica inicial. Esto se ha conseguido mediante el desarrollo de modelos y algoritmos para plasticidad anisotropa en grandes deformaciones, bien ignorando la posible anisotropia elastica, bien considerandola simultaneamente con la anisotropia plastica. Para ello ha sido necesario desarrollar primero un nuevo algoritmo de elastoplasticidad anisotropa en pequenas deformaciones consistentemente linealizado y sin despreciar ningun termino, de tal forma que se conserve la convergencia cuadratica de los metodos de Newton. Este algoritmo en pequenas deformaciones ha servido para realizar la correccion plastica de dos algoritmos en grandes deformaciones. El primero de estos algoritmos es una variacion del clasico algoritmo de Eterovic y Bathe para incluir la posibilidad de plasticidad anisotropa con endurecimiento mixto. Este primer algoritmo esta restringido a casos de isotropia elastica. La isotropia elastica es una hipotesis bastante habitual en plasticidad anisotropa y tiene la ventaja de que permite el uso de formulaciones mixtas u/p. El segundo algoritmo, mas complejo y general, incluye la posibilidad de elasticidad anisotropa, plasticidad anisotropa y endurecimiento mixto. Este algoritmo supone una contribucion importante ya que esta basado en hipotesis comunmente aceptadas y utilizadas en elastoplasticidad isotropa: descomposicion multiplicativa del gradiente de deformaciones en parte elastica y parte plastica, descripcion hiperelastica sencilla en funcion de deformaciones logaritmicas e integracion exponencial que conserva el volumen. Ademas, la estructura final del algoritmo es modular y relativamente sencilla, consistiendo en un pre- y un postprocesador geometrico y una correccion plastica realizada en pequenas deformaciones. El algoritmo esta consistentemente linealizado para conservar la convergencia cuadratica asintotica de los metodos de Newton y la forma final que toma dicha linealizacion es similar al caso de isotropia elastoplastica implementado; consiste en el modulo tangente algoritmico de pequenas deformaciones sobre el que se aplica una transformacion para convertirlo en el de grandes deformaciones. Todos estos modelos han sido implementados en un codigo propio de elementos finitos denominado DULCINEA, el cual tiene formulaciones lagrangianas totales y actualizadas para grandes deformaciones. Una de las tareas necesarias para poder realizar las simulaciones, ha sido el estudio e implementacion de diferentes elementos que no sufran el bloqueo volumetrico severo que se observa en formulaciones estandar basadas en desplazamientos. Este bloqueo se debe a la condicion de quasi-incompresibilidad que imponen los modelos de plasticidad desviadores y consiste en una respuesta exageradamente rigida de la solucion obtenida por el metodo de los elementos finitos estandar. Entre los elementos implementados cabe destacar el basado en la formulacion mixta u/p, que contiene una interpolacion adicional de grados de libertad de presion. Estos grados de libertad adicionales habitualmente son internos al elemento en mecanica de solidos. En este trabajo se ha desarrollado e implementado en DULCINEA una familia de elementos tridimensionales mixtos en grandes deformaciones que incluye el caso particular BMIX 27/27/4, basado en la formulacion u/p, constituido por 27 nudos, con 27 puntos de integracion estandar y 4 grados de libertad de presiones, y que pasa la condicion Inf-Sup o de Babuska-Brezzi. Sin embargo, se ha observado que la formulacion u/p presenta ciertas limitaciones bajo las hipotesis conjuntas de anisotropia elastica y anisotropia plastica. (Abstract shortened by UMI.)

  6. Study and optimization of the macroscopic electrical response of carbon based nanocomposites for advanced applications

    NASA Astrophysics Data System (ADS)

    Silva, Jaime Pedro Oliveira da

    A presente tese centrou-se no estudo da resposta da constante dieletrica e condutividade eletrica em materiais compositos nos quais o reforco tinha uma elevada proporcao entre comprimento e diametro. O objeto de estudo foi o efeito de um reforco com uma elevada razao entre comprimento e diametro, concentracao e orientacao na resposta eletrica e dieletrica de um composito. Estes compositos tem uma grande importancia no desenvolvimento de materiais para sensores e atuadores. Num primeiro momento da dissertacao, explorou-se a resposta da constante dieletrica de um composito constituido por nanotubos de carbono como reforco e uma matriz polimerica. Verificou-se que um aumento da razao entre comprimento e diametro do reforco tem o efeito de aumentar a constante dieletrica do composito para uma igual fracao volumetrica de reforco. Constatou-se tambem que materiais na fase nematica demonstram uma constante dieletrica mais baixa quando comparados com materiais onde o reforco esta distribuido aleatoriamente. Ficou ainda demonstrado nesta dissertacao que materiais na fase nematica com razoes entre o comprimento e diametro diferentes a constante dieletrica segue uma lei de potencia. Numa segunda fase do trabalho, foi explorada a condutividade de nanocompositos polimericos reforcados com nanotubos de carbono, atraves de um modelo baseado em cilindros impenetraveis. Ficou demonstrado que o modelo e apropriado para descrever a condutividade eletrica de um nanocomposito polimerico reforcado com nanotubos. As simulacoes desenvolvidas demonstram que, aumentando a razao entre o comprimento e o diametro dos nanotubos de carbono, aumenta a condutividade eletrica do nanocomposito. No entanto, verifica-se que aumentando a anisotropia diminui a condutividade, sendo este efeito mais evidente para fracoes volumetricas maiores. Nesta dissertacao comprovou-se ainda que uma microestrutura gerada por um algoritmo de empacotamento sequencial pode ser descrita por um grafo aleatorio e que a condutividade num composito reforcado com nanofibras de carbono pode ser descrito por uma rede de Bethe. Atraves do uso da teoria das redes complexas, chegou-se a uma expressao para o limite de percolacao e, do mesmo modo, demonstrou-se que “hopping” entre fibras adjacentes resulta numa expressao que corresponde a um regime de desordem fraca. No trabalho desenvolvido tambem foi calculado os expoentes criticos, atraves da teoria das redes, para um sistema 3D composto por cilindros impenetraveis com uma interacao de curto alcance, demonstrando que os expoentes criticos estao relacionados por uma relacao de hiperescala comum para 3D e nao pertencem a mesma classe de universalidade como a percolacao numa rede. A aplicacao do modelo desenvolvido a compositos de epoxy reforcada, com diferentes metodos de dispersao de nanofibras de carbono, revelou que os metodos de dispersao usados para preparar os compositos tem uma forte influencia nas propriedades eletricas que podem ser capturadas pelo modelo. Neste contexto, ficou ainda demonstrado que a condutividade eletrica pode ser descrita por um regime de desordem fraca, isto ´e, um regime onde todas as conexoes fibra-fibra participam na condutividade do composito. O modelo desenvolvido foi aplicado igualmente a compositos de poly (vinylidene fluoride) reforcado com nanotubos de carbono com diferentes tratamentos de termicos de oxidacao. Verificou-se que os tratamentos de superficie aumentam o limite de percolacao e diminuem a condutividade. Nesta dissertacao provamos ainda que a condutividade do composito pode ser atribuida a um mecanismo de “hopping”, fortemente afetado pelos tratamentos de superficie dos reforcos.

  7. M S MOLECULARES Rumo aos limites da miniaturiza o - (Molecular Magnets - towards the limits of miniaturization)

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

    Reis, Mario S; Moreira Dos Santos, Antonio F

    Por s culos, acreditou-se que o magnetismo s se manifestava em metais, como aqueles contendo ferro; hoje, a imagem mais comum de um m talvez seja a daquelas plaquinhas flex veis coladas geladeira com propagandas dos mais diversos tipos. O leitor conseguiria imaginar um material puramente org nico daqueles que formam os seres vivos como magn tico? E m s do tamanho de mol culas? fato: ambos existem. Esses novos materiais, conhecidos como magnetos moleculares, descobertos e desenvolvidos em v rios laborat rios do mundo, j re nem longa lista de aplica es, do tratamento do c ncer a refrigeradoresmore » ecol gicos, passando pela transmiss o de eletricidade sem perda de calor e a fabrica o de computadores extremamente velozes.« less

  8. Thin films for gas sensors

    NASA Astrophysics Data System (ADS)

    Pires, Jose Miguel Alves Correia

    Nos ultimos anos tem-se assistido a um aumento dos investimentos na investigacao de novos materiais para aplicacao em sensores. Apesar de ja existir um bom numero de dispositivos explorados comercialmente, muitas vezes, quer devido aos elevados custos de producao, quer devido a uma crescente exigencia do ponto de vista das caracteristicas de funcionamento, continua a ser necessario procurar novos materiais ou novas formas de producao que permitam baixar os custos e melhorar o desempenho dos dispositivos. No campo dos sensores de gases tem-se verificado continuos avancos nos ultimos anos. Continua todavia a ser necessario conhecer melhor, tanto os processos de producao dos materiais, como os mecanismos que regulam a sensibilidade dos dispositivos aos gases, de modo a orientar adequadamente a investigacao dos novos materiais, nomeadamente no que se refere a optimizacao dos parâmetros que nao satisfazem ainda os requisitos do mercado. Um dos materiais que tem mostrado melhores qualidades para aplicacao em sensores de gases de tipo resistivo e o dioxido de estanho. Este material tem sido produzido sob diversas formas e usando diferentes tecnicas, como sejam: sol-gel [1], pulverizacao catodica (sputtering) por magnetrao [2-4], sinterizacao de pos [5, 6], ablacao laser [7] ou RGTO [8]. Os resultados obtidos revelam que as caracteristicas dos dispositivos sao muito dependentes das tecnicas usadas na sua producao. A deposicao usando sputtering reactivo por magnetrao e uma tecnica que permite obter filmes finos de oxido de estanho com diferentes caracteristicas, quer do ponto de vista da estrutura, quer da composicao, e por isso, tambem, com diferentes sensibilidades aos gases. No âmbito deste trabalho, foram produzidos filmes de SnO2 usando sputtering DC reactivo com diferentes condicoes de deposicao. Os substratos usados foram lâminas de vidro e o alvo foi estanho com 99.9% de pureza. Foi estudada a influencia da atmosfera de deposicao, da pressao parcial do O2, da temperatura do substrato e da potencia da descarga na estrutura do material depositado. Durante a deposicao, alem dos parâmetros ja referidos, foram tambem registados a pressao de base antes da entrada dos gases de sputtering, os fluxos de oxigenio e argon durante a deposicao, a distância alvo-substrato, o tempo de deposicao, a corrente e a tensao aplicadas ao magnetrao. Foram feitas algumas experiencias usando uma fonte RF, para comparacao. (Abstract shortened by ProQuest.).

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

    NASA Astrophysics Data System (ADS)

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

    2003-08-01

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

  10. Application of Sampling Based Model Predictive Control to an Autonomous Underwater Vehicle

    DTIC Science & Technology

    2010-07-01

    lineales y evita el mínimo local, el cual puede ocasionar que un vehículo quede inmóvil detrás de los obstáculos. El algoritmo SBMPC se aplica a un UAV...en un ambiente cargado de reflexiones de onda y a un UAV en un problema de mínimo común local. El algoritmo es luego usado en un modelo cinemático...tareas difíciles en ambientes atiborrados de reflexiones de onda tales como muelles y puertos. Sin embargo, dado que los UUVs tienen dinámicas áltamente

  11. Unificando los criterios de sepsis neonatal tardía: propuesta de un algoritmo de vigilancia diagnóstica

    PubMed Central

    Zea-Vera, Alonso; Turin, Christie G.; Ochoa, Theresa J.

    2015-01-01

    Las infecciones constituyen una de las principales causas de muerte en el periodo neonatal. El diagnóstico de sepsis neonatal representa un gran desafío ya que los recién nacidos presentan signos clínicos muy inespecíficos y los exámenes auxiliares tienen una baja sensibilidad. Con el objetivo de mejorar el diagnóstico correcto de esta patología proponemos un algoritmo de vigilancia diagnóstica para sepsis neonatal tardía en el Perú y países de la región. El algoritmo permite clasificar a los episodios como sepsis confirmada, probable o posible, y sobretodo busca identificar aquellos episodios que no corresponden a sepsis, evitando calificar otras patologías como “sepsis”. Un mejor diagnóstico permitiría tener tasas más reales de sepsis neonatal, mejorar el uso de antibióticos y evitar sus efectos negativos en el recién nacido, así como una visión más exacta de su impacto en la salud pública. PMID:25123879

  12. Evaluation of thermochemical biomass conversion in fluidized bed =

    NASA Astrophysics Data System (ADS)

    Neves, Daniel dos Santos Felix das

    Dado o aumento acelerado dos precos dos combustiveis fosseis e as incertezas quanto a sua disponibilidade futura, tem surgido um novo interesse nas tecnologias da biomassa aplicadas a producao de calor, eletricidade ou combustiveis sinteticos. Nao obstante, para a conversao termoquimica de uma particula de biomassa solida concorrem fenomenos bastante complexos que levam, em primeiro lugar, a secagem do combustivel, depois a pirolise e finalmente a combustao ou gasificacao propriamente ditas. Uma descricao relativamente incompleta de alguns desses estagios de conversao constitui ainda um obstaculo ao desenvolvimento das tecnologias que importa ultrapassar. Em particular, a presenca de elevados conteudos de materia volatil na biomassa poe em evidencia o interesse pratico do estudo da pirolise. A importância da pirolise durante a combustao de biomassa foi evidenciada neste trabalho atraves de ensaios realizados num reator piloto de leito fluidizado borbulhante. Verificou-se que o processo ocorre em grande parte a superficie do leito com chamas de difusao devido a libertacao de volateis, o que dificulta o controlo da temperatura do reator acima do leito. No caso da gasificacao de biomassa a pirolise pode inclusivamente determinar a eficiencia quimica do processo. Isso foi mostrado neste trabalho durante ensaios de gasificacao num reator de leito fluidizado de 2MWth, onde um novo metodo de medicao permitiu fechar o balanco de massa ao gasificador e monitorizar o grau de conversao da biomassa. A partir destes resultados tornou-se clara a necessidade de descrever adequadamente a pirolise de biomassa com vista ao projeto e controlo dos processos. Em aplicacoes de engenharia ha particular interesse na estequiometria e propriedades dos principais produtos piroliticos. Neste trabalho procurou-se responder a esta necessidade, inicialmente atraves da estruturacao de dados bibliograficos sobre rendimentos de carbonizado, liquidos piroliticos e gases, assim como composicoes elementares e poderes calorificos. O resultado traduziu-se num conjunto de parâmetros empiricos de interesse pratico que permitiram elucidar o comportamento geral da pirolise de biomassa numa gama ampla de condicoes operatorias. Para alem disso, propos-se um modelo empirico para a composicao dos volateis que pode ser integrado em modelos compreensivos de reatores desde que os parâmetros usados sejam adequados ao combustivel ensaiado. Esta abordagem despoletou um conjunto de ensaios de pirolise com varias biomassas, lenhina e celulose, e temperaturas entre os 600 e 975ºC. Elevadas taxas de aquecimento do combustivel foram alcancadas em reatores laboratoriais de leito fluidizado borbulhante e leito fixo, ao passo que um sistema termo-gravimetrico permitiu estudar o efeito de taxas de aquecimento mais baixas. Os resultados mostram que, em condicoes tipicas de processos de combustao e gasificacao, a quantidade de volateis libertada da biomassa e pouco influenciada pela temperatura do reator mas varia bastante entre combustiveis. Uma analise mais aprofundada deste assunto permitiu mostrar que o rendimento de carbonizado esta intimamente relacionado com o racio O/C do combustivel original, sendo proposto um modelo simples para descrever esta relacao. Embora a quantidade total de volateis libertada seja estabelecida pela composicao da biomassa, a respetiva composicao quimica depende bastante da temperatura do reator. Rendimentos de especies condensaveis (agua e especies orgânicas), CO2 e hidrocarbonetos leves descrevem um maximo relativamente a temperatura para dar lugar a CO e H2 as temperaturas mais altas. Nao obstante, em certas gamas de temperatura, os rendimentos de algumas das principais especies gasosas (e.g. CO, H2, CH4) estao bem correlacionados entre si, o que permitiu desenvolver modelos empiricos que minimizam o efeito das condicoes operatorias e, ao mesmo tempo, realcam o efeito do combustivel na composicao do gas. Em suma, os ensaios de pirolise realizados neste trabalho permitiram constatar que a estequiometria da pirolise de biomassa se relaciona de varias formas com a composicao elementar do combustivel original o que levanta varias possibilidades para a avaliacao e projeto de processos de combustao e gasificacao de biomassa.

  13. Analysis of the stability of housekeeping gene expression in the left cardiac ventricle of rats submitted to chronic intermittent hypoxia.

    PubMed

    Julian, Guilherme Silva; Oliveira, Renato Watanabe de; Tufik, Sergio; Chagas, Jair Ribeiro

    2016-01-01

    Obstructive sleep apnea (OSA) has been associated with oxidative stress and various cardiovascular consequences, such as increased cardiovascular disease risk. Quantitative real-time PCR is frequently employed to assess changes in gene expression in experimental models. In this study, we analyzed the effects of chronic intermittent hypoxia (an experimental model of OSA) on housekeeping gene expression in the left cardiac ventricle of rats. Analyses via four different approaches-use of the geNorm, BestKeeper, and NormFinder algorithms; and 2-ΔCt (threshold cycle) data analysis-produced similar results: all genes were found to be suitable for use, glyceraldehyde-3-phosphate dehydrogenase and 18S being classified as the most and the least stable, respectively. The use of more than one housekeeping gene is strongly advised. RESUMO A apneia obstrutiva do sono (AOS) tem sido associada ao estresse oxidativo e a várias consequências cardiovasculares, tais como risco aumentado de doença cardiovascular. A PCR quantitativa em tempo real é frequentemente empregada para avaliar alterações na expressão gênica em modelos experimentais. Neste estudo, analisamos os efeitos da hipóxia intermitente crônica (um modelo experimental de AOS) na expressão de genes de referência no ventrículo cardíaco esquerdo de ratos. Análises a partir de quatro abordagens - uso dos algoritmos geNorm, BestKeeper e NormFinder e análise de dados 2-ΔCt (ciclo limiar) - produziram resultados semelhantes: todos os genes mostraram-se adequados para uso, sendo que gliceraldeído-3-fosfato desidrogenase e 18S foram classificados como o mais e o menos estável, respectivamente. A utilização de mais de um gene de referência é altamente recomendada.

  14. Detección automática de NEOs en imágenes CCD utilizando la transformada de Hough

    NASA Astrophysics Data System (ADS)

    Ruétalo, M.; Tancredi, G.

    El interés y la dedicación por los objetos que se acercan a la órbita de la Tierra (NEOs) ha aumentado considerablemente en los últimos años, tanto que se han iniciado varias campañas de búsqueda sistemática para aumentar la población identificada de éstos. El uso de placas fotográficas e identificación visual está siendo sustituído, progresivamente, por el uso de cámaras CCD y paquetes de detección automática de los objetos en las imágenes digitales. Una parte muy importante para la implementación exitosa de un programa automatizado de detección de este tipo es el desarrollo de algoritmos capaces de identificar objetos de baja relación señal-ruido y con requerimientos computacionales no elevados. En el presente trabajo proponemos la utilización de la transformada de Hough (utilizada en algunas áreas de visión artificial) para detectar automáticamente trazas, aproximadamente rectilíneas y de baja relación señal-ruido, en imágenes CCD. Desarrollamos una primera implementación de un algoritmo basado en ésta y lo probamos con una serie de imágenes reales conteniendo trazas con picos de señales de entre ~1 σ y ~3 σ por encima del nivel del ruido de fondo. El algoritmo detecta, sin inconvenientes, la mayoría de los casos y en tiempos razonablemente adecuados.

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

    Cripps, C.

    De novo biosynthesis of linoleic acid was demonstrated in vivo in 8 of 32 insect species examined, including both holometabolous and hemimetabolous species. The incorporation of (1-{sup 14}C) acetate into linoleic acid was demonstrated by radio-gas-liquid chromatography (radio-GLC), and in selected species by radio-high-performance liquid chromatography, silver nitrate thin-layer chromatography, radio-GLC and GLC linked to mass spectrometry of ozonolysis products. Analysis of the ozonolysis products clearly demonstrated that the entire molecule was labeled and that synthesis of linoleate was de novo from acetate. The in vivo incorporation of (1-{sup 14}C)acetate into lipid was monitored during the final three stadia ofmore » both male and female house crickets, Acheta domesticus. Characterization of the {Delta}{sup 12}-desaturase showed that, in the house cricket, this enzyme is microsomal and requires a reduced pyridine dinucleotide as a cofactor, with NADPH the preferred electron donor. The optimal substrate concentration for desaturation is about 40 uM. Addition of the microsomal supernatant, MgCl{sub 2} or ATP did not enhance activity. The form of the substrate for the desaturase, oleic acid, was determined and appears to be a CoA derivative, as is true for most animal desaturases, rather than a complex lipid, as it is in plants.« less

  16. Ondas de choque em jatos de quasares e objetos BL Lacertae

    NASA Astrophysics Data System (ADS)

    Melo, F. E.; Botti, L. C. L.

    2003-08-01

    Este trabalho é parte de um projeto que vem sendo realizado há dois anos no CRAAM, cujos objetivos principais são analisar e aplicar um modelo generalizado de ondas de choque em jatos relativísticos de plasma, presentes em quasares e objetos BL Lacertae, para explicar a variabilidade observada nestes objetos. O método consiste em uma decomposição de curvas de luz em séries de explosões similares, em várias freqüências, baseando-se em uma evolução espectro-temporal média das explosões. A partir da evolução média, um ajuste de cada explosão é feito com base em equações empíricas, modificando-se apenas parâmetros específicos de cada explosão. Inicialmente o modelo foi aplicado ajustando-se as curvas de luz a explosões delineadas por uma evolução do choque em três estágios, segundo a predominância do processo de emissão: síncrotron, Compton e adiabático. Entretanto, nesta nova fase de projeto, visando uma parametrização mais concisa, uma otimização do algoritmo de ajuste e uma convergência mais rápida, a formulação para cada evento foi assumida com uma evolução em apenas dois estágios: subida e descida. Isto possibilitou uma ótima delineação das curvas de luz das fontes OV236, OJ287, 3C273 e BL Lac, entre 1980 e 2000, nas freqüências 4.8, 8.0, 14.5 e 22 GHz, utilizando-se dados do Observatório da Universidade de Michigan, do Observatório do Itapetinga (Atibaia SP) e do Observatório Metsähovi. Como conclusões importantes, verificou-se que: os parâmetros ajustados descrevem o comportamento do jato; os valores do índice que descreve a expansão do jato sugerem que o mesmo se expande de uma forma não-cônica; o campo magnético é turbulento atrás da frente de choque; e as peculiaridades das explosões são devidas à influência de grandezas tais como o coeficiente da distribuição espectral de energia dos elétrons, a intensidade de campo magnético e o fator de feixe Doppler, no início do choque.

  17. Novel materials based on chitosan, its derivatives and cellulose fibres

    NASA Astrophysics Data System (ADS)

    Fernandes, Susana Cristina de Matos

    O presente trabalho tem como principal objectivo o desenvolvimento de novos materiais baseados em quitosano, seus derivados e celulose, na forma de nanofibras ou de papel. Em primeiro lugar procedeu-se a purificacao das amostras comerciais de quitosano e a sua caracterizacao exaustiva em termos morfologicos e fisicoquimicos. Devido a valores contraditorios encontrados na literatura relativamente a energia de superficie do quitosano, e tendo em conta a sua utilizacao como precursor de modificacoes quimicas e a sua aplicacao em misturas com outros materiais, realizou-se tambem um estudo sistematico da determinacao da energia de superficie do quitosano, da quitina e seus respectivos homologos monomericos, por medicao de ângulos de contacto Em todas as amostras comerciais destes polimeros identificaram-se impurezas nao polares que estao associadas a erros na determinacao da componente polar da energia de superficie. Apos a remocao destas impurezas, o valor da energia total de superficie (gs), e em particular da sua componente polar, aumentou consideravelmente. Depois de purificadas e caracterizadas, algumas das amostras de quitosano foram entao usadas na preparacao de filmes nanocompositos, nomeadamente dois quitosanos com diferentes graus de polimerizacao, correspondentes derivados soluveis em agua (cloreto de N-(3-(N,N,N-trimetilamonio)-2- hidroxipropilo) de quitosano) e nanofibras de celulose como reforco (celulose nanofibrilada (NFC) e celulose bacteriana (BC). Estes filmes transparentes foram preparados atraves de um processo simples e com conotacao 'verde' pela dispersao homogenea de diferentes teores de NFC (ate 60%) e BC (ate 40%) nas solucoes de quitosano (1.5% w/v) seguida da evaporacao do solvente. Os filmes obtidos foram depois caracterizados por diversas tecnicas, tais como SEM, AFM, difraccao de raio-X, TGA, DMA, ensaios de traccao e espectroscopia no visivel. Estes filmes sao altamente transparentes e apresentam melhores propriedades mecânicas e maior estabilidade termica do que os correspondentes filmes sem reforco. Outra abordagem deste trabalho envolveu o revestimento de folhas de papel de E. globulus com quitosano e dois derivados, um derivado fluorescente e um derivado soluvel em agua, numa maquina de revestimentos ('maquina de colagem') a escala piloto. Este estudo envolveu inicialmente a deposicao de 1 a 5 camadas do derivado de quitosano fluorescente sobre as folhas de papel de forma a estudar a sua distribuicao nas folhas em termos de espalhamento e penetracao, atraves de medicoes de reflectância e luminescencia. Os resultados mostraram que, por um lado, a distribuicao do quitosano na superficie era homogenea e que, por outro lado, a sua penetracao atraves dos poros do papel cessou apos tres deposicoes. Depois da terceira camada verificou-se a formacao de um filme continuo de quitosano sobre a superficie do papel. Estes resultados mostram que este derivado de quitosano fluorescente pode ser utilizado como marcador na optimizacao e compreensao de mecanismos de deposicao de quitosano em papel e outros substratos. Depois de conhecida a distribuicao do quitosano nas folhas de papel, estudou-se o efeito do revestimento de quitosano e do seu derivado soluvel em agua nas propriedades finais do papel. As propriedades morfologicas, mecânicas, superficiais, opticas, assim como a permeabilidade ao ar e ao vapor de agua, a aptidao a impressao e o envelhecimento do papel, foram exaustivamente avaliadas. De uma forma geral, os revestimentos com quitosano e com o seu derivado soluvel em agua tiveram um impacto positivo nas propriedades finais do papel, que se mostrou ser dependente do numero de camadas depositadas. Os resultados tambem mostraram que os papeis revestidos com o derivado soluvel em agua apresentaram melhores propriedades opticas, aptidao a impressao e melhores resultados em relacao ao envelhecimento do que os papeis revestidos com quitosano. Assim, o uso de derivados de quitosano soluveis em agua em processos de revestimento de papel representa uma estrategia bastante interessante e sustentavel para o desenvolvimento de novos materiais funcionais ou na melhoria das propriedades finais dos papeis. Por fim, tendo como objectivo valorizar os residuos e fraccoes menos nobres da quitina e do quitosano provenientes da industria transformadora, estes polimeros foram convertidos em poliois viscosos atraves de uma reaccao simples de oxipropilacao. Este processo tem tambem conotacao "verde" uma vez que nao requer solvente, nao origina subprodutos e nao exige nenhuma operacao especifica (separacao, purificacao, etc) para isolar o produto da reaccao. As amostras de quitina e quitosano foram pre-activadas com KOH e depois modificadas com um excesso de oxido de propileno (PO) num reactor apropriado. Em todos os casos, o produto da reaccao foi um liquido viscoso composto por quitina ou quitosano oxipropilados e homopolimero de PO. Estas duas fraccoes foram separadas e caracterizadas.

  18. Child Development: New Diagnoses for the NANDA International.

    PubMed

    Souza, Juliana Martins de; Cruz, Diná de Almeida Lopes Monteiro da; Veríssimo, Maria De La Ó Ramallo

    2018-04-01

    The paper proposes new diagnoses on child development (CD) for NANDA International. The study followed the recommended steps of Developmental Processes for NANDA International Nursing Diagnoses. It was a secondary analysis study on the findings of a concept analysis study on CD. A proposal of labels and components of three diagnoses: "Delayed child development," "Risk for delayed child development," and "Readiness for enhanced child development." The proposed diagnoses represent all the complexity of CD. The proposed diagnoses can support nurses in the development of a comprehensive care plan on the health of children. OBJETIVO: propor novos diagnósticos de enfermagem para a NANDA-International que abordem o desenvolvimento infantil. MÉTODO: Este estudo seguiu as etapas recomendadas para o desenvolvimento de diagnósticos de enfermagem da NANDA-International. Foi realizado a partir dos resultados da análise de conceito do termo desenvolvimento infantil. Propostos os títulos e os componentes de três diagnósticos: "Atraso no desenvolvimento infantil," "Risco de atraso no desenvolvimento infantil," e "Disposição para desenvolvimento infantil melhorado." CONCLUSÕES: Os diagnósticos propostos contemplam toda a complexidade do desenvolvimento infantil. IMPLICAÇÕES PARA A PRÁTICA DE ENFERMAGEM: Os novos diagnósticos podem subsidiar o enfermeiro na elaboração de um plano de cuidados integrais à saúde da criança. © 2016 NANDA International, Inc.

  19. Determinação de elementos próprios dos asteróides troianos: comparação entre as teorias semi-analítica e sintética

    NASA Astrophysics Data System (ADS)

    Roig, F.; Beaugé, C.

    2003-08-01

    Além do cálculo semi-analítico de elementos próprios dos asteróides Troianos (Beaugé & Roig 2001, Icarus 153, 391), recentemente foi apresentado um novo conjunto destes elementos próprios determinado através de uma teoria sintética (Knenezevic & Milani 2003, comunicação pessoal). As bases de dados contendo estas determinações estão disponiveis na pagina web do Asteroid Dynamical Site (http://hamilton.dm.unipi.it/cgi-bin/astdys/astibo). Nesta comunicação apresentamos os primeiros resultados de um estudo comparativo entre ambos conjuntos de elementos próprios, analisando suas vantagens e desvantagens, assim como os limites de precisão de cada conjunto. Mostramos que os elementos próprios sintéticos são mais precisos que os smi-analíticos para grandes amplitudes de libração do ângulo s = l-lJup, embora acontece o contrario para os corpos cuja amplitude de libração é muito pequena. Finalmente discutimos a influencia destes erros na determinação de familias de asteroides e da estrutura resonante em torno dos pontos Lagrangeanos L4 e L5.

  20. Detecção da fase impulsiva de uma explosão solar gigante até 405 GHz

    NASA Astrophysics Data System (ADS)

    Raulin, J.-P.; Makhmutov, V.; Kaufmann, P.; Pacini, A. A.; Luethi, T.; Hudson, H. S.; Gary, D. E.; Yoshimori, M.

    2003-08-01

    A explosão ocorrida no dia 25/08/2001 foi uma das mais intensas do presente ciclo solar em ondas de rádio de altas frequências. Foram medidas em ondas milimétricas e submilimétricas, aproximadamente, 105 e vários milhares de unidades de fluxo solar, respectivamente. Apresentamos um estudo deste evento em múltiplas frequências, desde microondas (1GHz), até ondas submilimétricas (405 GHz) detectadas pelo Telescópio Solar para ondas Submilimétricas (SST). Esta base de dados foi complementada utilizando-se o experimento Yohkoh, incluindo a emissão em raios-X duros e raios-g (até 100 MeV), e imagens em raios-X moles da região ativa envolvida. Enfocamos e discutimos principalmente os seguintes aspectos da fase impulsiva do evento: (i) as implicações deduzidas do espectro eletromagnético, obtido pela primeira vez até 405 GHz; (ii) a dinâmica da região ativa. Os resultados mostram que para explicar o espectro rádio observado, são necessários entre 3.5×1037 e 1.5×1039 elétrons acelerados acima de 20 keV em uma região de campo magnético entre 300 e 800 Gauss. A estimativa do fluxo de fótons que seria produzido por estes elétrons, mostra que grande parte deles não precipitou na baixa atmosfera. A evolução temporal da emissão em raios-X moles revela que a configuração magnética da região ativa foi muito dinâmica durante a fase impulsiva da explosão. Em particular, mostramos que a produção dos elétrons altamente energéticos foi iniciada junto com a aparição, na baixa coroa solar, de um novo sistema compacto de estruturas magnéticas. Este fato sugere que os locais de aceleração estão localizados na baixa atmosfera do Sol, como resultado da interação entre o novo sistema compacto e o campo magnético ambiente da região ativa.

  1. MRUniNovo: an efficient tool for de novo peptide sequencing utilizing the hadoop distributed computing framework.

    PubMed

    Li, Chuang; Chen, Tao; He, Qiang; Zhu, Yunping; Li, Kenli

    2017-03-15

    Tandem mass spectrometry-based de novo peptide sequencing is a complex and time-consuming process. The current algorithms for de novo peptide sequencing cannot rapidly and thoroughly process large mass spectrometry datasets. In this paper, we propose MRUniNovo, a novel tool for parallel de novo peptide sequencing. MRUniNovo parallelizes UniNovo based on the Hadoop compute platform. Our experimental results demonstrate that MRUniNovo significantly reduces the computation time of de novo peptide sequencing without sacrificing the correctness and accuracy of the results, and thus can process very large datasets that UniNovo cannot. MRUniNovo is an open source software tool implemented in java. The source code and the parameter settings are available at http://bioinfo.hupo.org.cn/MRUniNovo/index.php. s131020002@hnu.edu.cn ; taochen1019@163.com. 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

  2. Toward Advanced Nursing Practice along with People-Centered Care Partnership Model for Sustainable Universal Health Coverage and Universal Access to Health.

    PubMed

    Kamei, Tomoko; Takahashi, Keiko; Omori, Junko; Arimori, Naoko; Hishinuma, Michiko; Asahara, Kiyomi; Shimpuku, Yoko; Ohashi, Kumiko; Tashiro, Junko

    2017-01-30

    this study developed a people-centered care (PCC) partnership model for the aging society to address the challenges of social changes affecting people's health and the new role of advanced practice nurses to sustain universal health coverage. a people-centered care partnership model was developed on the basis of qualitative meta-synthesis of the literature and assessment of 14 related projects. The ongoing projects resulted in individual and social transformation by improving community health literacy and behaviors using people-centered care and enhancing partnership between healthcare providers and community members through advanced practice nurses. people-centered care starts when community members and healthcare providers foreground health and social issues among community members and families. This model tackles these issues, creating new values concerning health and forming a social system that improves quality of life and social support to sustain universal health care through the process of building partnership with communities. a PCC partnership model addresses the challenges of social changes affecting general health and the new role of advanced practice nurses in sustaining UHC. o estudo desenvolveu um modelo de parceria de cuidados centrados nas pessoas (CCP) para uma sociedade que está envelhecendo, com o fim de enfrentar os desafios das mudanças sociais que afetam a saúde das pessoas e o novo papel da prática avançada de enfermagem para sustentar a cobertura universal de saúde. um modelo de parceria de cuidados centrados nas pessoas foi desenvolvido com base na meta-síntese qualitativa da literatura e a avaliação de 14 projetos relacionados. Os projetos em curso resultaram na transformação individual e social, melhorando a alfabetização de saúde da comunidade e comportamentos que usam o cuidado centrado nas pessoas e aumentando a parceria entre os profissionais de saúde e membros da comunidade por meio da prática avançada de enfermagem. o cuidado centrado nas pessoas começa quando os membros da comunidade e os profissionais de saúde colocam em primeiro plano as questões sociais entre os membros da comunidade e das famílias. Esse modelo aborda essas questões, a criação de novos valores relativos à saúde e forma um sistema social que melhora a qualidade de vida e dá apoio social para sustentar o sistema de saúde universal por meio da construção de parcerias com as comunidades. um modelo de parceria CCP aborda os desafios das mudanças sociais que afetam a saúde geral e o novo papel das enfermeiras de prática avançada em sustentar a UHC. este estudio desarrolló un modelo de alianza para el cuidado centrado en las personas (CCP) para una sociedad envejecida, que haga frente a los retos de los cambios sociales que afectan a la salud de las personas y el nuevo papel de las enfermeras de práctica avanzada para apoyar la cobertura universal de salud. un modelo de alianza para el cuidado centrado en las personas fue desarrollado sobre la base de la meta-síntesis cualitativa de la literatura y la evaluación de 14 proyectos relacionados. Los proyectos en curso dieron lugar a la transformación individual y social mejorando la "alfabetización sanitaria" de la comunidad y los comportamientos, utilizando los cuidados centrados en las personas y aumentando la colaboración entre los profesionales sanitarios y miembros de la comunidad a través de las enfermeras de práctica avanzada. el cuidado centrado en las personas comienza cuando los miembros de la comunidad y los profesionales sanitarios ponen en primer plano a la salud y las cuestiones sociales entre los miembros de la comunidad y las familias. Este modelo aborda estas cuestiones, creando nuevos valores relativos a la salud y formando un sistema social que mejora la calidad de vida y el apoyo social para hacer sostenible la atención sanitaria universal a través del proceso de construcción de alianzas con las comunidades. un modelo de alianza para CCP responde a los desafíos de los cambios sociales que afectan a la salud en general y al nuevo papel de las enfermeras de práctica avanzada en el sostenimiento de la Cobertura Universal en Salud (CUS).

  3. Open-pNovo: De Novo Peptide Sequencing with Thousands of Protein Modifications.

    PubMed

    Yang, Hao; Chi, Hao; Zhou, Wen-Jing; Zeng, Wen-Feng; He, Kun; Liu, Chao; Sun, Rui-Xiang; He, Si-Min

    2017-02-03

    De novo peptide sequencing has improved remarkably, but sequencing full-length peptides with unexpected modifications is still a challenging problem. Here we present an open de novo sequencing tool, Open-pNovo, for de novo sequencing of peptides with arbitrary types of modifications. Although the search space increases by ∼300 times, Open-pNovo is close to or even ∼10-times faster than the other three proposed algorithms. Furthermore, considering top-1 candidates on three MS/MS data sets, Open-pNovo can recall over 90% of the results obtained by any one traditional algorithm and report 5-87% more peptides, including 14-250% more modified peptides. On a high-quality simulated data set, ∼85% peptides with arbitrary modifications can be recalled by Open-pNovo, while hardly any results can be recalled by others. In summary, Open-pNovo is an excellent tool for open de novo sequencing and has great potential for discovering unexpected modifications in the real biological applications.

  4. Apparent Motion of the Sun, Shadows of Objects and Measurement of Time in the View of Seventh Grade Students of Middle School. (Breton Title: Movimento Aparente do Sol, Sombras dos Objetos e Medição do Tempo na Visão de Alunos do Sétimo Ano do Ensino Fundamental.) Movimiento Aparente del Sol, Sombras de los Objetos y Medición del Tiempo en la Visión de Estudiantes del Séptimo Grado del Ciclo Pirmario

    NASA Astrophysics Data System (ADS)

    Iria Machado, Daniel

    2013-07-01

    The apparent motion of the Sun on the celestial sphere and the behavior of the shadows of objects over time are observable phenomena in everyday life. However, students often do not have a proper understanding of such occurrences, and can even display misconceptions about them. Therefore, we performed a research in order to know students' notions about these subjects and to evaluate the contribution to their understanding brought about by an activity performed with an interactive sundial in an informal learning environment. We investigated the ideas of 43 students from the seventh grade of middle school by applying a test with open questions before and after an activity with an analemmatic sundial, conducted by a monitor. A significant proportion of students were initially unaware of most of the phenomena treated. The intervention performed helped the students to assimilate new concepts, providing the contact with new phenomena and to a lesser degree, the development of explanations about them, indicating an educational potential of this action. However, the contribution to the understanding of some of the ideas explored was small, pointing to the need to make additional observations, studies and discussions. O movimento aparente do Sol na esfera celeste e o comportamento das sombras dos objetos com o passar do tempo são fenômenos observáveis no dia a dia. No entanto, muitas vezes os estudantes não possuem uma compreensão adequada de tais ocorrências, podendo inclusive exibir concepções alternativas a seu respeito. Por isso, efetuou-se uma pesquisa com o intuito de conhecer as noções dos alunos sobre esses temas e avaliar a contribuição para seu entendimento propiciada por uma atividade feita com um relógio de Sol interativo, em um ambiente de ensino informal. Foram investigadas as ideias de 43 alunos do sétimo ano do Ensino Fundamental mediante a aplicação de um teste com questões abertas antes e depois de uma atividade com um relógio de Sol analemático, conduzida por um monitor. Uma proporção significativa de estudantes desconhecia inicialmente a maioria dos fenômenos tratados. A intervenção realizada colaborou para uma parte dos alunos assimilar novos conceitos, propiciando o contato com novos fenômenos e, em menor grau, a elaboração de explicações a respeito destes, indicando um potencial educativo dessa ação. Porém, a contribuição para o entendimento de algumas das ideias exploradas foi pequena, apontando para a necessidade de se fazer observações, estudos e discussões complementares. El movimiento aparente del Sol en la esfera celeste y el comportamiento de las sombras de los objetos a lo largo del tiempo son fenómenos observables en la vida cotidiana. Sin embargo, los estudiantes a menudo no tienen una adecuada comprensión de dichos problemas, e incluso pueden mostrar conceptos erróneos acerca de ellos. Por lo tanto, se realizó una investigación a fin de conocer las nociones de los estudiantes acerca de estas cuestiones y evaluar la contribución a su comprensión proporcionada por una actividad realizada con un reloj de Sol interactivo, en un entorno informal de aprendizaje. Se investigaron las ideas de 43 estudiantes del séptimo grado del ciclo primario mediante la aplicación de un test con preguntas abiertas antes y después de una actividad con un reloj de Sol analemático, dirigida por un monitor. Una proporción significativa de los estudiantes inicialmente desconocía la mayoría de los fenómenos tratados. La intervención realizada contribuyó para que los estudiantes asimilasen nuevos conceptos, proporcionando el contacto con nuevos fenómenos y, en menor medida, desarrollasen explicaciones acerca de estos, lo que indica un potencial educativo de esta acción. Sin embargo, la contribución a la comprensión de algunas de las ideas exploradas fue pequeña, lo que apunta a la necesidad de hacer observaciones, estudios y debates adicionales.

  5. UniNovo: a universal tool for de novo peptide sequencing.

    PubMed

    Jeong, Kyowon; Kim, Sangtae; Pevzner, Pavel A

    2013-08-15

    Mass spectrometry (MS) instruments and experimental protocols are rapidly advancing, but de novo peptide sequencing algorithms to analyze tandem mass (MS/MS) spectra are lagging behind. Although existing de novo sequencing tools perform well on certain types of spectra [e.g. Collision Induced Dissociation (CID) spectra of tryptic peptides], their performance often deteriorates on other types of spectra, such as Electron Transfer Dissociation (ETD), Higher-energy Collisional Dissociation (HCD) spectra or spectra of non-tryptic digests. Thus, rather than developing a new algorithm for each type of spectra, we develop a universal de novo sequencing algorithm called UniNovo that works well for all types of spectra or even for spectral pairs (e.g. CID/ETD spectral pairs). UniNovo uses an improved scoring function that captures the dependences between different ion types, where such dependencies are learned automatically using a modified offset frequency function. The performance of UniNovo is compared with PepNovo+, PEAKS and pNovo using various types of spectra. The results show that the performance of UniNovo is superior to other tools for ETD spectra and superior or comparable with others for CID and HCD spectra. UniNovo also estimates the probability that each reported reconstruction is correct, using simple statistics that are readily obtained from a small training dataset. We demonstrate that the estimation is accurate for all tested types of spectra (including CID, HCD, ETD, CID/ETD and HCD/ETD spectra of trypsin, LysC or AspN digested peptides). UniNovo is implemented in JAVA and tested on Windows, Ubuntu and OS X machines. UniNovo is available at http://proteomics.ucsd.edu/Software/UniNovo.html along with the manual.

  6. DeNovoGUI: An Open Source Graphical User Interface for de Novo Sequencing of Tandem Mass Spectra

    PubMed Central

    2013-01-01

    De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com. PMID:24295440

  7. DeNovoGUI: an open source graphical user interface for de novo sequencing of tandem mass spectra.

    PubMed

    Muth, Thilo; Weilnböck, Lisa; Rapp, Erdmann; Huber, Christian G; Martens, Lennart; Vaudel, Marc; Barsnes, Harald

    2014-02-07

    De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com .

  8. Observação do abrilhantamento de limbo solar e de estruturas filamentares em 48 ghz utilizando a técnica de regularização adaptativa

    NASA Astrophysics Data System (ADS)

    Machado, W. R. S.; Mascarenhas, N.; Costa, J. E. R.; Silva, A. V. R.

    2003-08-01

    O radiotelescópio do Itapetinga tem sido utilizado em campanhas de observações de explosões solares gerando um grande número de mapas diários em 48 GHz como sub-produto destas observações. A resolução espacial do telescópio de 14m do Itapetinga nesta freqüência é de aproximadamente dois minutos de arco. Estruturas de interesse para análise da atmosfera solar quiescente tais como os filamentos e o anel de abrilhantamento do limbo são de dimensão angular moderada da ordem ou ligeiramente menores que a resolução do telescópio. É conhecido que a convolução da função de espalhamento do telescópio, PSF (padrão de ganho do feixe) borra as estruturas de dimensão angular abaixo do HPBW (largura a meia potência do feixe) e portanto é comum a busca por técnicas de restauração que eliminem pelo menos em parte este borramento. Estudamos a restauração destas radioimagens usando a técnica de regularização adaptativa e os resultados ressaltam estas estruturas espaciais de pequeno contraste. O algoritmo da regularização adaptativa faz uso de k imagens, chamadas protótipos, obtidas através da variação de parâmetros de um filtro de regularização. Para controle da qualidade da restauração utilizamos uma imagem de alta resolução espacial obtida na linha H-a e a PSF do Itapetinga para borrá-la. Pequenos desvios, entre a PSF utilizada para o borramento e a PSF utilizada na restauração, produziram alguns desvios notáveis na imagem restaurada porém a adição de ruído nas simulações de restauração foram mais influentes no cálculo da rugosidade da imagem e portanto mais limitante para a restauração. Apresentamos como nosso primeiro resultado uma imagem em 48 GHz com a presença clara do abrilhantamento de limbo que não estava evidente na imagem original e traços de estruturas filamentares, porém ainda sem grande evidência.

  9. Carnivorous diving beetles of the genus Desmopachria (Coleoptera: Dytiscidae) from Brazil: New species, new records, and a checklist

    PubMed Central

    Braga, Rafael Benzi; Ferreira, Nelson

    2014-01-01

    Abstract Eight new species of DesmopachriaBabington, 1841 are described and illustrated from Brazil: D. dicrophallica sp. nov. , D. disticta sp. nov. , D. grammosticta sp. nov. , D . grandinigra sp. nov. , D. itamontensis sp. nov. , D. leptophallica sp. nov. , D. stethothrix sp. nov. , and D. ukuki sp. nov. The species D. amyaeMiller, 2001 , D. cheiMiller, 1999 , D. margarita Young, 1990, and D. volatidiscaMiller, 2001 are recorded for the first time from Brazil. From species of the Desmopachria reported in Brazil, D. aldessaYoung, 1980 has a new record from Pará state and D. fossulataZimmermann, 1928, D. granoidesYoung, 1986 , and D. laevis Sharp, 1882 have new records from Rio de Janeiro State. A checklist of all Desmopachria recorded from Brazil is presented with notes about some of the localities. Resumo Oito espécies novas de DesmopachriaBabington, 1841 são descritas e ilustradas para o Brasil, D. dicrophallica sp. nov. , D. disticta sp. nov. , D. grammosticta sp. nov. , D . grandinigra sp. nov., D. itamontensis sp. nov., D. leptophallica sp. nov., D. stethothrix sp. nov. e D. ukuki sp. nov. As espécies D. amyaeMiller, 2001, D. cheiMiller, 1999 , D. margarita Young, 1990 e D. volatidiscaMiller, 2001 são registradas pela primeira vez para o Brasil. Das espécies de Desmopachria registradas para o Brasil D. aldessaYoung, 1980 tem um novo registro para o estado do Pará e D. fossulataZimmermann, 1928 , D. granoidesYoung, 1986 e D. laevis Sharp, 1882 têm novos registros para o estado do Rio de Janeiro. Uma listagem de todos os Desmopachria registrados para o Brasil é apresentada, com notas acerca de algumas localidades. PMID:25373202

  10. Radar Data Processing Using a Distributed Computational System

    DTIC Science & Technology

    1992-06-01

    objects to processors must reduce Toc (N) (i.e., the time to compute on 85 N nodes) [Ref. 28]. Time spent communicating can represent a degradation of...de Sistemas e Computaq&o, s/ data. [9] Vilhena R. "IntroduqAo aos Algoritmos para Processamento de Marcaq6es e DistAncias", Escola Naval - Notas de...Aula - Automaq&o de Sistemas Navais, s/ data. (101 Averbuch A., Itzikcwitz S., and Kapon T. "Parallel Implementation of Multiple Model Tracking

  11. Assessment of the usability of a digital learning technology prototype for monitoring intracranial pressure.

    PubMed

    Carvalho, Lilian Regina de; Évora, Yolanda Dora Martinez; Zem-Mascarenhas, Silvia Helena

    2016-08-29

    to assess the usability of a digital learning technology prototype as a new method for minimally invasive monitoring of intracranial pressure. descriptive study using a quantitative approach on assessing the usability of a prototype based on Nielsen's ten heuristics. Four experts in the area of Human-Computer interaction participated in the study. the evaluation delivered eight violated heuristics and 31 usability problems in the 32 screens of the prototype. the suggestions of the evaluators were critical for developing an intuitive, user-friendly interface and will be included in the final version of the digital learning technology. avaliar a usabilidade de um protótipo educacional digital sobre um novo método para monitoração da pressão intracraniana de forma minimamente invasivo para enfermeiros e médicos. estudo descritivo com abordagem quantitativa sobre a avaliação de usabilidade de um protótipo com base nas dez Heurísticas de Nielsen. Participaram quatro especialistas da área de Interação Humano Computador. a avaliação resultou em oito heurísticas violadas e 31 problemas de usabilidade nas 32 telas do protótipo. as sugestões dos avaliadores foram cruciais para o desenvolvimento de uma interface amigável e intuitiva e serão consideradas na versão final da tecnologia educacional digital. evaluar la usabilidad de un prototipo educacional digital sobre un nuevo método para monitorización de la presión intracraneal, de manera mínimamente invasiva. estudio descriptivo con abordaje cuantitativo sobre la evaluación de usabilidad de un prototipo con base en las diez reglas Heurísticas de Nielsen. Participaron cuatro especialistas del área de Interacción Humana Computador. la evaluación resultó en ocho reglas heurísticas violadas y 31 problemas de usabilidad en las 32 pantallas del prototipo. las sugestiones de los evaluadores fueron cruciales para el desarrollo de una interfaz amigable e intuitiva y éstas serán consideradas en la versión final de la tecnología educacional digital.

  12. Biofunctionality and immunocompatibility of starch-based biomaterials

    NASA Astrophysics Data System (ADS)

    Marques, Alexandra Margarida Pinto

    A procura de novos biomateriais que desempenhem funcoes especificas sem, no entanto, desencadearem respostas negativas nos hospedeiros constitui um desafio permanente e actual nesta area. Biomateriais degradaveis foram uma das solucoes propostas e actualmente em aplicacao mas, embora possuam vantagens inegaveis, tambem apresentam alguns problemas nomeadamente no que diz respeito aos seus produtos de degradacao e respectivos efeitos negativos consequentes. Outros biomateriais, entre os quais polimeros de origem natural, foram propostos considerando que os seus produtos de degradacao poderao ser incorporados nas vias metabolicas normais evitando efeitos secundarios no hospedeiro. Ate ao momento, e apesar de todos os esforcos e do grande numero de dispositivos biomedicos desenvolvidos, o biomaterial ideal para uma aplicacao especifica ainda nao foi encontrado. Estudos com polimeros biodegradaveis a base de amido demonstraram que estes materiais possuem propriedades promissoras abrindo novas perspectivas para a sua possivel aplicacao numa variedade de aplicacoes biomedicas. Assim, de modo a demonstrar que estes materiais tem de facto potencial para serem utilizados em, por exemplo, substituicao ossea, sistemas de libertacao controlada, cimentos osseos e engenharia de tecidos, seria imperativo avaliar com maior profundidade a resposta biologica desencadeada pelos mesmos. Para tal foi delineado um plano de trabalhos com tres objectivos principais: i) avaliar a citocompatibilidade dos polimeros e compositos a base de amido com monitorizacao da citotoxicidade e analise da adesao e proliferacao celulares nas suas superficies. Foi dada particular atencao a osteoblastos considerando uma possivel aplicacao ortopedica para estes materiais; ii) estabelecer modelos in vitro para analisar e prever, tanto quanto possivel, uma situacao real de resposta inflamatoria; iii) validar os resultados in vitro com um modelo in vivo ja estabelecido em outros trabalhos de analise da resposta inflamatoria a biomateriais. Em resumo, os estudos de citocompatibilidade e imunocompatibilidade demonstraram que os polimeros e compositos a base de milho sao biomateriais promissores. Em comparacao com os biomateriais degradaveis actualmente em uso, possuem propriedades capazes de induzir um comportamento semelhante, ou mesmo melhor, em termos de citotoxicidade. Estes dados foram reconfirmados com a adesao e proliferacao de celulas do tipo osteoblastos na superficie de alguns dos materiais a base de amido, que demonstraram ser comparaveis as observadas no PLLA, evidenciando a possibilidade de usar esses materiais em aplicacoes ortopedicas. As conclusoes retiradas dos estudos in vitro e in vivo de imunocompatibilidade reforcam as observacoes das experiencias de citocompatibilidade e em conjunto, evidenciam a possibilidade de utilizacao dos biomateriais a base de amido, com fraca capacidade de desencadear uma reaccao inflamatoria, em aplicacoes biomedicas. (Abstract shortened by ProQuest.).

  13. Formación y evolución de planetas gigantes

    NASA Astrophysics Data System (ADS)

    Benvenuto, O. G.; Brunini, A.

    Presentamos el estado actual del trabajo que estamos realizando en el estudio de la formación de planetas gigantes. Detallamos los algoritmos numéricos necesarios para realizar este tipo de cálculo. Presentamos algunos resultados de la formación de objetos con masas de hasta una docena de veces la del planeta Júpiter, resaltando las principales caracteríticas. Finalmente detallamos los problemas que pensamos abordar en un futuro cercano en este tema de investigación.

  14. Código árbol paralelizado para simulaciones astrofísicas. Experimentos de encuentros de galaxias compuestas

    NASA Astrophysics Data System (ADS)

    Viturro, H. R.; Carpintero, D. D.

    Se describe la implementación de un código árbol octal paralelizado desarrollado por los autores. Este código permite la integración del problema de N--cuerpos simultáneamente en varias computadoras (``cluster''), lo que permite desarrollar altas velocidades de cálculo. Se muestran los resultados de algunas integraciones de encuentros entre galaxias de disco con bulbo y halo, generadas mediante algoritmos no utilizados hasta el momento en este campo.

  15. A Molecular Portrait of De Novo Genes in Yeasts.

    PubMed

    Vakirlis, Nikolaos; Hebert, Alex S; Opulente, Dana A; Achaz, Guillaume; Hittinger, Chris Todd; Fischer, Gilles; Coon, Joshua J; Lafontaine, Ingrid

    2018-03-01

    New genes, with novel protein functions, can evolve "from scratch" out of intergenic sequences. These de novo genes can integrate the cell's genetic network and drive important phenotypic innovations. Therefore, identifying de novo genes and understanding how the transition from noncoding to coding occurs are key problems in evolutionary biology. However, identifying de novo genes is a difficult task, hampered by the presence of remote homologs, fast evolving sequences and erroneously annotated protein coding genes. To overcome these limitations, we developed a procedure that handles the usual pitfalls in de novo gene identification and predicted the emergence of 703 de novo gene candidates in 15 yeast species from 2 genera whose phylogeny spans at least 100 million years of evolution. We validated 85 candidates by proteomic data, providing new translation evidence for 25 of them through mass spectrometry experiments. We also unambiguously identified the mutations that enabled the transition from noncoding to coding for 30 Saccharomyces de novo genes. We established that de novo gene origination is a widespread phenomenon in yeasts, only a few being ultimately maintained by selection. We also found that de novo genes preferentially emerge next to divergent promoters in GC-rich intergenic regions where the probability of finding a fortuitous and transcribed ORF is the highest. Finally, we found a more than 3-fold enrichment of de novo genes at recombination hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic recombination contributes to de novo gene emergence in yeasts.

  16. Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

    PubMed

    Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

    2016-01-01

    De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. To describe the overall pattern of de novo cancers in liver transplant recipients. Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

  17. Self-referencing thermometry in the nanoscale =

    NASA Astrophysics Data System (ADS)

    Brites, Carlos Antonio Delgado Sousa

    Na ultima decada emergiu uma linha de investigacao muito activa em termometros nao invasivos e precisos que possam determinar temperatura a escala nanometrica. Esta investigacao foi fortemente estimulada pelas numerosas solicitacoes da nanotecnologia e da biomedicina, por exemplo. Uma das abordagens mais promissoras propoe o uso de ioes trivalentes de lantanideos que apresenta propriedades fotoluminescentes que dependem da temperatura. Neste trabalho demonstra-se que esta tecnica combina as vantagens de te um limite de deteccao de 0.5 graus com sensibilidade ate 4.5 % K-1. Este termometro molecular pode ser processado em filmes finos ou nanoparticulas, abrindo os campos de aplicacao a diferentes utilizacoes. As nanoparticulas de silica produzidas sao caracterizadas na presenca e na ausencia de ioes lantanideos. Sem o metal, as nanoparticulas de APTES/TEOS demonstram ser luminescentes sob excitacao UV sem necessidade de utilizar qualquer tratamento termico. O rendimento quantico de emissao depende apenas da proporcao dos silanos e pode atingir o valor de 0.15 +/- 0.02. A co-dopagem destas nanoparticulas com Eu3+ e Tb3+ permite obter sondas com resposta raciometrica, com a possibilidade de ajustar a gama de temperaturas de operacao e a sensibilidade, via desenho inteligente da matriz de suporte e dos ligandos de beta-dicetona que estao coordenados ao iao metalico. Quando processados como filmes, este termometro permite o mapeamento de temperaturas com resolucao espacial 1.8 mum. A racionalizacao da dependencia de temperatura e uma ferramenta util para desenvolver termometros que operam em gamas de temperatura especificos (e.g. gama de temperatura fisiologica, 290-340 K) com sensibilidade acima de 0.5 % K-1. A combinacao de esforcos de um grande numero de diversas disciplinas ira previsivelmente permitir o surgimento de termometros moleculares novos e sofisticados, preenchendo os principais requisitos das nanociencias.

  18. De novo peptide sequencing by deep learning

    PubMed Central

    Tran, Ngoc Hieu; Zhang, Xianglilan; Xin, Lei; Shan, Baozhen; Li, Ming

    2017-01-01

    De novo peptide sequencing from tandem MS data is the key technology in proteomics for the characterization of proteins, especially for new sequences, such as mAbs. In this study, we propose a deep neural network model, DeepNovo, for de novo peptide sequencing. DeepNovo architecture combines recent advances in convolutional neural networks and recurrent neural networks to learn features of tandem mass spectra, fragment ions, and sequence patterns of peptides. The networks are further integrated with local dynamic programming to solve the complex optimization task of de novo sequencing. We evaluated the method on a wide variety of species and found that DeepNovo considerably outperformed state of the art methods, achieving 7.7–22.9% higher accuracy at the amino acid level and 38.1–64.0% higher accuracy at the peptide level. We further used DeepNovo to automatically reconstruct the complete sequences of antibody light and heavy chains of mouse, achieving 97.5–100% coverage and 97.2–99.5% accuracy, without assisting databases. Moreover, DeepNovo is retrainable to adapt to any sources of data and provides a complete end-to-end training and prediction solution to the de novo sequencing problem. Not only does our study extend the deep learning revolution to a new field, but it also shows an innovative approach in solving optimization problems by using deep learning and dynamic programming. PMID:28720701

  19. De Novo ORFs in Drosophila Are Important to Organismal Fitness and Evolved Rapidly from Previously Non-coding Sequences

    PubMed Central

    Reinhardt, Josephine A.; Wanjiru, Betty M.; Brant, Alicia T.; Saelao, Perot; Begun, David J.; Jones, Corbin D.

    2013-01-01

    How non-coding DNA gives rise to new protein-coding genes (de novo genes) is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution of an open reading frame. In contrast, four other de novo genes evolved a translated open reading frame and transcription within the same evolutionary interval suggesting that nascent open reading frames (proto-ORFs), while not required, can contribute to the emergence of a new de novo gene. However, none of the genes arose from proto-ORFs that existed long before expression evolved. Sequence and structural evolution of de novo genes was rapid compared to nearby genes and the structural complexity of de novo genes steadily increases over evolutionary time. Despite the fact that these genes are transcribed at a higher level in males than females, and are most strongly expressed in testes, RNAi experiments show that most of these genes are essential in both sexes during metamorphosis. This lethality suggests that protein coding de novo genes in Drosophila quickly become functionally important. PMID:24146629

  20. Genes from scratch--the evolutionary fate of de novo genes.

    PubMed

    Schlötterer, Christian

    2015-04-01

    Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  1. De novo malignancy after pancreas transplantation in Japan.

    PubMed

    Tomimaru, Y; Ito, T; Marubashi, S; Kawamoto, K; Tomokuni, A; Asaoka, T; Wada, H; Eguchi, H; Mori, M; Doki, Y; Nagano, H

    2015-04-01

    Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. We clarified the incidence of de novo malignancy after pancreas transplantation in Japan. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A Comprehensive Analysis of Transcript-Supported De Novo Genes in Saccharomyces sensu stricto Yeasts

    PubMed Central

    Lu, Tzu-Chiao; Leu, Jun-Yi; Lin, Wen-Chang

    2017-01-01

    Abstract Novel genes arising from random DNA sequences (de novo genes) have been suggested to be widespread in the genomes of different organisms. However, our knowledge about the origin and evolution of de novo genes is still limited. To systematically understand the general features of de novo genes, we established a robust pipeline to analyze >20,000 transcript-supported coding sequences (CDSs) from the budding yeast Saccharomyces cerevisiae. Our analysis pipeline combined phylogeny, synteny, and sequence alignment information to identify possible orthologs across 20 Saccharomycetaceae yeasts and discovered 4,340 S. cerevisiae-specific de novo genes and 8,871 S. sensu stricto-specific de novo genes. We further combine information on CDS positions and transcript structures to show that >65% of de novo genes arose from transcript isoforms of ancient genes, especially in the upstream and internal regions of ancient genes. Fourteen identified de novo genes with high transcript levels were chosen to verify their protein expressions. Ten of them, including eight transcript isoform-associated CDSs, showed translation signals and five proteins exhibited specific cytosolic localizations. Our results suggest that de novo genes frequently arise in the S. sensu stricto complex and have the potential to be quickly integrated into ancient cellular network. PMID:28981695

  3. Incidence and Management of De Novo Lower Urinary Tract Symptoms After Pelvic Organ Prolapse Repair.

    PubMed

    Tran, Henry; Chung, Doreen E

    2017-09-12

    Pelvic organ prolapse (POP) is a significant problem with many options for surgical correction. Following prolapse surgery, de novo lower urinary tract symptoms (LUTS) are not uncommon. We review the current literature on de novo lower urinary tract symptoms following POP repair and discuss the role of urodynamics in the evaluation of the prolapse patient. Patients with occult stress urinary incontinence (SUI) appear to be at higher risk of developing de novo SUI after POP repair. Prolapse reduction in patients undergoing urodynamic evaluation is important. Different types of POP repair influence rates of de novo SUI. Also, prophylactic anti-incontinence procedures at time of POP repair appear to lower the incidence of de novo SUI, but at the cost of increased risk of complications and morbidity. Pre-existing overactive bladder (OAB) symptoms may either improve or persist, and de novo OAB can develop. The specific role of urodynamic study testing for POP is still being determined. Increasingly, women are seeking surgical treatment for POP. Aside from complications related to surgery in general, proper patient counseling is important regarding the risk of development of de novo voiding problems following surgery. Despite a growing body of literature looking at de novo voiding symptoms after prolapse repair, more studies are still needed.

  4. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy.

    PubMed

    Hui, Chee-Kin; Cheung, Winnie W W; Zhang, Hai-Ying; Au, Wing-Yan; Yueng, Yui-Hung; Leung, Anskar Y H; Leung, Nancy; Luk, John M; Lie, Albert K W; Kwong, Yok-Lam; Liang, Raymond; Lau, George K K

    2006-07-01

    De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy. Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion. Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001). Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.

  5. 12 CFR 1263.14 - De novo insured depository institution applicants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false De novo insured depository institution... MEMBERS OF THE BANKS Eligibility Requirements § 1263.14 De novo insured depository institution applicants... (de novo applicant) is deemed to meet the requirements of §§ 1263.7, 1263.8, 1263.11 and 1263.12. (b...

  6. 12 CFR 925.14 - De novo insured depository institution applicants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false De novo insured depository institution... MEMBERS AND HOUSING ASSOCIATES MEMBERS OF THE BANKS Eligibility Requirements § 925.14 De novo insured... application for membership in the Bank (de novo applicant) is deemed to meet the requirements of §§ 925.7, 925...

  7. 43 CFR 30.207 - What happens if nobody files for de novo review?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What happens if nobody files for de novo... PROBATE HEARINGS PROCEDURES Summary Probate Proceedings § 30.207 What happens if nobody files for de novo review? If no interested party requests de novo review within 30 days of the date of the written decision...

  8. 43 CFR 30.207 - What happens if nobody files for de novo review?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false What happens if nobody files for de novo... PROBATE HEARINGS PROCEDURES Summary Probate Proceedings § 30.207 What happens if nobody files for de novo review? If no interested party requests de novo review within 30 days of the date of the written decision...

  9. GlycoDeNovo - an Efficient Algorithm for Accurate de novo Glycan Topology Reconstruction from Tandem Mass Spectra

    NASA Astrophysics Data System (ADS)

    Hong, Pengyu; Sun, Hui; Sha, Long; Pu, Yi; Khatri, Kshitij; Yu, Xiang; Tang, Yang; Lin, Cheng

    2017-08-01

    A major challenge in glycomics is the characterization of complex glycan structures that are essential for understanding their diverse roles in many biological processes. We present a novel efficient computational approach, named GlycoDeNovo, for accurate elucidation of the glycan topologies from their tandem mass spectra. Given a spectrum, GlycoDeNovo first builds an interpretation-graph specifying how to interpret each peak using preceding interpreted peaks. It then reconstructs the topologies of peaks that contribute to interpreting the precursor ion. We theoretically prove that GlycoDeNovo is highly efficient. A major innovative feature added to GlycoDeNovo is a data-driven IonClassifier which can be used to effectively rank candidate topologies. IonClassifier is automatically learned from experimental spectra of known glycans to distinguish B- and C-type ions from all other ion types. Our results showed that GlycoDeNovo is robust and accurate for topology reconstruction of glycans from their tandem mass spectra. [Figure not available: see fulltext.

  10. A gradient-boosting approach for filtering de novo mutations in parent-offspring trios.

    PubMed

    Liu, Yongzhuang; Li, Bingshan; Tan, Renjie; Zhu, Xiaolin; Wang, Yadong

    2014-07-01

    Whole-genome and -exome sequencing on parent-offspring trios is a powerful approach to identifying disease-associated genes by detecting de novo mutations in patients. Accurate detection of de novo mutations from sequencing data is a critical step in trio-based genetic studies. Existing bioinformatic approaches usually yield high error rates due to sequencing artifacts and alignment issues, which may either miss true de novo mutations or call too many false ones, making downstream validation and analysis difficult. In particular, current approaches have much worse specificity than sensitivity, and developing effective filters to discriminate genuine from spurious de novo mutations remains an unsolved challenge. In this article, we curated 59 sequence features in whole genome and exome alignment context which are considered to be relevant to discriminating true de novo mutations from artifacts, and then employed a machine-learning approach to classify candidates as true or false de novo mutations. Specifically, we built a classifier, named De Novo Mutation Filter (DNMFilter), using gradient boosting as the classification algorithm. We built the training set using experimentally validated true and false de novo mutations as well as collected false de novo mutations from an in-house large-scale exome-sequencing project. We evaluated DNMFilter's theoretical performance and investigated relative importance of different sequence features on the classification accuracy. Finally, we applied DNMFilter on our in-house whole exome trios and one CEU trio from the 1000 Genomes Project and found that DNMFilter could be coupled with commonly used de novo mutation detection approaches as an effective filtering approach to significantly reduce false discovery rate without sacrificing sensitivity. The software DNMFilter implemented using a combination of Java and R is freely available from the website at http://humangenome.duke.edu/software. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy.

    PubMed

    Rossi, Valentina; Nolè, Franco; Redana, Stefania; Adamoli, Laura; Martinello, Rossella; Aurilio, Gaetano; Verri, Elena; Sapino, Anna; Viale, Giuseppe; Aglietta, Massimo; Montemurro, Filippo

    2014-02-01

    Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings. Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Silva E Costa, S.

    2003-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Costa, Jose Diogo Teixeira Barbosa

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

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

    NASA Astrophysics Data System (ADS)

    Silva, Nuno Joao de Oliveira

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

  15. 43 CFR 30.206 - What happens after I file a request for de novo review?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false What happens after I file a request for de... request for de novo review? (a) Within 10 days of receiving a request for de novo review, OHA will notify... the de novo review, and assign the case to a judge. (b) The judge will review the merits of the case...

  16. 43 CFR 30.206 - What happens after I file a request for de novo review?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What happens after I file a request for de... request for de novo review? (a) Within 10 days of receiving a request for de novo review, OHA will notify... the de novo review, and assign the case to a judge. (b) The judge will review the merits of the case...

  17. De novo mutations in regulatory elements in neurodevelopmental disorders

    PubMed Central

    Short, Patrick J.; McRae, Jeremy F.; Gallone, Giuseppe; Sifrim, Alejandro; Won, Hyejung; Geschwind, Daniel H.; Wright, Caroline F.; Firth, Helen V; FitzPatrick, David R.; Barrett, Jeffrey C.; Hurles, Matthew E.

    2018-01-01

    We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders. PMID:29562236

  18. De Novo duplication in Charcot-Marie-Tooth Type 1A

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

    Mandich, P.; Bellone, E.; Ajmar, F.

    1996-09-01

    We read with interest the paper on {open_quotes}Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1A: First Report of a De Novo Duplication with a Maternal Origin,{close_quotes}. They reported their experience with 10 sporadic cases of Charcot-Marie-Tooth type 1A (CMT1A) in which it was demonstrated that the disease had arisen as the result of a de novo duplication. They analyzed the de novo-duplication families by using microsatellite markers and identified the parental origin of the duplication in eight cases. In one family the duplication was of maternal origin, whereas in the remaining seven cases it was ofmore » paternal origin. The authors concluded that their report was the first evidence of a de novo duplication of maternal origin, suggesting that this is not a phenomenon associated solely with male meiosis. 7 refs.« less

  19. Combined "de novo" and "ex novo" lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis.

    PubMed

    Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Qi, Gao-Xiang; Xiong, Lian; Lin, Xiao-Qing; Wang, Can; Li, Hai-Long; Chen, Xin-De

    2017-01-01

    Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways (" de novo " lipid fermentation and " ex novo " lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both " de novo " and " ex novo " lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined " de novo " and " ex novo " lipid fermentation by oleaginous yeast Trichosporon dermatis . Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis . Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis . The present study proves the potential and possibility of combined " de novo " and " ex novo " lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

  20. Geosmithia-Ophiostoma: a New Fungus-Fungus Association.

    PubMed

    Pepori, Alessia L; Bettini, Priscilla P; Comparini, Cecilia; Sarrocco, Sabrina; Bonini, Anna; Frascella, Arcangela; Ghelardini, Luisa; Scala, Aniello; Vannacci, Giovanni; Santini, Alberto

    2018-04-01

    In Europe as in North America, elms are devastated by Dutch elm disease (DED), caused by the alien ascomycete Ophiostoma novo-ulmi. Pathogen dispersal and transmission are ensured by local species of bark beetles, which established a novel association with the fungus. Elm bark beetles also transport the Geosmithia fungi genus that is found in scolytids' galleries colonized by O. novo-ulmi. Widespread horizontal gene transfer between O. novo-ulmi and Geosmithia was recently observed. In order to define the relation between these two fungi in the DED pathosystem, O. novo-ulmi and Geosmithia species from elm, including a GFP-tagged strain, were grown in dual culture and mycelial interactions were observed by light and fluorescence microscopy. Growth and sporulation of O. novo-ulmi in the absence or presence of Geosmithia were compared. The impact of Geosmithia on DED severity was tested in vivo by co-inoculating Geosmithia and O. novo-ulmi in elms. A close and stable relation was observed between the two fungi, which may be classified as mycoparasitism by Geosmithia on O. novo-ulmi. These results prove the existence of a new component in the complex of organisms involved in DED, which might be capable of reducing the disease impact.

  1. Spectra library assisted de novo peptide sequencing for HCD and ETD spectra pairs.

    PubMed

    Yan, Yan; Zhang, Kaizhong

    2016-12-23

    De novo peptide sequencing via tandem mass spectrometry (MS/MS) has been developed rapidly in recent years. With the use of spectra pairs from the same peptide under different fragmentation modes, performance of de novo sequencing is greatly improved. Currently, with large amount of spectra sequenced everyday, spectra libraries containing tens of thousands of annotated experimental MS/MS spectra become available. These libraries provide information of the spectra properties, thus have the potential to be used with de novo sequencing to improve its performance. In this study, an improved de novo sequencing method assisted with spectra library is proposed. It uses spectra libraries as training datasets and introduces significant scores of the features used in our previous de novo sequencing method for HCD and ETD spectra pairs. Two pairs of HCD and ETD spectral datasets were used to test the performance of the proposed method and our previous method. The results show that this proposed method achieves better sequencing accuracy with higher ranked correct sequences and less computational time. This paper proposed an advanced de novo sequencing method for HCD and ETD spectra pair and used information from spectra libraries and significant improved previous similar methods.

  2. A bolus/basal multiple injection regimen in type I diabetes. A multicentre trial using a new 'fountain-pen' device for short-acting human insulin as well as long-acting human insulin.

    PubMed

    Distiller, L A; Robertson, L I; Moore, R; Bonnici, F

    1987-06-20

    A trial was undertaken to ascertain the effect and acceptability of a multiple insulin injection regimen (MII) in patients with insulin-dependent diabetes mellitus using short-acting monocomponent human soluble insulin (Actrapid HM; Novo) for pre-meal bolus injections with the NovoPen injection device (Novo) and long-acting human insulin (Ultratard HM; Novo) at bedtime. Fifty-four patients, all previously on twice-daily short/intermediate-acting human insulin (Monotard HM; Novo) and Actrapid HM, were randomly selected. There was a significant overall improvement in diabetic control over the 12 weeks of the trial, the glycosylated haemoglobin (Hb A1) dropping from a mean of 9.8 +/- 2.2% to 8.6 +/- 1.7% (P less than 0.05). MII, using the NovoPen, was found to be more convenient than conventional insulin administration by 92% of the subjects. It is concluded that the NovoPen is a useful and convenient means of administering pre-meal boluses in an MII regimen, with a very high rate of acceptance by patients of all ages.

  3. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    PubMed Central

    Willsey, A. Jeremy; Fernandez, Thomas V.; Yu, Dongmei; King, Robert A.; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J.; Mandell, Jeffrey D.; Huang, Alden Y.; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E.; Neale, Benjamin M.; Coppola, Giovanni; Mathews, Carol A.; Tischfield, Jay A.; Scharf, Jeremiah M.; State, Matthew W.; Heiman, Gary A.

    2017-01-01

    SUMMARY Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. PMID:28472652

  4. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    PubMed

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

    2018-01-01

    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  5. De novo activation of HBV with escape mutations from hepatitis B surface antibody after living donor liver transplantation.

    PubMed

    Ueda, Yoshihide; Marusawa, Hiroyuki; Egawa, Hiroto; Okamoto, Shinya; Ogura, Yasuhiro; Oike, Fumitaka; Nishijima, Norihiro; Takada, Yasutsugu; Uemoto, Shinji; Chiba, Tsutomu

    2011-01-01

    De novo activation of HBV occurs after liver transplantation from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive donors, even under hepatitis B immunoglobulin (HBIG) prophylaxis. One reason for the activation of HBV is the emergence of HBV with escape mutations from hepatitis B surface antibody (anti-HBs). The aim of this study is to clarify the clinical features for de novo activation of HBV with anti-HBs escape mutations after liver transplantation. Clinical features of 75 patients who received HBIG prophylaxis >6 months after liver transplantation with liver grafts from anti-HBc-positive donors were retrospectively analysed. Among the 75 recipients, 19 (25%) developed de novo activation of HBV. Of the 19 recipients, the emergence of HBV with anti-HBs escape mutations was confirmed in 7 patients. The rate of de novo activation of HBV with anti-HBs escape mutations was 12% at 5 years. Sequence analysis revealed mutations in the common 'a' determinant region of the surface gene, including G145R, G145A and Q129P, in HBsAg. Administration of entecavir immediately after the occurrence of de novo HBV activation resolved hepatitis and induced clearance of serum HBsAg and HBV DNA in all four patients receiving entecavir. Escape mutations from anti-HBs caused de novo activation of HBV under HBIG prophylaxis after liver transplantation. Early administration of entecavir was effective on de novo activation of HBV with anti-HBs escape mutations.

  6. 47 CFR 54.723 - Standard of review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Competition Bureau shall conduct de novo review of request for review of decisions issue by the Administrator. (b) The Federal Communications Commission shall conduct de novo review of requests for review of... the Commission shall not conduct de novo review of decisions issued by the Wireline Competition Bureau...

  7. 47 CFR 54.723 - Standard of review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Competition Bureau shall conduct de novo review of request for review of decisions issue by the Administrator. (b) The Federal Communications Commission shall conduct de novo review of requests for review of... the Commission shall not conduct de novo review of decisions issued by the Wireline Competition Bureau...

  8. A review of 25 years' experience with the NovoPen family of insulin pens in the management of diabetes mellitus.

    PubMed

    Hyllested-Winge, Jacob; Jensen, Klaus H; Rex, Jørn

    2010-01-01

    NovoPen, the first insulin pen, was introduced in 1985. This review article is an update of a review paper published in 2006 on 20 years' use of the NovoPen family of insulin pens in the management of diabetes mellitus. The literature searches conducted in the earlier review article were updated with search results for new articles published since April 2005. This was followed by an iterative search of references cited in identified publications and by searches of abstracts from proceedings of major international diabetes conferences since 2005. Most of the original studies identified in the 2006 review showed that insulin regimens using the NovoPen family of insulin pens were at least as effective (and in some cases superior) in maintaining glycaemic control and were as safe (in terms of hypoglycaemia) as conventional insulin regimens employing vials and syringes. Most patients preferred the various NovoPen insulin pens over vials and syringes, with some evidence suggesting that the use of discreet devices, such as those of the NovoPen family, facilitates intensive insulin therapy regimens, thereby helping to improve lifestyle flexibility. The new search results showed that the current generation of the device for the adult population, NovoPen 4, retains these benefits and further meets patients' needs by improving ease of use, convenience and discretion, which may be particularly important for those with manual dexterity, visual or auditory impairments. There was also evidence that healthcare professionals would be more likely to recommend NovoPen 4 to their patients than other devices. The recently introduced NovoPen Echo, designed specifically for the paediatric population, combines half-increment dosing with a memory function that can be used to retrieve information about the time and amount of the last dose, potentially reducing the fear of double dosing or missing a dose. Evidence obtained from the new searches suggested that paediatric patients, their parents and healthcare professionals were highly satisfied with NovoPen Echo overall, with most paediatric patients rating it their favourite pen compared with other insulin pens. In conclusion, new data published over the last 5 years on the use of NovoPen devices add to the large body of published evidence supporting the patient-related benefits of durable insulin injection pens in the treatment of diabetes since the first such pen was introduced in 1985. Together, the benefits of NovoPen are considered likely to improve both patients' quality of life and their compliance with therapy.

  9. De Novo Origin of Human Protein-Coding Genes

    PubMed Central

    Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

    2011-01-01

    The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

  10. De novo mutations in histone modifying genes in congenital heart disease

    PubMed Central

    Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D.; Romano-Adesman, Angela; Bjornson, Robert D.; Breitbart, Roger E.; Brown, Kerry K.; Carriero, Nicholas J.; Cheung, Yee Him; Deanfield, John; DePalma, Steve; Fakhro, Khalid A.; Glessner, Joseph; Hakonarson, Hakon; Italia, Michael; Kaltman, Jonathan R.; Kaski, Juan; Kim, Richard; Kline, Jennie K.; Lee, Teresa; Leipzig, Jeremy; Lopez, Alexander; Mane, Shrikant M.; Mitchell, Laura E.; Newburger, Jane W.; Parfenov, Michael; Pe'er, Itsik; Porter, George; Roberts, Amy; Sachidanandam, Ravi; Sanders, Stephan J.; Seiden, Howard S.; State, Mathew W.; Subramanian, Sailakshmi; Tikhonova, Irina R.; Wang, Wei; Warburton, Dorothy; White, Peter S.; Williams, Ismee A.; Zhao, Hongyu; Seidman, Jonathan G.; Brueckner, Martina; Chung, Wendy K.; Gelb, Bruce D.; Goldmuntz, Elizabeth; Seidman, Christine E.; Lifton, Richard P.

    2013-01-01

    Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD. PMID:23665959

  11. Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

    PubMed

    Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

    2017-03-22

    The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  12. Atomic layer deposition of metal oxide by non-aqueous sol-gel chemistry =

    NASA Astrophysics Data System (ADS)

    Marichy, Catherine

    O trabalho apresentado neste manuscrito foi desenvolvido no ambito do programa doutoral intitulado “Deposicao de Camadas Atomicas (ALD) de oxido de metais por sol-gel nao-aquoso”. O objectivo deste trabalho foi a preparacao de hetero-estruturas funcionais por ALD e a sua caracterizacao. Foi desenvolvido um novo processo de deposicao de oxido de estanho a temperatura baixa-moderada, utilizando um metodo ALD nao-aquoso, o qual foi aplicado com sucesso ao revestimento controlado das paredes internas e externas de nanotubos de carbono. Uma vez que a preparacao de nanomateriais funcionais requer uma elevada exatidao do processo de deposicao, foi demonstrada a deposicao precisa de filmes que se adaptem a forma do substrato ou de filmes nano-estruturados constituidos por particulas em varios substratos. Alem disso, foram depositados com grande exatidao varios oxidos de metal em nanotubos de carbono e demonstrou-se a possibilidade de ajustar o revestimento feito por ALD atraves do controlo da funcionalizacao da superficie do substrato nano-estruturado de carbono. As hetero-estruturas obtidas foram posteriormente aplicadas como sensores de gases. O melhoramento verificado na sensibilidade foi atribuido a formacao de heterojuncoes p-n entre o filme de oxido de metais e o suporte. O trabalho desenvolvido tendo como objetivo o controlo do revestimento por ALD atraves da funcionalizacao da superficie do suporte e certamente de interesse para o design de hetero-estruturas funcionais baseadas em substratos de carbono. De facto, durante o ultimo periodo do programa de doutoramento, este conceito foi alargado a funcionalizacao e revestimento com oxidos de metal de fibras de carbono preparadas por “electrospinning”, de forma a melhorar a estabilidade e a atividade eletrocatalitica de catalisadores a base de Pt. Este trabalho foi realizado maioritariamente na Universidade de Aveiro mas tambem na Universidade Nacional de Seul e beneficiou de varias colaboracoes internacionais devido a natureza multidisciplinar da area de investigacao em que esta inserido.

  13. Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies.

    PubMed

    Kubal, Chandrashekhar; Mangus, Richard; Saxena, Romil; Lobashevsky, Andrew; Higgins, Nancy; Fridell, Jonathan; Tector, A Joseph

    2015-08-01

    Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liver-excluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibody-mediated rejection was diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusing mechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.

  14. Mass spectrometry-based protein identification by integrating de novo sequencing with database searching.

    PubMed

    Wang, Penghao; Wilson, Susan R

    2013-01-01

    Mass spectrometry-based protein identification is a very challenging task. The main identification approaches include de novo sequencing and database searching. Both approaches have shortcomings, so an integrative approach has been developed. The integrative approach firstly infers partial peptide sequences, known as tags, directly from tandem spectra through de novo sequencing, and then puts these sequences into a database search to see if a close peptide match can be found. However the current implementation of this integrative approach has several limitations. Firstly, simplistic de novo sequencing is applied and only very short sequence tags are used. Secondly, most integrative methods apply an algorithm similar to BLAST to search for exact sequence matches and do not accommodate sequence errors well. Thirdly, by applying these methods the integrated de novo sequencing makes a limited contribution to the scoring model which is still largely based on database searching. We have developed a new integrative protein identification method which can integrate de novo sequencing more efficiently into database searching. Evaluated on large real datasets, our method outperforms popular identification methods.

  15. Stem-Loop RNA Hairpins in Giant Viruses: Invading rRNA-Like Repeats and a Template Free RNA

    PubMed Central

    Seligmann, Hervé; Raoult, Didier

    2018-01-01

    We examine the hypothesis that de novo template-free RNAs still form spontaneously, as they did at the origins of life, invade modern genomes, contribute new genetic material. Previously, analyses of RNA secondary structures suggested that some RNAs resembling ancestral (t)RNAs formed recently de novo, other parasitic sequences cluster with rRNAs. Here positive control analyses of additional RNA secondary structures confirm ancestral and de novo statuses of RNA grouped according to secondary structure. Viroids with branched stems resemble de novo RNAs, rod-shaped viroids resemble rRNA secondary structures, independently of GC contents. 5′ UTR leading regions of West Nile and Dengue flavivirid viruses resemble de novo and rRNA structures, respectively. An RNA homologous with Megavirus, Dengue and West Nile genomes, copperhead snake microsatellites and levant cotton repeats, not templated by Mimivirus' genome, persists throughout Mimivirus' infection. Its secondary structure clusters with candidate de novo RNAs. The saltatory phyletic distribution and secondary structure of Mimivirus' peculiar RNA suggest occasional template-free polymerization of this sequence, rather than noncanonical transcriptions (swinger polymerization, posttranscriptional editing). PMID:29449833

  16. De Novo Coding Variants Are Strongly Associated with Tourette Disorder.

    PubMed

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei; King, Robert A; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J; Mandell, Jeffrey D; Huang, Alden Y; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E; Neale, Benjamin M; Coppola, Giovanni; Mathews, Carol A; Tischfield, Jay A; Scharf, Jeremiah M; State, Matthew W; Heiman, Gary A

    2017-05-03

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Automated Antibody De Novo Sequencing and Its Utility in Biopharmaceutical Discovery

    NASA Astrophysics Data System (ADS)

    Sen, K. Ilker; Tang, Wilfred H.; Nayak, Shruti; Kil, Yong J.; Bern, Marshall; Ozoglu, Berk; Ueberheide, Beatrix; Davis, Darryl; Becker, Christopher

    2017-05-01

    Applications of antibody de novo sequencing in the biopharmaceutical industry range from the discovery of new antibody drug candidates to identifying reagents for research and determining the primary structure of innovator products for biosimilar development. When murine, phage display, or patient-derived monoclonal antibodies against a target of interest are available, but the cDNA or the original cell line is not, de novo protein sequencing is required to humanize and recombinantly express these antibodies, followed by in vitro and in vivo testing for functional validation. Availability of fully automated software tools for monoclonal antibody de novo sequencing enables efficient and routine analysis. Here, we present a novel method to automatically de novo sequence antibodies using mass spectrometry and the Supernovo software. The robustness of the algorithm is demonstrated through a series of stress tests.

  18. Reference-guided de novo assembly approach improves genome reconstruction for related species.

    PubMed

    Lischer, Heidi E L; Shimizu, Kentaro K

    2017-11-10

    The development of next-generation sequencing has made it possible to sequence whole genomes at a relatively low cost. However, de novo genome assemblies remain challenging due to short read length, missing data, repetitive regions, polymorphisms and sequencing errors. As more and more genomes are sequenced, reference-guided assembly approaches can be used to assist the assembly process. However, previous methods mostly focused on the assembly of other genotypes within the same species. We adapted and extended a reference-guided de novo assembly approach, which enables the usage of a related reference sequence to guide the genome assembly. In order to compare and evaluate de novo and our reference-guided de novo assembly approaches, we used a simulated data set of a repetitive and heterozygotic plant genome. The extended reference-guided de novo assembly approach almost always outperforms the corresponding de novo assembly program even when a reference of a different species is used. Similar improvements can be observed in high and low coverage situations. In addition, we show that a single evaluation metric, like the widely used N50 length, is not enough to properly rate assemblies as it not always points to the best assembly evaluated with other criteria. Therefore, we used the summed z-scores of 36 different statistics to evaluate the assemblies. The combination of reference mapping and de novo assembly provides a powerful tool to improve genome reconstruction by integrating information of a related genome. Our extension of the reference-guided de novo assembly approach enables the application of this strategy not only within but also between related species. Finally, the evaluation of genome assemblies is often not straight forward, as the truth is not known. Thus one should always use a combination of evaluation metrics, which not only try to assess the continuity but also the accuracy of an assembly.

  19. [Administration of activated recombinant factor VII (novo seven) for the control of massive bleeding in gynecology].

    PubMed

    Tanchev, S; Pandurski, F; Georgiev, A; Gesheva, Iu; Platikanov, V; Dinov, P

    2004-01-01

    We report our clinical opinion for recombinant activated factor VII (NovoSeven, Novo Nordisk, Copenhagen, Denmark) administration in gynecology patients with massive haemorrhage. 3 women with gynecology deseases and severe bleeding in recieved NovoSeven in bolus IV. The blood loss and laboratory changes in hematology and haemostasis parameters are monitored. The bleeding was ceased in all cases. Decrease in values of Hb, Er and PTT was noted. The use of recombinant factor VIIA in gynecology patients with severe bleeding is effective and safe enough and could be an alternative to the extreme surgical procedures.

  20. A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis.

    PubMed

    Misselbeck, Karla; Marchetti, Luca; Field, Martha S; Scotti, Marco; Priami, Corrado; Stover, Patrick J

    2017-04-11

    Folate-mediated one-carbon metabolism (FOCM) is an interconnected network of metabolic pathways, including those required for the de novo synthesis of dTMP and purine nucleotides and for remethylation of homocysteine to methionine. Mouse models of folate-responsive neural tube defects (NTDs) indicate that impaired de novo thymidylate (dTMP) synthesis through changes in SHMT expression is causative in folate-responsive NTDs. We have created a hybrid computational model comprised of ordinary differential equations and stochastic simulation. We investigated whether the de novo dTMP synthesis pathway was sensitive to perturbations in FOCM that are known to be associated with human NTDs. This computational model shows that de novo dTMP synthesis is highly sensitive to the common MTHFR C677T polymorphism and that the effect of the polymorphism on FOCM is greater in folate deficiency. Computational simulations indicate that the MTHFR C677T polymorphism and folate deficiency interact to increase the stochastic behavior of the FOCM network, with the greatest instability observed for reactions catalyzed by serine hydroxymethyltransferase (SHMT). Furthermore, we show that de novo dTMP synthesis does not occur in the cytosol at rates sufficient for DNA replication, supporting empirical data indicating that impaired nuclear de novo dTMP synthesis results in uracil misincorporation into DNA.

  1. De novo giant A2 aneurysm following anterior communicating artery occlusion.

    PubMed

    Ibrahim, Tarik F; Hafez, Ahmad; Andrade-Barazarte, Hugo; Raj, Rahul; Niemela, Mika; Lehto, Hanna; Numminen, Jussi; Jarvelainen, Juha; Hernesniemi, Juha

    2015-01-01

    De novo intracranial aneurysms are reported to occur with varying incidence after intracranial aneurysm treatment. They are purported to be observed, however, with increased incidence after Hunterian ligation; particularly in cases of carotid artery occlusion for giant or complex aneurysms deemed unclippable. We report a case of right-sided de novo giant A2 aneurysm 6 years after an anterior communicating artery (ACoA) aneurysm clipping. We believe this de novo aneurysm developed in part due to patient-specific risk factors but also a significant change in cerebral hemodynamics. The ACoA became occluded after surgery that likely altered the cerebral hemodynamics and contributed to the de novo aneurysm. We believe this to be the first reported case of a giant de novo aneurysm in this location. Following parent vessel occlusion (mostly of the carotid artery), there are no reports of any de novo aneurysms in the pericallosal arteries let alone a giant one. The patient had a dominant right A1 and the sudden increase in A2 blood flow likely resulted in increased wall shear stress, particularly in the medial wall of the A2 where the aneurysm occurred 2 mm distal to the A1-2 junction. ACoA preservation is a key element of aneurysm surgery in this location. Suspected occlusion of this vessel may warrant closer radiographic follow-up in patients with other risk factors for aneurysm development.

  2. Dynamic chromatin changes associated with de novo centromere formation in maize euchromatin.

    PubMed

    Su, Handong; Liu, Yalin; Liu, Yong-Xin; Lv, Zhenling; Li, Hongyao; Xie, Shaojun; Gao, Zhi; Pang, Junling; Wang, Xiu-Jie; Lai, Jinsheng; Birchler, James A; Han, Fangpu

    2016-12-01

    The inheritance and function of centromeres are not strictly dependent on any specific DNA sequence, but involve an epigenetic component in most species. CENH3, a centromere histone H3 variant, is one of the best-described epigenetic factors in centromere identity, but the chromatin features required during centromere formation have not yet been revealed. We previously identified two de novo centromeres on Zea mays (maize) minichromosomes derived from euchromatic sites with high-density gene distributions but low-density transposon distributions. The distribution of gene location and gene expression in these sites indicates that transcriptionally active regions can initiate de novo centromere formation, and CENH3 seeding shows a preference for gene-free regions or regions with no gene expression. The locations of the expressed genes detected were at relatively hypomethylated loci, and the altered gene expression resulted from de novo centromere formation, but not from the additional copy of the minichromosome. The initial overall DNA methylation level of the two de novo regions was at a low level, but increased substantially to that of native centromeres after centromere formation. These results illustrate the dynamic chromatin changes during euchromatin-originated de novo centromere formation, which provides insight into the mechanism of de novo centromere formation and regulation of subsequent consequences. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  3. A fragmentation and reassembly method for ab initio phasing.

    PubMed

    Shrestha, Rojan; Zhang, Kam Y J

    2015-02-01

    Ab initio phasing with de novo models has become a viable approach for structural solution from protein crystallographic diffraction data. This approach takes advantage of the known protein sequence information, predicts de novo models and uses them for structure determination by molecular replacement. However, even the current state-of-the-art de novo modelling method has a limit as to the accuracy of the model predicted, which is sometimes insufficient to be used as a template for successful molecular replacement. A fragment-assembly phasing method has been developed that starts from an ensemble of low-accuracy de novo models, disassembles them into fragments, places them independently in the crystallographic unit cell by molecular replacement and then reassembles them into a whole structure that can provide sufficient phase information to enable complete structure determination by automated model building. Tests on ten protein targets showed that the method could solve structures for eight of these targets, although the predicted de novo models cannot be used as templates for successful molecular replacement since the best model for each target is on average more than 4.0 Å away from the native structure. The method has extended the applicability of the ab initio phasing by de novo models approach. The method can be used to solve structures when the best de novo models are still of low accuracy.

  4. 78 FR 38027 - Novo BioPower LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER13-1665-000] Novo BioPower LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding, of Novo BioPower...

  5. UVnovo: A De Novo Sequencing Algorithm Using Single Series of Fragment Ions via Chromophore Tagging and 351 nm Ultraviolet Photodissociation Mass Spectrometry

    PubMed Central

    Robotham, Scott A.; Horton, Andrew P.; Cannon, Joe R.; Cotham, Victoria C.; Marcotte, Edward M.; Brodbelt, Jennifer S.

    2016-01-01

    De novo peptide sequencing by mass spectrometry represents an important strategy for characterizing novel peptides and proteins, in which a peptide’s amino acid sequence is inferred directly from the precursor peptide mass and tandem mass spectrum (MS/MS or MS3) fragment ions, without comparison to a reference proteome. This method is ideal for organisms or samples lacking a complete or well-annotated reference sequence set. One of the major barriers to de novo spectral interpretation arises from confusion of N- and C-terminal ion series due to the symmetry between b and y ion pairs created by collisional activation methods (or c, z ions for electron-based activation methods). This is known as the ‘antisymmetric path problem’ and leads to inverted amino acid subsequences within a de novo reconstruction. Here, we combine several key strategies for de novo peptide sequencing into a single high-throughput pipeline: high efficiency carbamylation blocks lysine side chains, and subsequent tryptic digestion and N-terminal peptide derivatization with the ultraviolet chromophore AMCA yields peptides susceptible to 351 nm ultraviolet photodissociation (UVPD). UVPD-MS/MS of the AMCA-modified peptides then predominantly produces y ions in the MS/MS spectra, specifically addressing the antisymmetric path problem. Finally, the program UVnovo applies a random forest algorithm to automatically learn from and then interpret UVPD mass spectra, passing results to a hidden Markov model for de novo sequence prediction and scoring. We show this combined strategy provides high performance de novo peptide sequencing, enabling the de novo sequencing of thousands of peptides from an E. coli lysate at high confidence. PMID:26938041

  6. Prenatal diagnosis of de novo t(2;18;14)(q33.1;q12.2;q31.2), dup(5)(q34q34), del(7)(p21.1p21.1), and del(10)(q25.3q25.3) and a review of the prenatally ascertained de novo apparently balanced complex and multiple chromosomal rearrangements.

    PubMed

    Chen, Chih-Ping; Chern, Schu-Rern; Lee, Chen-Chi; Lin, Chyi-Chyang; Li, Yueh-Chun; Hsieh, Lie-Jiau; Chen, Wen-Lin; Wang, Wayseen

    2006-02-01

    To present the prenatal diagnosis of a de novo complex chromosomal rearrangement (CCR) associated with de novo interstitial deletions and duplication and to review the literature. Amniocentesis was performed at 18 weeks' gestation because of an increased risk for Down syndrome based on maternal serum alpha-fetoprotein and human chorionic gonadotrophin screening. Amniocentesis revealed a karyotype of 46,XY,t(2;18;14)(q33.1;q12.2;q31.2),dup(5)(q34q34),del(7)(p21.1p21.1), del(10)(q25.3q25.3). The parental karyotypes were normal. The pregnancy was terminated. The fetus manifested facial dysmorphism, clinodactyly of both hands, and hypoplasia of the left great toe. Spectral karyotyping (SKY), cytogenetic polymorphism, and polymorphic DNA markers were used to investigate the imbalances and the origin of the de novo aberrant chromosomes. SKY showed a three-way CCR. Cytogenetic polymorphism investigation of the derivative chromosome 14 of the fetus and the parental chromosomes 14 determined the maternal origin of the translocation. Polymorphic DNA marker analysis confirmed the maternal origin of the de novo interstitial deletions and duplication. No cryptic imbalance at or near the breakpoints of the CCR was detected by the molecular analysis. De novo apparently balanced CCRs may be associated with imbalances in other chromosomes. We suggest further investigation and re-evaluation of cryptic or subtle imbalances in all cases classified as de novo apparently balanced CCRs. Copyright 2006 John Wiley & Sons, Ltd.

  7. in silico Whole Genome Sequencer & Analyzer (iWGS): A Computational Pipeline to Guide the Design and Analysis of de novo Genome Sequencing Studies

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

    Zhou, Xiaofan; Peris, David; Kominek, Jacek

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding its potential for understanding the biology and evolution of the full spectrum of biodiversity. The increasing diversity of sequencing technologies, assays, and de novo assembly algorithms have augmented the complexity of de novo genome sequencing projects in nonmodel organisms. To reduce the costs and challenges in de novo genome sequencing projects and streamline their experimentalmore » design and analysis, we developed iWGS (in silico Whole Genome Sequencer and Analyzer), an automated pipeline for guiding the choice of appropriate sequencing strategy and assembly protocols. iWGS seamlessly integrates the four key steps of a de novo genome sequencing project: data generation (through simulation), data quality control, de novo assembly, and assembly evaluation and validation. The last three steps can also be applied to the analysis of real data. iWGS is designed to enable the user to have great flexibility in testing the range of experimental designs available for genome sequencing projects, and supports all major sequencing technologies and popular assembly tools. Three case studies illustrate how iWGS can guide the design of de novo genome sequencing projects, and evaluate the performance of a wide variety of user-specified sequencing strategies and assembly protocols on genomes of differing architectures. iWGS, along with a detailed documentation, is freely available at https://github.com/zhouxiaofan1983/iWGS.« less

  8. Increased Frequency of De Novo Copy Number Variations in Congenital Heart Disease by Integrative Analysis of SNP Array and Exome Sequence Data

    PubMed Central

    Rodriguez-Murillo, Laura; Fromer, Menachem; Mazaika, Erica; Vardarajan, Badri; Italia, Michael; Leipzig, Jeremy; DePalma, Steven R.; Golhar, Ryan; Sanders, Stephan J.; Yamrom, Boris; Ronemus, Michael; Iossifov, Ivan; Willsey, A. Jeremy; State, Matthew W.; Kaltman, Jonathan R.; White, Peter S.; Shen, Yufeng; Warburton, Dorothy; Brueckner, Martina; Seidman, Christine; Goldmuntz, Elizabeth; Gelb, Bruce D.; Lifton, Richard; Seidman, Jonathan; Hakonarson, Hakon; Chung, Wendy K.

    2014-01-01

    Rationale Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown etiology. Objective To determine the contribution of de novo copy number variants (CNVs) in the etiology of sporadic CHD. Methods and Results We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism (SNP) arrays and/or whole exome sequencing (WES). Results were experimentally validated using digital droplet PCR. We compared validated CNVs in CHD cases to CNVs in 1,301 healthy control trios. The two complementary high-resolution technologies identified 63 validated de novo CNVs in 51 CHD cases. A significant increase in CNV burden was observed when comparing CHD trios with healthy trios, using either SNP array (p=7x10−5, Odds Ratio (OR)=4.6) or WES data (p=6x10−4, OR=3.5) and remained after removing 16% of de novo CNV loci previously reported as pathogenic (p=0.02, OR=2.7). We observed recurrent de novo CNVs on 15q11.2 encompassing CYFIP1, NIPA1, and NIPA2 and single de novo CNVs encompassing DUSP1, JUN, JUP, MED15, MED9, PTPRE SREBF1, TOP2A, and ZEB2, genes that interact with established CHD proteins NKX2-5 and GATA4. Integrating de novo variants in WES and CNV data suggests that ETS1 is the pathogenic gene altered by 11q24.2-q25 deletions in Jacobsen syndrome and that CTBP2 is the pathogenic gene in 10q sub-telomeric deletions. Conclusions We demonstrate a significantly increased frequency of rare de novo CNVs in CHD patients compared with healthy controls and suggest several novel genetic loci for CHD. PMID:25205790

  9. in silico Whole Genome Sequencer & Analyzer (iWGS): A Computational Pipeline to Guide the Design and Analysis of de novo Genome Sequencing Studies

    DOE PAGES

    Zhou, Xiaofan; Peris, David; Kominek, Jacek; ...

    2016-09-16

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding its potential for understanding the biology and evolution of the full spectrum of biodiversity. The increasing diversity of sequencing technologies, assays, and de novo assembly algorithms have augmented the complexity of de novo genome sequencing projects in nonmodel organisms. To reduce the costs and challenges in de novo genome sequencing projects and streamline their experimentalmore » design and analysis, we developed iWGS (in silico Whole Genome Sequencer and Analyzer), an automated pipeline for guiding the choice of appropriate sequencing strategy and assembly protocols. iWGS seamlessly integrates the four key steps of a de novo genome sequencing project: data generation (through simulation), data quality control, de novo assembly, and assembly evaluation and validation. The last three steps can also be applied to the analysis of real data. iWGS is designed to enable the user to have great flexibility in testing the range of experimental designs available for genome sequencing projects, and supports all major sequencing technologies and popular assembly tools. Three case studies illustrate how iWGS can guide the design of de novo genome sequencing projects, and evaluate the performance of a wide variety of user-specified sequencing strategies and assembly protocols on genomes of differing architectures. iWGS, along with a detailed documentation, is freely available at https://github.com/zhouxiaofan1983/iWGS.« less

  10. Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data.

    PubMed

    Glessner, Joseph T; Bick, Alexander G; Ito, Kaoru; Homsy, Jason; Rodriguez-Murillo, Laura; Fromer, Menachem; Mazaika, Erica; Vardarajan, Badri; Italia, Michael; Leipzig, Jeremy; DePalma, Steven R; Golhar, Ryan; Sanders, Stephan J; Yamrom, Boris; Ronemus, Michael; Iossifov, Ivan; Willsey, A Jeremy; State, Matthew W; Kaltman, Jonathan R; White, Peter S; Shen, Yufeng; Warburton, Dorothy; Brueckner, Martina; Seidman, Christine; Goldmuntz, Elizabeth; Gelb, Bruce D; Lifton, Richard; Seidman, Jonathan; Hakonarson, Hakon; Chung, Wendy K

    2014-10-24

    Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism arrays and whole exome sequencing. Results were experimentally validated using digital droplet polymerase chain reaction. We compared validated CNVs in CHD cases with CNVs in 1301 healthy control trios. The 2 complementary high-resolution technologies identified 63 validated de novo CNVs in 51 CHD cases. A significant increase in CNV burden was observed when comparing CHD trios with healthy trios, using either single nucleotide polymorphism array (P=7×10(-5); odds ratio, 4.6) or whole exome sequencing data (P=6×10(-4); odds ratio, 3.5) and remained after removing 16% of de novo CNV loci previously reported as pathogenic (P=0.02; odds ratio, 2.7). We observed recurrent de novo CNVs on 15q11.2 encompassing CYFIP1, NIPA1, and NIPA2 and single de novo CNVs encompassing DUSP1, JUN, JUP, MED15, MED9, PTPRE SREBF1, TOP2A, and ZEB2, genes that interact with established CHD proteins NKX2-5 and GATA4. Integrating de novo variants in whole exome sequencing and CNV data suggests that ETS1 is the pathogenic gene altered by 11q24.2-q25 deletions in Jacobsen syndrome and that CTBP2 is the pathogenic gene in 10q subtelomeric deletions. We demonstrate a significantly increased frequency of rare de novo CNVs in CHD patients compared with healthy controls and suggest several novel genetic loci for CHD. © 2014 American Heart Association, Inc.

  11. Exome sequencing supports a de novo mutational paradigm for schizophrenia

    PubMed Central

    Xu, Bin; Roos, J. Louw; Dexheimer, Phillip; Boone, Braden; Plummer, Brooks; Levy, Shawn; Gogos, Joseph A.; Karayiorgou, Maria

    2011-01-01

    Despite high heritability, a large fraction of cases with schizophrenia do not have a family history of the disease (sporadic cases). Here, we examine the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exome of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 patients affecting 40 genes including a potentially disruptive mutation in DGCR2, a gene removed by the recurrent schizophrenia-predisposing 22q11.2 microdeletion. Comparison to rare inherited variants revealed that the identified de novo mutations show a large excess of nonsynonymous changes in cases, as well as a greater potential to affect protein structure and function. Our analysis reveals a major role of de novo mutations in schizophrenia and also a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. PMID:21822266

  12. De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia

    PubMed Central

    Xu, Bin; Ionita-Laza, Iuliana; Roos, J. Louw; Boone, Braden; Woodrick, Scarlet; Sun, Yan; Levy, Shawn; Gogos, Joseph A.; Karayiorgou, Maria

    2013-01-01

    To evaluate evidence for de novo etiologies in schizophrenia, we sequenced at high coverage the exomes of families recruited from two populations with distinct demographic structure and history. We sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases, as well as 34 unaffected trios. We observed in cases an excess of non-synonymous single nucleotide variants as well as a higher prevalence of gene-disruptive de novo mutations. We found four genes (LAMA2, DPYD, TRRAP and VPS39) affected by recurrent de novo events within or across the two populations, a finding unlikely to have occurred by chance. We show that de novo mutations affect genes with diverse functions and developmental profiles but we also find a substantial contribution of mutations in genes with higher expression in early fetal life. Our results help define the pattern of genomic and neural architecture of schizophrenia. PMID:23042115

  13. A Novel Strategy to Inhibit Hedgehog Signaling and Control Growth of Androgen-Independent Prostate Cancer Cells

    DTIC Science & Technology

    2013-12-01

    M TIME PPC1 Volume of Spheroid Ctrl (respective media) .2% DMSO 10 uM Free Curcumin 20 uM Free Curcumin 10 uM Tagged Curcumin 20 uM Tagged... Curcumin FIGURE 6 Ctrl media 10uM FC 20uM FC 20uM TC 10uM TC 2% DMSO PC3 t0 Div 8 FIGURE 7 Phospho-p65 NFκB subunit expression decreased In

  14. On Ensino da Astronomia no Ensino Médio sob Diferentes Abordagens Metodológicas

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Albrecht, Evonir

    2011-12-01

    O presente trabalho, sobre a intervenção de metodologias de ensino, foi desenvolvido na Escola Estadual Colônia dos Pescadores, na cidade de Caraguatatuba - SP, em três turmas do terceiro ano do Ensino Médio, perfazendo um total de 119 educandos, entre 16 e 19 anos. Antes de iniciar-se a intervenção, um questionário de vinte perguntas objetivas e dissertativas foi desenvolvido, aplicado pelo professor da classe, que ministrou as aulas correspondentes. Este questionário foi o mesmo em todas as três classes com o objetivo de diagnosticar o conhecimento prévio dos alunos sobre Astronomia. Começando a intervenção nas turmas, o professor envolvido usou três diferentes metodologias de ensino: (A) em forma de seminários, elaborados e apresentados pelos alunos, nos quais o professor fazia apenas as intervenções necessárias, (B) na forma tradicional, com a ajuda de multimídia para o desenvolvimento das aulas e a terceira (C) a tradicional, fazendo uso exclusivo de lousa e giz. No final do trabalho os alunos responderam o mesmo questionário novamente, de modo que os três métodos utilizados puderam ser comparados. Os resultados apresentados após a intervenção foram melhores que os resultados iniciais indicando a ocorrência de uma aprendizagem significativa. Quando os estudantes foram inicialmente questionados sobre quantos planetas existem no nosso sistema solar, a classe A obteve 39% de respostas certas, a classe B 48% e a classe C 46%, mas após o desenvolvimento das atividades, as classes obtiveram respectivamente 94%, 97 % e 90% de aproveitamento. No término do bimestre, foi sugerido aos educandos que elaborassem uma história em quadrinhos, a qual serviu para averiguar se os conceitos inicialmente observados foram alterados e se novos foram agregados. A análise das histórias foi dividida em três partes: Criatividade; Temas abordados; Emprego correto dos conceitos estudados. Ao final quatorze histórias foram confeccionadas. O aprendizado foi tão significativo que os alunos produzira m histórias em quadrinhos, com informações muito ricas. Outro dado muito importante é que, apesar da Astronomia ser um tema amplamente recomendado, não é ensinado nem em escolas de ensino fundamental nem no ensino médio.

  15. Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

    PubMed

    Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

    2015-02-01

    De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

  16. Genomic Context Analysis of de Novo STXBP1 Mutations Identifies Evidence of Splice Site DNA-Motif Associated Hotspots.

    PubMed

    Uddin, Mohammed; Woodbury-Smith, Marc; Chan, Ada J S; Albanna, Ammar; Minassian, Berge; Boelman, Cyrus; Scherer, Stephen W

    2018-03-28

    Mutations within STXBP1 have been associated with a range of neurodevelopmental disorders implicating the pleotropic impact of this gene. Although the frequency of de novo mutations within STXBP1 for selective cohorts with early onset epileptic encephalopathy is more than 1%, there is no evidence for a hotspot within the gene. In this study, we analyzed the genomic context of de novo STXBP1 mutations to examine whether certain motifs indicated a greater risk of mutation. Through a comprehensive context analysis of 136 de novo /rare mutation (SNV/Indels) sites in this gene, strikingly 26.92% of all SNV mutations occurred within 5bp upstream or downstream of a 'GTA' motif ( P < 0.0005). This implies a genomic context modulated mutagenesis. Moreover, 51.85% (14 out of 27) of the 'GTA' mutations are splicing compared to 14.70% (20 out of 136) of all reported mutations within STXBP1 We also noted that 11 of these 14 'GTA' associated mutations are de novo in origin. Our analysis provides strong evidence of DNA motif modulated mutagenesis for STXBP1 de novo splicing mutations. Copyright © 2018 Uddin et al.

  17. De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

    PubMed

    Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

    2018-05-01

    Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

  18. Incorporating metals into de novo proteins.

    PubMed

    Peacock, Anna F A

    2013-12-01

    The de novo design of artificial metalloproteins from first-principles is a powerful strategy with which to establish the minimum structure required for function, as well as to identify the important design features for tuning the chemistry of the coordinated metal ion. Herein we describe recent contributions to this field, covering metallo-porphyrin, mononuclear and multinuclear metal ion sites engineered into de novo proteins. Using miniature artificial scaffolds these examples demonstrate that complex natural protein folds are not required to mimic naturally occurring metal ion sites in proteins. More importantly progress is being made to engineer de novo metalloproteins capable of performing functions not in the repertoire of biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. De novo assembly of human genomes with massively parallel short read sequencing.

    PubMed

    Li, Ruiqiang; Zhu, Hongmei; Ruan, Jue; Qian, Wubin; Fang, Xiaodong; Shi, Zhongbin; Li, Yingrui; Li, Shengting; Shan, Gao; Kristiansen, Karsten; Li, Songgang; Yang, Huanming; Wang, Jian; Wang, Jun

    2010-02-01

    Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length sequences, making de novo assembly extremely challenging. Here, we describe a novel method for de novo assembly of large genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way.

  20. Attenuation of midinfrared free electron laser energy with eyewear

    NASA Astrophysics Data System (ADS)

    Joos, Karen M.; Gabella, William

    2005-04-01

    Purpose: To determine the attenuation of free electron laser (FEL) energy at several wavelengths through microscope objective and eyeglass lenses. Materials and Methods: The FEL at wavelengths of 2.3 um, 2.5 um, 3.0 um, 3.5 um, 4.0 um, 4.5 um, 5.0 um, 6.45 um, 7.0 um, 7.5 um, and 8.0 um was telescoped using a 500 mm nominal focal length lens and a 200 mm focal length lens. The beam had a final spot of about 3 mm and was passed through a 3 mm aperture and onto the 8 mm active area of a J9LP Molectron detector. The eyeglass sample was placed 3 cm in front of the detector. Energy readings were averaged over multiple pulses. Results: Attenuation varied greatly with wavelength and sample from a low attenuation of 0.46 dB, 90% transmission, for short wavelengths through common glass to greater than 60 dB attenuation (transmission at the detector noise level) for IR safe glass by Aura, Inc. Conclusion: Only the designated laser safety goggles effectively attenuate free electron laser energy at 2.3 um and 2.5 um. A microscope objective lens, polycarbonate, and silica glass eyewear is capable of effectively attenuating FEL energy at wavelengths greater than 4.5 um, but the polycarbonate lenses demonstrated material damage.

  1. Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly.

    PubMed

    Fritz-Laylin, Lillian K; Levy, Yaron Y; Levitan, Edward; Chen, Sean; Cande, W Zacheus; Lai, Elaine Y; Fulton, Chandler

    2016-03-01

    Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. © 2016 Wiley Periodicals, Inc.

  2. The importance of de novo mutations for pediatric neurological disease--It is not all in utero or birth trauma.

    PubMed

    Erickson, Robert P

    2016-01-01

    The advent of next generation sequencing (NGS, which consists of massively parallel sequencing to perform TGS (total genome sequencing) or WES (whole exome sequencing)) has abundantly discovered many causative mutations in patients with pediatric neurological disease. A surprisingly high number of these are de novo mutations which have not been inherited from either parent. For epilepsy, autism spectrum disorders, and neuromotor disorders, including cerebral palsy, initial estimates put the frequency of causative de novo mutations at about 15% and about 10% of these are somatic. There are some shared mutated genes between these three classes of disease. Studies of copy number variation by comparative genomic hybridization (CGH) proceded the NGS approaches but they also detect de novo variation which is especially important for ASDs. There are interesting differences between the mutated genes detected by CGS and NGS. In summary, de novo mutations cause a very significant proportion of pediatric neurological disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A framework for the interpretation of de novo mutation in human disease

    PubMed Central

    Samocha, Kaitlin E.; Robinson, Elise B.; Sanders, Stephan J.; Stevens, Christine; Sabo, Aniko; McGrath, Lauren M.; Kosmicki, Jack A.; Rehnström, Karola; Mallick, Swapan; Kirby, Andrew; Wall, Dennis P.; MacArthur, Daniel G.; Gabriel, Stacey B.; dePristo, Mark; Purcell, Shaun M.; Palotie, Aarno; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Gibbs, Richard A.; Schellenberg, Gerard D.; Sutcliffe, James S.; Devlin, Bernie; Roeder, Kathryn; Neale, Benjamin M.; Daly, Mark J.

    2014-01-01

    Spontaneously arising (‘de novo’) mutations play an important role in medical genetics. For diseases with extensive locus heterogeneity – such as autism spectrum disorders (ASDs) – the signal from de novo mutations (DNMs) is distributed across many genes, making it difficult to distinguish disease-relevant mutations from background variation. We provide a statistical framework for the analysis of DNM excesses per gene and gene set by calibrating a model of de novo mutation. We applied this framework to DNMs collected from 1,078 ASD trios and – while affirming a significant role for loss-of-function (LoF) mutations – found no excess of de novo LoF mutations in cases with IQ above 100, suggesting that the role of DNMs in ASD may reside in fundamental neurodevelopmental processes. We also used our model to identify ~1,000 genes that are significantly lacking functional coding variation in non-ASD samples and are enriched for de novo LoF mutations identified in ASD cases. PMID:25086666

  4. Direct Visualization of De novo Lipogenesis in Single Living Cells

    NASA Astrophysics Data System (ADS)

    Li, Junjie; Cheng, Ji-Xin

    2014-10-01

    Increased de novo lipogenesis is being increasingly recognized as a hallmark of cancer. Despite recent advances in fluorescence microscopy, autoradiography and mass spectrometry, direct observation of de novo lipogenesis in living systems remains to be challenging. Here, by coupling stimulated Raman scattering (SRS) microscopy with isotope labeled glucose, we were able to trace the dynamic metabolism of glucose in single living cells with high spatial-temporal resolution. As the first direct visualization, we observed that glucose was largely utilized for lipid synthesis in pancreatic cancer cells, which occurs at a much lower rate in immortalized normal pancreatic epithelial cells. By inhibition of glycolysis and fatty acid synthase (FAS), the key enzyme for fatty acid synthesis, we confirmed the deuterium labeled lipids in cancer cells were from de novo lipid synthesis. Interestingly, we also found that prostate cancer cells exhibit relatively lower level of de novo lipogenesis, but higher fatty acid uptake compared to pancreatic cancer cells. Together, our results demonstrate a valuable tool to study dynamic lipid metabolism in cancer and other disorders.

  5. Foldability of a Natural De Novo Evolved Protein.

    PubMed

    Bungard, Dixie; Copple, Jacob S; Yan, Jing; Chhun, Jimmy J; Kumirov, Vlad K; Foy, Scott G; Masel, Joanna; Wysocki, Vicki H; Cordes, Matthew H J

    2017-11-07

    The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. South African Guidelines Excellence (SAGE): Adopt, adapt, or contextualise?

    PubMed

    Dizon, J M; Grimmer, K; Louw, Q; Kredo, T; Young, T; Machingaidze, S

    2016-12-01

    Clinical practice guideline (CPG) activities must be planned carefully for efficient use of available resources and evidence-based implementation. De novo development of CPGs may sometimes 'recreate the wheel' and delay implementation. Three innovative alternatives to de novo CPG development (adopt, contextualise or adapt) are outlined, which have greater potential than de novo development to best use the limited available resources, personnel and time in settings such as South Africa.

  7. Suppression of polygalacturonase gene expression in the phytopathogenic fungus Ophiostoma novo-ulmi by RNA interference.

    PubMed

    Carneiro, Joyce S; de la Bastide, Paul Y; Chabot, Meghan; Lerch, Lindsey; Hintz, William E

    2010-05-01

    The fungal pathogen, Ophiostomo novo-ulmi, has been responsible for the rapid decline of American elm (Ulmus americana) across North America and remains a serious threat to surviving elm populations. The production of pectinolytic polygalacturonase enzymes has been implicated as a virulence factor for many fungal pathogens, including O. novo-ulmi. Previous work has shown that the targeted disruption of the endopolygalacturonase gene locus epg1 of O. novo-ulmi reduced, but did not eliminate pectinase activity. In the present study, we evaluated the use of RNA interference (RNAi) as a method of suppressing expression of the epg1 locus in O. novo-ulmi and compared its efficiency to the gene disruption method. While there was a reduction in epg1-specific mRNA transcripts and in the amount of polygalacturonase enzyme secreted for both methods of gene regulation, neither method completely suppressed the expression of pectinase activity. There was, however, a significantly greater reduction in both transcript levels and secreted enzyme observed for some of the RNAi transformants. As the first demonstration of RNAi in O. novo-ulmi, this method of gene regulation shows promise in future studies of gene expression and pathogenicity. Copyright 2010 Elsevier Inc. All rights reserved.

  8. The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo

    PubMed Central

    Gubala, Anna M.; Schmitz, Jonathan F.; Kearns, Michael J.; Vinh, Tery T.; Bornberg-Bauer, Erich; Wolfner, Mariana F.

    2017-01-01

    New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. PMID:28104747

  9. Precise detection of de novo single nucleotide variants in human genomes.

    PubMed

    Gómez-Romero, Laura; Palacios-Flores, Kim; Reyes, José; García, Delfino; Boege, Margareta; Dávila, Guillermo; Flores, Margarita; Schatz, Michael C; Palacios, Rafael

    2018-05-22

    The precise determination of de novo genetic variants has enormous implications across different fields of biology and medicine, particularly personalized medicine. Currently, de novo variations are identified by mapping sample reads from a parent-offspring trio to a reference genome, allowing for a certain degree of differences. While widely used, this approach often introduces false-positive (FP) results due to misaligned reads and mischaracterized sequencing errors. In a previous study, we developed an alternative approach to accurately identify single nucleotide variants (SNVs) using only perfect matches. However, this approach could be applied only to haploid regions of the genome and was computationally intensive. In this study, we present a unique approach, coverage-based single nucleotide variant identification (COBASI), which allows the exploration of the entire genome using second-generation short sequence reads without extensive computing requirements. COBASI identifies SNVs using changes in coverage of exactly matching unique substrings, and is particularly suited for pinpointing de novo SNVs. Unlike other approaches that require population frequencies across hundreds of samples to filter out any methodological biases, COBASI can be applied to detect de novo SNVs within isolated families. We demonstrate this capability through extensive simulation studies and by studying a parent-offspring trio we sequenced using short reads. Experimental validation of all 58 candidate de novo SNVs and a selection of non-de novo SNVs found in the trio confirmed zero FP calls. COBASI is available as open source at https://github.com/Laura-Gomez/COBASI for any researcher to use. Copyright © 2018 the Author(s). Published by PNAS.

  10. Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages.

    PubMed

    Rangel-Salazar, Rubén; Wickström-Lindholm, Marie; Aguilar-Salinas, Carlos A; Alvarado-Caudillo, Yolanda; Døssing, Kristina B V; Esteller, Manel; Labourier, Emmanuel; Lund, Gertrud; Nielsen, Finn C; Rodríguez-Ríos, Dalia; Solís-Martínez, Martha O; Wrobel, Katarzyna; Wrobel, Kazimierz; Zaina, Silvio

    2011-11-25

    We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

  11. Management, nutrition, and lactation performance are related to bulk tank milk de novo fatty acid concentration on northeastern US dairy farms.

    PubMed

    Woolpert, M E; Dann, H M; Cotanch, K W; Melilli, C; Chase, L E; Grant, R J; Barbano, D M

    2016-10-01

    This study investigated the relationship of management practices, dietary characteristics, milk composition, and lactation performance with de novo fatty acid (FA) concentration in bulk tank milk from commercial dairy farms with Holstein, Jersey, and mixed-breed cows. It was hypothesized that farms with higher de novo milk FA concentrations would more commonly use management and nutrition practices known to optimize ruminal conditions that enhance de novo synthesis of milk FA. Farms (n=44) located in Vermont and northeastern New York were selected based on a history of high de novo (HDN; 26.18±0.94g/100g of FA; mean ± standard deviation) or low de novo (LDN; 24.19±1.22g/100g of FA) FA in bulk tank milk. Management practices were assessed during one visit to each farm in March or April, 2014. Total mixed ration samples were collected and analyzed for chemical composition using near infrared spectroscopy. We found no differences in days in milk at the farm level. Yield of milk fat, true protein, and de novo FA per cow per day were higher for HDN versus LDN farms. The HDN farms had lower freestall stocking density (cows/stall) than LDN farms. Additionally, tiestall feeding frequency was higher for HDN than LDN farms. No differences between HDN and LDN farms were detected for dietary dry matter, crude protein, neutral detergent fiber, starch, or percentage of forage in the diet. However, dietary ether extract was lower for HDN than LDN farms. This research indicates that overcrowded freestalls, reduced feeding frequency, and greater dietary ether extract content are associated with lower de novo FA synthesis and reduced milk fat and true protein yields on commercial dairy farms. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. De novo glomerular diseases after renal transplantation: How is it different from recurrent glomerular diseases?

    PubMed Central

    Abbas, Fedaey; El Kossi, Mohsen; Jin, Jon Kim; Sharma, Ajay; Halawa, Ahmed

    2017-01-01

    The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the de novo glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. De novo membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. De novo C3 disease is rather rare. Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent. PMID:29312858

  13. Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

    PubMed

    O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

    2018-02-01

    Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

  14. De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

    PubMed

    Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin

    2016-08-01

    To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. De Novo Synthesized Estradiol Protects against Methylmercury-Induced Neurotoxicity in Cultured Rat Hippocampal Slices

    PubMed Central

    Ishihara, Yasuhiro; Komatsu, Shota; Munetsuna, Eiji; Onizaki, Masahiro; Ishida, Atsuhiko; Kawato, Suguru; Mukuda, Takao

    2013-01-01

    Background Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Methodology/Principal Findings Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Conclusions/Significance Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity. PMID:23405170

  16. The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo.

    PubMed

    Gubala, Anna M; Schmitz, Jonathan F; Kearns, Michael J; Vinh, Tery T; Bornberg-Bauer, Erich; Wolfner, Mariana F; Findlay, Geoffrey D

    2017-05-01

    New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.

    PubMed

    Stanik, Juraj; Dusatkova, Petra; Cinek, Ondrej; Valentinova, Lucia; Huckova, Miroslava; Skopkova, Martina; Dusatkova, Lenka; Stanikova, Daniela; Pura, Mikulas; Klimes, Iwar; Lebl, Jan; Gasperikova, Daniela; Pruhova, Stepanka

    2014-03-01

    MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A). Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing. Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo. In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.

  18. Prevalence and origin of De Novo duplications in Charcot-Marie-Tooth disease type 1A: First report of a De Novo duplication with a maternal origin

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

    Blair, I.P.; Nash, J.; Gordon, M.J.

    1996-03-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that {>=}10%more » of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus. 41 refs., 2 figs.« less

  19. De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up.

    PubMed

    Dannhorn, E; Cheung, M; Rodrigues, S; Cooper, H; Thorburn, D; Patch, D; Burroughs, A K; O'Beirne, J

    2014-12-01

    Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Particulated articular cartilage: CAIS and DeNovo NT.

    PubMed

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  1. Autism Spectrum Disorder

    MedlinePlus

    ... person’s cells, recent research has also shown that de novo , or spontaneous, gene mutations can influence the risk of developing autism spectrum disorder. De novo mutations are changes in sequences of deoxyribonucleic ...

  2. De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly.

    PubMed

    Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

    2015-11-26

    Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

  3. De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

    DTIC Science & Technology

    2014-08-01

    protein, and not FANCA , is required for the suppression of spontaneous de novo CNV. These findings support a model whereby the FANCD2 protein, possibly...cancer susceptibility gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have...the FA-BRCA pathway in the suppression of spontaneous de novo CNVs Task 1. Correction of FA-A, FA-C, and FA-D2 hTERT cells with pLenti6.2/V5- FANCA

  4. Studies on magnetocaloric and magnetic coupling effects =

    NASA Astrophysics Data System (ADS)

    Amaral, Joao Cunha de Sequeira

    O presente trabalho apresenta novas metodologias desenvolvidas para a analise das propriedades magneticas e magnetocaloricas de materiais, sustentadas em consideracoes teoricas a partir de modelos, nomeadamente a teoria de transicoes de fase de Landau, o modelo de campo medio molecular e a teoria de fenomeno critico. Sao propostos novos metodos de escala, permitindo a interpretacao de dados de magnetizacao de materiais numa perspectiva de campo medio molecular ou teoria de fenomeno critico. E apresentado um metodo de estimar a magnetizacao espontanea de um material ferromagnetico a partir de relacoes entropia/magnetizacao estabelecidas pelo modelo de campo medio molecular. A termodinamica das transicoes de fase magneticas de primeira ordem e estudada usando a teoria de Landau e de campo medio molecular (modelo de Bean-Rodbell), avaliando os efeitos de fenomenos fora de equilibrio e de condicoes de mistura de fase em estimativas do efeito magnetocalorico a partir de medidas magneticas. Efeitos de desordem, interpretados como uma distribuicao na interaccao magnetica entre ioes, estabelecem os efeitos de distribuicoes quimicas/estruturais nas propriedades magneticas e magnetocaloricas de materiais com transicoes de fase de segunda e de primeira ordem. O uso das metodologias apresentadas na interpretacao das propriedades magneticas de variados materiais ferromagneticos permitiu obter: 1) uma analise quantitativa da variacao de spin por iao Gadolinio devido a transicao estrutural do composto Gd5Si2Ge2, 2) a descricao da configuracao de cluster magnetico de ioes Mn na fase ferromagnetica em manganites da familia La-Sr e La-Ca, 3) a determinacao dos expoentes criticos β e δ do Niquel por metodos de escala, 4) a descricao do efeito da pressao nas propriedades magneticas e magnetocaloricas do composto LaFe11.5Si1.5 atraves do modelo de Bean-Rodbell, 5) uma estimativa da desordem em manganites ferromagneticas com transicoes de segunda e primeira ordem, 6) uma descricao de campo medio das propriedades magneticas da liga Fe23Cu77, 7) o estudo de efeitos de separacao de fase na familia de compostos La0.70-xErxSr0.30MnO3 e 8) a determinacao realista da variacao de entropia magnetica na familia de compostos de efeito magnetocalorico colossal Mn1-x-yFexCryAs.

  5. Work addiction and quality of life: a study with physicians.

    PubMed

    Azevedo, Walter Fernandes de; Mathias, Lígia Andrade da Silva Telles

    2017-01-01

    To evaluate the quality of life of physicians and investigate to what extent it is affected by work addiction. This is an exploratory, descriptive and cross-sectional study, conducted with 1,110 physicians. For data collection, we used a questionnaire with sociodemographic information, the World Health Organization Quality of Life BREF, and the Work Addiction Scale. Most physicians presented high quality of life. Female participants presented lower quality of life in the domains psychologic, environment and general (p<0.05). Quality of life was negatively correlated with the number of shifts (p<0.005). The higher the addiction to work, the lower the quality of life. The research allowed understanding the implications of work addiction in the quality of life. Further studies are required to support the development of strategies that improve health conditions and quality of life of medical professionals. Avaliar a qualidade de vida de médicos e investigar em que medida a adição ao trabalho a afeta. Trata-se de um estudo exploratório, descritivo e transversal, realizado com 1.110 médicos. Para coleta de dados, optou-se por utilizar um questionário contendo informações sociodemográficas, bem como aplicar o instrumento World Health Organization Quality of Life-BREF e a Escala de Adição ao Trabalho. Os médicos, em sua maioria, apresentaram alta qualidade de vida. Os participantes do sexo feminino tiveram menor qualidade de vida em relação aos homens nos domínios psicológico, meio ambiente e geral (p<0,05). A qualidade de vida correlacionou-se negativamente com o número de plantões (p<0,005), e quanto maior a adição ao trabalho, menor a qualidade de vida. A pesquisa permitiu o conhecimento das implicações da adição ao trabalho sobre a qualidade de vida. Novos estudos são necessários para subsidiar a elaboração de estratégias que melhorem a saúde e a qualidade de vida do profissional médico.

  6. 47 CFR 68.614 - Oppositions and appeals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... exhausted, the aggrieved party shall file its opposition with the Commission for de novo review. (b) As an alternative, oppositions to proposed technical criteria may be filed directly with the Commission for de novo...

  7. 47 CFR 68.614 - Oppositions and appeals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... exhausted, the aggrieved party shall file its opposition with the Commission for de novo review. (b) As an alternative, oppositions to proposed technical criteria may be filed directly with the Commission for de novo...

  8. The ascent of man(made oxidoreductases).

    PubMed

    Grayson, Katie J; Anderson, Jl Ross

    2018-05-10

    Though established 40 years ago, the field of de novo protein design has recently come of age, with new designs exhibiting an unprecedented level of sophistication in structure and function. With respect to catalysis, de novo enzymes promise to revolutionise the industrial production of useful chemicals and materials, while providing new biomolecules as plug-and-play components in the metabolic pathways of living cells. To this end, there are now de novo metalloenzymes that are assembled in vivo, including the recently reported C45 maquette, which can catalyse a variety of substrate oxidations with efficiencies rivalling those of closely related natural enzymes. Here we explore the successful design of this de novo enzyme, which was designed to minimise the undesirable complexity of natural proteins using a minimalistic bottom-up approach. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Shotgun Protein Sequencing with Meta-contig Assembly*

    PubMed Central

    Guthals, Adrian; Clauser, Karl R.; Bandeira, Nuno

    2012-01-01

    Full-length de novo sequencing from tandem mass (MS/MS) spectra of unknown proteins such as antibodies or proteins from organisms with unsequenced genomes remains a challenging open problem. Conventional algorithms designed to individually sequence each MS/MS spectrum are limited by incomplete peptide fragmentation or low signal to noise ratios and tend to result in short de novo sequences at low sequencing accuracy. Our shotgun protein sequencing (SPS) approach was developed to ameliorate these limitations by first finding groups of unidentified spectra from the same peptides (contigs) and then deriving a consensus de novo sequence for each assembled set of spectra (contig sequences). But whereas SPS enables much more accurate reconstruction of de novo sequences longer than can be recovered from individual MS/MS spectra, it still requires error-tolerant matching to homologous proteins to group smaller contig sequences into full-length protein sequences, thus limiting its effectiveness on sequences from poorly annotated proteins. Using low and high resolution CID and high resolution HCD MS/MS spectra, we address this limitation with a Meta-SPS algorithm designed to overlap and further assemble SPS contigs into Meta-SPS de novo contig sequences extending as long as 100 amino acids at over 97% accuracy without requiring any knowledge of homologous protein sequences. We demonstrate Meta-SPS using distinct MS/MS data sets obtained with separate enzymatic digestions and discuss how the remaining de novo sequencing limitations relate to MS/MS acquisition settings. PMID:22798278

  10. Shotgun protein sequencing with meta-contig assembly.

    PubMed

    Guthals, Adrian; Clauser, Karl R; Bandeira, Nuno

    2012-10-01

    Full-length de novo sequencing from tandem mass (MS/MS) spectra of unknown proteins such as antibodies or proteins from organisms with unsequenced genomes remains a challenging open problem. Conventional algorithms designed to individually sequence each MS/MS spectrum are limited by incomplete peptide fragmentation or low signal to noise ratios and tend to result in short de novo sequences at low sequencing accuracy. Our shotgun protein sequencing (SPS) approach was developed to ameliorate these limitations by first finding groups of unidentified spectra from the same peptides (contigs) and then deriving a consensus de novo sequence for each assembled set of spectra (contig sequences). But whereas SPS enables much more accurate reconstruction of de novo sequences longer than can be recovered from individual MS/MS spectra, it still requires error-tolerant matching to homologous proteins to group smaller contig sequences into full-length protein sequences, thus limiting its effectiveness on sequences from poorly annotated proteins. Using low and high resolution CID and high resolution HCD MS/MS spectra, we address this limitation with a Meta-SPS algorithm designed to overlap and further assemble SPS contigs into Meta-SPS de novo contig sequences extending as long as 100 amino acids at over 97% accuracy without requiring any knowledge of homologous protein sequences. We demonstrate Meta-SPS using distinct MS/MS data sets obtained with separate enzymatic digestions and discuss how the remaining de novo sequencing limitations relate to MS/MS acquisition settings.

  11. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

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

    Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp; Morales, Jorge; Fukai, Yoshihisa

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. Black-Right-Pointing-Pointer Disruption of the cpsII gene significantly reduced the growth of epimastigotes. Black-Right-Pointing-Pointer In particular, the CPSII-null mutant severely retarded intracellular growth. Black-Right-Pointing-Pointer The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediatemore » the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.« less

  12. Increased de novo copy number variants in the offspring of older males

    PubMed Central

    Flatscher-Bader, T; Foldi, C J; Chong, S; Whitelaw, E; Moser, R J; Burne, T H J; Eyles, D W; McGrath, J J

    2011-01-01

    The offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. In light of the evidence implicating copy number variants (CNVs) with schizophrenia and autism, we used a mouse model to explore the hypothesis that the offspring of older males have an increased risk of de novo CNVs. C57BL/6J sires that were 3- and 12–16-months old were mated with 3-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, 7 distinct CNVs were identified in a set of 12 offspring and their parents. Competitive quantitative PCR confirmed these CNVs in the original set and also established their frequency in an independent set of 77 offspring and their parents. On the basis of the combined samples, six de novo CNVs were detected in the offspring of older sires, whereas none were detected in the control group. Two of the CNVs were associated with behavioral and/or neuroanatomical phenotypic features. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. This is the first experimental demonstration that the offspring of older males have an increased risk of de novo CNVs. Our results support the hypothesis that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism by generation of de novo CNVs in the male germline. PMID:22832608

  13. Terminal sequence importance of de novo proteins from binary-patterned library: stable artificial proteins with 11- or 12-amino acid alphabet.

    PubMed

    Okura, Hiromichi; Takahashi, Tsuyoshi; Mihara, Hisakazu

    2012-06-01

    Successful approaches of de novo protein design suggest a great potential to create novel structural folds and to understand natural rules of protein folding. For these purposes, smaller and simpler de novo proteins have been developed. Here, we constructed smaller proteins by removing the terminal sequences from stable de novo vTAJ proteins and compared stabilities between mutant and original proteins. vTAJ proteins were screened from an α3β3 binary-patterned library which was designed with polar/ nonpolar periodicities of α-helix and β-sheet. vTAJ proteins have the additional terminal sequences due to the method of constructing the genetically repeated library sequences. By removing the parts of the sequences, we successfully obtained the stable smaller de novo protein mutants with fewer amino acid alphabets than the originals. However, these mutants showed the differences on ANS binding properties and stabilities against denaturant and pH change. The terminal sequences, which were designed just as flexible linkers not as secondary structure units, sufficiently affected these physicochemical details. This study showed implications for adjusting protein stabilities by designing N- and C-terminal sequences.

  14. Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature

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

    Ruiz, C.; Grubs, R.E.; Jewett, T.

    Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5,6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6,7, and 18 [six breaks]. The use of whole chromosome painting helpedmore » elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families. 38 refs., 3 figs., 4 tabs.« less

  15. De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome

    PubMed Central

    2013-01-01

    Background Molecular diagnostics can resolve locus heterogeneity underlying clinical phenotypes that may otherwise be co-assigned as a specific syndrome based on shared clinical features, and can associate phenotypically diverse diseases to a single locus through allelic affinity. Here we describe an apparently novel syndrome, likely caused by de novo truncating mutations in ASXL3, which shares characteristics with Bohring-Opitz syndrome, a disease associated with de novo truncating mutations in ASXL1. Methods We used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome. Results Using genome-wide sequencing, we identified heterozygous, de novo truncating mutations in ASXL3, a transcriptional repressor related to ASXL1, in four unrelated probands. We found that these probands shared similar phenotypes, including severe feeding difficulties, failure to thrive, and neurologic abnormalities with significant developmental delay. Further, they showed less phenotypic overlap with patients who had de novo truncating mutations in ASXL1. Conclusion We have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome. PMID:23383720

  16. Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale.

    PubMed

    Liu, Siyang; Huang, Shujia; Rao, Junhua; Ye, Weijian; Krogh, Anders; Wang, Jun

    2015-01-01

    Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.

  17. Genetics Home Reference: genetic epilepsy with febrile seizures plus

    MedlinePlus

    ... one affected parent . Other cases result from new (de novo) mutations in the gene and occur in ... family. Dravet syndrome is almost always caused by de novo mutations, although it can be inherited from ...

  18. Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

    PubMed

    Tay, Wei Lin; Loh, Wann Jia; Lee, Lianne Ai Ling; Chng, Chiaw Ling

    2017-01-01

    We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

  19. MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in Simplex Families

    DTIC Science & Technology

    2014-12-01

    facts that de novo CNVs rates are consistently high in SPX ASD (5.8%-10.2%) versus familial ASD (2-3%), we hypothesize that low-activity MTHFR 677T...allele leads to increase global DNA hypomethylation and consequently results in increased generation of de novo CNVs bringing about a higher risk for...developing sporadic cases of autism. We proposed to test 1) the association of MTHFR 677T allele with rate of ASD related de novo CNVs ; 2) the

  20. MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in Simplex Families. Revision

    DTIC Science & Technology

    2013-10-01

    that de novo CNVs rates are consistently high in SPX ASD (5.8%-10.2%) versus familial ASD (2-3%), we hypothesize that low-activity MTHFR 677T allele...leads to increase global DNA hypomethylation and consequently results in increased generation of de novo CNVs bringing about a higher risk for...developing sporadic cases of autism. We proposed to test 1) the association of MTHFR 677T allele with rate of ASD related de novo CNVs ; 2) the

  1. Optimizing highly noncoplanar VMAT trajectories: the NoVo method.

    PubMed

    Langhans, Marco; Unkelbach, Jan; Bortfeld, Thomas; Craft, David

    2018-01-16

    We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar trajectories. While the use of noncoplanar beam arrangements for intensity modulated radiation therapy (IMRT), and in particular high fraction stereotactic radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less common as the availability of treatment machines handling these is limited. For both IMRT and VMAT, the beam angle selection problem is highly nonconvex in nature, which is why automated beam angle selection procedures have not entered mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the simultaneous trajectories of the gantry and the couch) by first computing a [Formula: see text] solution (beams from every possible direction, suitably discretized) and then eliminating beams by examing fluence contributions. Also all beam angles are scored via geometrical considerations only to find out the usefulness of the whole beam space in a very short time. A custom path finding algorithm is applied to find an optimized, continuous trajectory through the most promising beam angles using the calculated score of the beam space. Finally, using this trajectory a VMAT plan is optimized. For three clinical cases, a lung, brain, and liver case, we compare NoVo to the ideal [Formula: see text] solution, nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar VMAT algorithm. NoVo comes closest to the [Formula: see text] solution considering the lung case (brain and liver case: second), as well as improving the solution time by using geometrical considerations, followed by a time effective iterative process reducing the [Formula: see text] solution. Compared to a recently published noncoplanar VMAT algorithm, using NoVo the computation time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung, brain and liver cases, respectively.

  2. Optimizing highly noncoplanar VMAT trajectories: the NoVo method

    NASA Astrophysics Data System (ADS)

    Langhans, Marco; Unkelbach, Jan; Bortfeld, Thomas; Craft, David

    2018-01-01

    We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar trajectories. While the use of noncoplanar beam arrangements for intensity modulated radiation therapy (IMRT), and in particular high fraction stereotactic radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less common as the availability of treatment machines handling these is limited. For both IMRT and VMAT, the beam angle selection problem is highly nonconvex in nature, which is why automated beam angle selection procedures have not entered mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the simultaneous trajectories of the gantry and the couch) by first computing a 4π solution (beams from every possible direction, suitably discretized) and then eliminating beams by examing fluence contributions. Also all beam angles are scored via geometrical considerations only to find out the usefulness of the whole beam space in a very short time. A custom path finding algorithm is applied to find an optimized, continuous trajectory through the most promising beam angles using the calculated score of the beam space. Finally, using this trajectory a VMAT plan is optimized. For three clinical cases, a lung, brain, and liver case, we compare NoVo to the ideal 4π solution, nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar VMAT algorithm. NoVo comes closest to the 4π solution considering the lung case (brain and liver case: second), as well as improving the solution time by using geometrical considerations, followed by a time effective iterative process reducing the 4π solution. Compared to a recently published noncoplanar VMAT algorithm, using NoVo the computation time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung, brain and liver cases, respectively.

  3. Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder?

    PubMed

    Kinney, Dennis K; Barch, Daniel H; Chayka, Bogdan; Napoleon, Siena; Munir, Kerim M

    2010-01-01

    Recent research has discovered that a number of genetic risk factors for autism are de novo mutations. Advanced parental age at the time of conception is associated with increased risk for both autism and de novo mutations. We investigated the hypothesis that other environmental factors associated with increased risk for autism might also be mutagenic and contribute to autism by causing de novo mutations. A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors--mercury, cadmium, nickel, trichloroethylene, and vinyl chloride--are established mutagens. Another four--including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation--are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress--a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA. We note how de novo mutations may also help explain why the concordance rate for autism is so markedly higher in monozygotic than dizygotic twins. De novo mutations may also explain in part why the prevalence of autism is so remarkably high, given the evidence for a strong role of genetic factors and the low fertility of individuals with autism--and resultant selection pressure against autism susceptibility genes. These several lines of evidence provide support for the hypothesis, and warrant new research approaches--which we suggest--to address limitations in existing studies. The hypothesis has implications for understanding possible etiologic roles of de novo mutations in autism, and it suggests possible approaches to primary prevention of the disorder, such as addressing widespread vitamin D deficiency and exposure to known mutagens.

  4. 76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... and Radiological Health (CDRH) guidance documents is available at http://www.fda.gov/MedicalDevices... ``De Novo Classification Process (Evaluation of Automatic Class III Designation)'' from CDRH you may...

  5. Disulfiram-induced de novo seizures in the absence of ethanol challenge.

    PubMed

    McConchie, R D; Panitz, D R; Sauber, S R; Shapiro, S

    1983-07-01

    The literature on disulfiram-associated seizures is reviewed. A case report of a disulfiram-induced de novo seizure in a 35-year-old man is presented. Possible mechanisms of seizure facilitation are discussed.

  6. De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly

    PubMed Central

    Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

    2015-01-01

    Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm. DOI: http://dx.doi.org/10.7554/eLife.10586.001 PMID:26609813

  7. Serine hydroxymethyltransferase anchors de novo thymidylate synthesis pathway to nuclear lamina for DNA synthesis.

    PubMed

    Anderson, Donald D; Woeller, Collynn F; Chiang, En-Pei; Shane, Barry; Stover, Patrick J

    2012-03-02

    The de novo thymidylate biosynthetic pathway in mammalian cells translocates to the nucleus for DNA replication and repair and consists of the enzymes serine hydroxymethyltransferase 1 and 2α (SHMT1 and SHMT2α), thymidylate synthase, and dihydrofolate reductase. In this study, we demonstrate that this pathway forms a multienzyme complex that is associated with the nuclear lamina. SHMT1 or SHMT2α is required for co-localization of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, indicating that SHMT serves as scaffold protein that is essential for complex formation. The metabolic complex is enriched at sites of DNA replication initiation and associated with proliferating cell nuclear antigen and other components of the DNA replication machinery. These data provide a mechanism for previous studies demonstrating that SHMT expression is rate-limiting for de novo thymidylate synthesis and indicate that de novo thymidylate biosynthesis occurs at replication forks.

  8. Lethal Ultra-Early Subarachnoid Hemorrhage Due to Rupture of De Novo Aneurysm 5 Months After Primary Aneurysmatic Subarachnoid Hemorrhage.

    PubMed

    Walter, Johannes; Unterberg, Andreas W; Zweckberger, Klaus

    2018-05-01

    Approximately 1% of all patients surviving rupture of a cerebral aneurysm suffer from a second aneurysmatic subarachnoid hemorrhage later in their lives, 61% of which are caused by rupture of a de novo aneurysm. Latency between bleedings is usually many years, and younger patients tend to achieve better outcomes from a second subarachnoid hemorrhage. We report an unusual case of lethal ultra-early rupture of a de novo aneurysm of the anterior communicating artery only 5 months after the initial subarachnoid hemorrhage and complete coiling in a young, healthy male patient. Despite complete aneurysm obliteration, young age, and good recovery, patients may be subjected to secondary subarachnoid hemorrhages from de novo aneurysms after only a few months of the initial bleeding. Early-control magnetic resonance angiography might hence be advisable. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Installing hydrolytic activity into a completely de novo protein framework

    NASA Astrophysics Data System (ADS)

    Burton, Antony J.; Thomson, Andrew R.; Dawson, William M.; Brady, R. Leo; Woolfson, Derek N.

    2016-09-01

    The design of enzyme-like catalysts tests our understanding of sequence-to-structure/function relationships in proteins. Here we install hydrolytic activity predictably into a completely de novo and thermostable α-helical barrel, which comprises seven helices arranged around an accessible channel. We show that the lumen of the barrel accepts 21 mutations to functional polar residues. The resulting variant, which has cysteine-histidine-glutamic acid triads on each helix, hydrolyses p-nitrophenyl acetate with catalytic efficiencies that match the most-efficient redesigned hydrolases based on natural protein scaffolds. This is the first report of a functional catalytic triad engineered into a de novo protein framework. The flexibility of our system also allows the facile incorporation of unnatural side chains to improve activity and probe the catalytic mechanism. Such a predictable and robust construction of truly de novo biocatalysts holds promise for applications in chemical and biochemical synthesis.

  10. DE NOVO MUTATIONS IN AUTISM IMPLICATE THE SYNAPTIC ELIMINATION NETWORK.

    PubMed

    Ram Venkataraman, Guhan; O'Connell, Chloe; Egawa, Fumiko; Kashef-Haghighi, Dorna; Wall, Dennis P

    2017-01-01

    Autism has been shown to have a major genetic risk component; the architecture of documented autism in families has been over and again shown to be passed down for generations. While inherited risk plays an important role in the autistic nature of children, de novo (germline) mutations have also been implicated in autism risk. Here we find that autism de novo variants verified and published in the literature are Bonferroni-significantly enriched in a gene set implicated in synaptic elimination. Additionally, several of the genes in this synaptic elimination set that were enriched in protein-protein interactions (CACNA1C, SHANK2, SYNGAP1, NLGN3, NRXN1, and PTEN) have been previously confirmed as genes that confer risk for the disorder. The results demonstrate that autism-associated de novos are linked to proper synaptic pruning and density, hinting at the etiology of autism and suggesting pathophysiology for downstream correction and treatment.

  11. De Novo Synthesis of Mono- and Oligosaccharides via Dihydropyran Intermediates.

    PubMed

    Song, Wangze; Wang, Shuojin; Tang, Weiping

    2017-05-18

    The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most chemical syntheses in this area focus on the preparation of carbohydrates from naturally occurring monosaccharides. De novo chemical synthesis of carbohydrates from feedstock starting materials has emerged as a complementary method for the preparation of diverse mono- and oligosaccharides. In this review, the history of de novo carbohydrate synthesis is briefly discussed and particular attention is given to methods that address the formation of glycosidic bonds for potential de novo synthesis of oligosaccharides. Almost all methods of this kind involve the formation of dihydropyran intermediates. Recent progress in forming dihydropyrans by Achmatowicz rearrangement, hetero-Diels-Alder cycloaddition, ring-closing metathesis, and other methods is also elaborated. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Proteomic characterization of the outer membrane vesicle of the halophilic marine bacterium Novosphingobium pentaromativorans US6-1.

    PubMed

    Yun, Sung Ho; Lee, Sang-Yeop; Choi, Chi-Won; Lee, Hayoung; Ro, Hyun-Joo; Jun, Sangmi; Kwon, Yong Min; Kwon, Kae Kyoung; Kim, Sang-Jin; Kim, Gun-Hwa; Kim, Seung Il

    2017-01-01

    Novosphingobium pentaromativorans US6-1 is a Gram-negative halophilic marine bacterium able to utilize several polycyclic aromatic hydrocarbons such as phenanthrene, pyrene, and benzo[a]pyrene. In this study, using transmission electron microscopy, we confirmed that N. pentaromativorans US6-1 produces outer membrane vesicles (OMVs). N. pentaromativorans OMVs (hereafter OMV Novo ) are spherical in shape, and the average diameter of OMV Novo is 25-70 nm. Proteomic analysis revealed that outer membrane proteins and periplasmic proteins of N. pentaromativorans are the major protein components of OMV Novo . Comparative proteomic analysis with the membrane-associated protein fraction and correlation analysis demonstrated that the outer membrane proteins of OMV Novo originated from the membrane- associated protein fraction. To the best of our knowledge, this study is the first to characterize OMV purified from halophilic marine bacteria.

  13. A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

    PubMed

    Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

    2016-08-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

  14. BME Estimation of Residential Exposure to Ambient PM10 and Ozone at Multiple Time Scales

    PubMed Central

    Yu, Hwa-Lung; Chen, Jiu-Chiuan; Christakos, George; Jerrett, Michael

    2009-01-01

    Background Long-term human exposure to ambient pollutants can be an important contributing or etiologic factor of many chronic diseases. Spatiotemporal estimation (mapping) of long-term exposure at residential areas based on field observations recorded in the U.S. Environmental Protection Agency’s Air Quality System often suffer from missing data issues due to the scarce monitoring network across space and the inconsistent recording periods at different monitors. Objective We developed and compared two upscaling methods: UM1 (data aggregation followed by exposure estimation) and UM2 (exposure estimation followed by data aggregation) for the long-term PM10 (particulate matter with aerodynamic diameter ≤ 10 μm) and ozone exposure estimations and applied them in multiple time scales to estimate PM and ozone exposures for the residential areas of the Health Effects of Air Pollution on Lupus (HEAPL) study. Method We used Bayesian maximum entropy (BME) analysis for the two upscaling methods. We performed spatiotemporal cross-validations at multiple time scales by UM1 and UM2 to assess the estimation accuracy across space and time. Results Compared with the kriging method, the integration of soft information by the BME method can effectively increase the estimation accuracy for both pollutants. The spatiotemporal distributions of estimation errors from UM1 and UM2 were similar. The cross-validation results indicated that UM2 is generally better than UM1 in exposure estimations at multiple time scales in terms of predictive accuracy and lack of bias. For yearly PM10 estimations, both approaches have comparable performance, but the implementation of UM1 is associated with much lower computation burden. Conclusion BME-based upscaling methods UM1 and UM2 can assimilate core and site-specific knowledge bases of different formats for long-term exposure estimation. This study shows that UM1 can perform reasonably well when the aggregation process does not alter the spatiotemporal structure of the original data set; otherwise, UM2 is preferable. PMID:19440491

  15. 78 FR 9051 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... Corporation, Sturgeon Bay, Wisconsin; to engage de novo through its subsidiary, Admiral Asset Management, LLC... novo, or to acquire or control voting securities or assets of a company, including the companies listed...

  16. Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

    PubMed

    Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

    2017-01-01

    Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

  17. Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize.

    PubMed

    Liu, Yalin; Su, Handong; Pang, Junling; Gao, Zhi; Wang, Xiu-Jie; Birchler, James A; Han, Fangpu

    2015-03-17

    The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity.

  18. Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize

    PubMed Central

    Liu, Yalin; Su, Handong; Pang, Junling; Gao, Zhi; Wang, Xiu-Jie; Birchler, James A.; Han, Fangpu

    2015-01-01

    The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity. PMID:25733907

  19. The concept of template-based de novo design from drug-derived molecular fragments and its application to TAR RNA.

    PubMed

    Schüller, Andreas; Suhartono, Marcel; Fechner, Uli; Tanrikulu, Yusuf; Breitung, Sven; Scheffer, Ute; Göbel, Michael W; Schneider, Gisbert

    2008-02-01

    Principles of fragment-based molecular design are presented and discussed in the context of de novo drug design. The underlying idea is to dissect known drug molecules in fragments by straightforward pseudo-retro-synthesis. The resulting building blocks are then used for automated assembly of new molecules. A particular question has been whether this approach is actually able to perform scaffold-hopping. A prospective case study illustrates the usefulness of fragment-based de novo design for finding new scaffolds. We were able to identify a novel ligand disrupting the interaction between the Tat peptide and TAR RNA, which is part of the human immunodeficiency virus (HIV-1) mRNA. Using a single template structure (acetylpromazine) as reference molecule and a topological pharmacophore descriptor (CATS), new chemotypes were automatically generated by our de novo design software Flux. Flux features an evolutionary algorithm for fragment-based compound assembly and optimization. Pharmacophore superimposition and docking into the target RNA suggest perfect matching between the template molecule and the designed compound. Chemical synthesis was straightforward, and bioactivity of the designed molecule was confirmed in a FRET assay. This study demonstrates the practicability of de novo design to generating RNA ligands containing novel molecular scaffolds.

  20. The present and future of de novo whole-genome assembly.

    PubMed

    Sohn, Jang-Il; Nam, Jin-Wu

    2018-01-01

    As the advent of next-generation sequencing (NGS) technology, various de novo assembly algorithms based on the de Bruijn graph have been developed to construct chromosome-level sequences. However, numerous technical or computational challenges in de novo assembly still remain, although many bright ideas and heuristics have been suggested to tackle the challenges in both experimental and computational settings. In this review, we categorize de novo assemblers on the basis of the type of de Bruijn graphs (Hamiltonian and Eulerian) and discuss the challenges of de novo assembly for short NGS reads regarding computational complexity and assembly ambiguity. Then, we discuss how the limitations of the short reads can be overcome by using a single-molecule sequencing platform that generates long reads of up to several kilobases. In fact, the long read assembly has caused a paradigm shift in whole-genome assembly in terms of algorithms and supporting steps. We also summarize (i) hybrid assemblies using both short and long reads and (ii) overlap-based assemblies for long reads and discuss their challenges and future prospects. This review provides guidelines to determine the optimal approach for a given input data type, computational budget or genome. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. An accurate binding interaction model in de novo computational protein design of interactions: if you build it, they will bind.

    PubMed

    London, Nir; Ambroggio, Xavier

    2014-02-01

    Computational protein design efforts aim to create novel proteins and functions in an automated manner and, in the process, these efforts shed light on the factors shaping natural proteins. The focus of these efforts has progressed from the interior of proteins to their surface and the design of functions, such as binding or catalysis. Here we examine progress in the development of robust methods for the computational design of non-natural interactions between proteins and molecular targets such as other proteins or small molecules. This problem is referred to as the de novo computational design of interactions. Recent successful efforts in de novo enzyme design and the de novo design of protein-protein interactions open a path towards solving this problem. We examine the common themes in these efforts, and review recent studies aimed at understanding the nature of successes and failures in the de novo computational design of interactions. While several approaches culminated in success, the use of a well-defined structural model for a specific binding interaction in particular has emerged as a key strategy for a successful design, and is therefore reviewed with special consideration. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    PubMed Central

    Stellaard, Frans

    2017-01-01

    The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. PMID:28321334

  3. A Hybrid Parallel Strategy Based on String Graph Theory to Improve De Novo DNA Assembly on the TianHe-2 Supercomputer.

    PubMed

    Zhang, Feng; Liao, Xiangke; Peng, Shaoliang; Cui, Yingbo; Wang, Bingqiang; Zhu, Xiaoqian; Liu, Jie

    2016-06-01

    ' The de novo assembly of DNA sequences is increasingly important for biological researches in the genomic era. After more than one decade since the Human Genome Project, some challenges still exist and new solutions are being explored to improve de novo assembly of genomes. String graph assembler (SGA), based on the string graph theory, is a new method/tool developed to address the challenges. In this paper, based on an in-depth analysis of SGA we prove that the SGA-based sequence de novo assembly is an NP-complete problem. According to our analysis, SGA outperforms other similar methods/tools in memory consumption, but costs much more time, of which 60-70 % is spent on the index construction. Upon this analysis, we introduce a hybrid parallel optimization algorithm and implement this algorithm in the TianHe-2's parallel framework. Simulations are performed with different datasets. For data of small size the optimized solution is 3.06 times faster than before, and for data of middle size it's 1.60 times. The results demonstrate an evident performance improvement, with the linear scalability for parallel FM-index construction. This results thus contribute significantly to improving the efficiency of de novo assembly of DNA sequences.

  4. De Novo Sphingolipid Synthesis Is Essential for Viability, but Not for Transport of Glycosylphosphatidylinositol-Anchored Proteins, in African Trypanosomes▿

    PubMed Central

    Sutterwala, Shaheen S.; Creswell, Caleb H.; Sanyal, Sumana; Menon, Anant K.; Bangs, James D.

    2007-01-01

    De novo sphingolipid synthesis is required for the exit of glycosylphosphatidylinositol (GPI)-anchored membrane proteins from the endoplasmic reticulum in yeast. Using a pharmacological approach, we test the generality of this phenomenon by analyzing the transport of GPI-anchored cargo in widely divergent eukaryotic systems represented by African trypanosomes and HeLa cells. Myriocin, which blocks the first step of sphingolipid synthesis (serine + palmitate → 3-ketodihydrosphingosine), inhibited the growth of cultured bloodstream parasites, and growth was rescued with exogenous 3-ketodihydrosphingosine. Myriocin also blocked metabolic incorporation of [3H]serine into base-resistant sphingolipids. Biochemical analyses indicate that the radiolabeled lipids are not sphingomyelin or inositol phosphorylceramide, suggesting that bloodstream trypanosomes synthesize novel sphingolipids. Inhibition of de novo sphingolipid synthesis with myriocin had no adverse effect on either general secretory trafficking or GPI-dependent trafficking in trypanosomes, and similar results were obtained with HeLa cells. A mild effect on endocytosis was seen for bloodstream trypanosomes after prolonged incubation with myriocin. These results indicate that de novo synthesis of sphingolipids is not a general requirement for secretory trafficking in eukaryotic cells. However, in contrast to the closely related kinetoplastid Leishmania major, de novo sphingolipid synthesis is essential for the viability of bloodstream-stage African trypanosomes. PMID:17220466

  5. Endogenous Hot Spots of De Novo Telomere Addition in the Yeast Genome Contain Proximal Enhancers That Bind Cdc13

    PubMed Central

    Obodo, Udochukwu C.; Epum, Esther A.; Platts, Margaret H.; Seloff, Jacob; Dahlson, Nicole A.; Velkovsky, Stoycho M.; Paul, Shira R.

    2016-01-01

    DNA double-strand breaks (DSBs) pose a threat to genome stability and are repaired through multiple mechanisms. Rarely, telomerase, the enzyme that maintains telomeres, acts upon a DSB in a mutagenic process termed telomere healing. The probability of telomere addition is increased at specific genomic sequences termed sites of repair-associated telomere addition (SiRTAs). By monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX share a bipartite structure in which a core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances the probability of de novo telomere formation. The Stim and Core sequences are sufficient to confer a high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded DNA binding protein that recruits telomerase to endogenous telomeres, is known to stimulate de novo telomere addition when artificially recruited to an induced DSB. Here we show that the ability of the Stim sequence to enhance de novo telomere addition correlates with its ability to bind Cdc13, indicating that natural sites at which telomere addition occurs at high frequency require binding by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition. PMID:27044869

  6. Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

    PubMed Central

    Gravells, P; Hoh, L; Canovas, D; Rennie, I G; Sisley, K; Bryant, H E

    2011-01-01

    Background: Uveal melanoma (UM) is the most common primary intraocular tumour of adults, frequently metastasising to the liver. Hepatic metastases are difficult to treat and are mainly unresponsive to chemotherapy. To investigate why UM are so chemo-resistant we explored the effect of interstrand cross-linking agents mitomycin C (MMC) and cisplatin in comparison with hydroxyurea (HU). Methods: Sensitivity to MMC, cisplatin and HU was tested in established UM cell lines using clonogenic assays. The response of UM to MMC was confirmed in MTT assays using short-term cultures of primary UM. The expression of cytochrome P450 reductase (CYP450R) was analysed by western blotting, and DNA cross-linking was assessed using COMET analysis supported by γ-H2AX foci formation. Results: Both established cell lines and primary cultures of UM were resistant to the cross-linking agent MMC (in each case P<0.001 in Student's t-test compared with controls). In two established UM cell lines, DNA cross-link damage was not induced by MMC (in both cases P<0.05 in Students's t-test compared with damage induced in controls). In all, 6 out of 6 UMs tested displayed reduced expression of the metabolising enzyme CYP450R and transient expression of CYP450R increased MMC sensitivity of UM. Conclusion: We suggest that reduced expression of CYP450R is responsible for MMC resistance of UM, through a lack of bioactivation, which can be reversed by complementing UM cell lines with CYP450R. PMID:21386838

  7. Brazilian guidelines for the diagnosis and treatment of cystic fibrosis.

    PubMed

    Athanazio, Rodrigo Abensur; Silva Filho, Luiz Vicente Ribeiro Ferreira da; Vergara, Alberto Andrade; Ribeiro, Antônio Fernando; Riedi, Carlos Antônio; Procianoy, Elenara da Fonseca Andrade; Adde, Fabíola Villac; Reis, Francisco José Caldeira; Ribeiro, José Dirceu; Torres, Lídia Alice; Fuccio, Marcelo Bicalho de; Epifanio, Matias; Firmida, Mônica de Cássia; Damaceno, Neiva; Ludwig-Neto, Norberto; Maróstica, Paulo José Cauduro; Rached, Samia Zahi; Melo, Suzana Fonseca de Oliveira

    2017-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression) and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions. RESUMO A fibrose cística (FC) é uma doença genética autossômica recessiva caracterizada pela disfunção do gene CFTR. Trata-se de uma doença multissistêmica que ocorre mais frequentemente em populações descendentes de caucasianos. Nas últimas décadas, diversos avanços no diagnóstico e tratamento da FC mudaram drasticamente o cenário dessa doença, com aumento expressivo da sobrevida e qualidade de vida. Atualmente, o Brasil dispõe de um programa de ampla cobertura para a triagem neonatal de FC e centros de referência distribuídos na maior parte desses estados para seguimento dos indivíduos. Antigamente confinada à faixa etária pediátrica, tem-se observado um aumento de pacientes adultos com FC tanto pelo maior número de diagnósticos de formas atípicas, de expressão fenotípica mais leve, assim como pelo aumento da expectativa de vida com os novos tratamentos. Entretanto, ainda se observa uma grande heterogeneidade no acesso aos métodos diagnósticos e terapêuticos para FC entre as diferentes regiões brasileiras. O objetivo dessas diretrizes foi reunir as principais evidências científicas que norteiam o manejo desses pacientes. Um grupo de 18 especialistas em FC elaborou 82 perguntas clínicas relevantes que foram divididas em cinco categorias: características de um centro de referência; diagnóstico; tratamento da doença respiratória; tratamento gastrointestinal e nutricional; e outros aspectos. Diversos profissionais brasileiros atuantes na área da FC foram convidados a responder as perguntas formuladas pelos coordenadores. A literatura disponível foi pesquisada na base de dados PubMed com palavras-chave, buscando-se as melhores respostas às perguntas dos autores.

  8. LAPAROSCOPICALLY ASSISTED ANORECTOPLASTY AND THE USE OF THE BIPOLAR DEVICE TO SEAL THE RECTAL URINARY FISTULA.

    PubMed

    Dutra, Robson Azevedo; Boscollo, Adriana Cartafina Perez

    2016-01-01

    The anorectal anomalies consist in a complex group of birth defects. Laparoscopic-assisted anorectoplasty improved visualization of the rectal fistula and the ability to place the pull-through segment within the elevator muscle complex with minimal dissection. There is no consensus on how the fistula should be managed. To evaluate the laparoscopic-assisted anorectoplasty and the treatment of the rectal urinary fistula by a bipolar sealing device. It was performed according to the original description by Georgeson1. Was used 10 mm infraumbilical access portal for 30º optics. The pneumoperitoneum was established with pressure 8-10 cm H2O. Two additional trocars of 5 mm were placed on the right and left of the umbilicus. The dissection started on peritoneal reflection using Ligasure(r). With the reduction in the diameter of the distal rectum was identified the fistula to the urinary tract. The location of the new anus was defined by the location of the external anal sphincter muscle complex, using electro muscle stimulator externally. Finally, it was made an anastomosis between the rectum and the new location of the anus. A Foley urethral probe was left for seven days. Seven males were operated, six with rectoprostatic and one with rectovesical fistula. The follow-up period ranged from one to four years. The last two patients operated underwent bipolar sealing of the fistula between the rectum and urethra without sutures or surgical ligation. No evidence of urethral leaks was identified. There are benefits of the laparoscopic-assisted anorectoplasty for the treatment of anorectal anomaly. The use of a bipolar energy source that seals the rectal urinary fistula has provided a significant decrease in the operating time and made the procedure be more elegant. As anomalias anorretais consistem de um grupo complexo de defeitos congênitos. A anorretoplastia laparoscópica permite melhor visualização da fístula retourinária e propicia o posicionamento do reto abaixado dentro do complexo muscular do elevador do ânus com mínima dissecção. Não há consenso na literatura sobre o melhor tratamento dessa fístula. Avaliar a anorretoplastia laparoscópica e o selamento bipolar da fístula retourinária. Ela foi realizada de acordo com a descrição original de Georgeson1. Utilizou-se o acesso infraumbilical com portal de 10 mm para a ótica de 30º. O pneumoperitônio foi estabelecido com pressão de 8-10 cm de H2O. Dois trocárteres adicionais de 5 mm foram colocados à direita e à esquerda da cicatriz umbilical. A dissecção foi iniciada na reflexão peritoneal usando Ligasure(r). Com a redução do calibre do reto distalmente, foi identificada a fístula para a o trato urinário. O local do novo ânus foi definido por meio da localização do complexo muscular do esfíncter anal externo, utilizando-se estimulador eletro muscular externamente. Por fim, foi confeccionada uma anastomose entre o reto e o novo local do ânus. Uma sonda uretral de Foley foi deixada durante sete dias. Sete meninos foram operados, seis com fístula retoprostática e um retovesical. O período de seguimento variou de um a quatro anos. Os dois últimos pacientes operados foram submetidos ao selamento bipolar da fístula entre o reto e a uretra, sem suturas ou ligadura cirúrgica com pontos. No seguimento em longo prazo não houve evidências de fístulas urinárias. Há benefícios da anorretoplastia laparoscópica para o tratamento de anomalia anorretal. O uso de uma fonte de energia bipolar que promova o selamento da fístula retourinária propiciou redução significativa do tempo cirúrgico e tornou o procedimento mais elegante.

  9. Tuberculosis recurrence in a priority city in the state of São Paulo, Brazil.

    PubMed

    Vieira, Amadeu Antonio; Leite, Danila Torres; Adreoni, Solange

    2017-01-01

    To describe cases of tuberculosis recurrence (TBR), stratified by temporal classification (early or late TBR), and to identify possible predictors of such recurrence. This was an analytical retrospective observational epidemiological study involving a cohort of 963 new cases of pulmonary tuberculosis, reported and treated via the Tuberculosis Control Program in the city of Carapicuíba, Brazil. The study period was from 2000 to 2010. All of the pulmonary tuberculosis patients who successfully completed the treatment (with or without confirmation of cure) were selected and followed until December 31, 2012. Of the 963 cases, TBR occurred in 47 (4.88%). The mean time between the first and second tuberculosis episodes was 36.12 months. Of the 47 TBR cases, 16 (34.04%) occurred within the first 18 months after the completion of the initial treatment (early TBR) and 31 (65.96%) occurred thereafter (late TBR). There were statistically significant differences between the early and late TBR groups only regarding level of education (≤ 3 vs. > 3 years of schooling; p < 0.004) and weight gain at completion of the initial treatment (1.78 kg vs. 5.31 kg; p < 0.045)-not regarding any of the other variables studied. A low level of education might translate to poor treatment adherence, which impedes the killing of bacilli and facilitates their survival in a latent state, making it appear as if the treatment was effective. Minimal or no weight gain at completion of the initial treatment might be a reliable biomarker to be used by health care facilities that provide tuberculosis treatment. Descrever os casos de recorrência de tuberculose (RTB) e identificar possíveis preditores segundo a classificação RTB recente ou tardia. Estudo epidemiológico observacional analítico retrospectivo a partir de uma coorte de 963 casos novos de tuberculose pulmonar notificados e tratados no Programa de Controle de Tuberculose de Carapicuíba (SP). O período de estudo foi de 2000 a 2010. Todos os casos novos de tuberculose pulmonar que completaram com sucesso o tratamento (com ou sem cura confirmada) foram selecionados e seguidos até 31 de dezembro de 2012. Dos 963 casos, RTB ocorreu em 47 (4,88%). O tempo médio transcorrido até o segundo episódio foi de 36,12 meses. Dos 47 casos de RTB, 16 (34,04%) ocorreram em até 18 meses da alta do primeiro tratamento (RTB recente), e 31 (65,96%) ocorreram após 18 meses (RTB tardia). Entre as variáveis investigadas, somente houve diferenças significativas entre os grupos RTB recente e tardia em relação ao ganho de peso na alta do primeiro tratamento (1,78 kg vs. 5,31 kg; p < 0,045) e nível de escolaridade (≤ 3 vs. > 3 anos de estudo; p < 0,004). A baixa escolaridade pode indicar uma menor adesão ao tratamento, dificultando a esterilização dos bacilos e facilitando sua sobrevivência em forma dormente, o que mascara a efetividade do tratamento. A ausência ou um reduzido aumento de peso na alta do tratamento poderá servir como um marcador biológico que pode ser utilizado pelos serviços de saúde que realizam o tratamento de tuberculose.

  10. Construction of proteins with molecular recognition capabilities using α3β3 de novo protein scaffolds.

    PubMed

    Okura, Hiromichi; Mihara, Hisakazu; Takahashi, Tsuyoshi

    2013-10-01

    The molecular recognition ability of proteins is essential in biological systems, and therefore a considerable amount of effort has been devoted to constructing desired target-binding proteins using a variety of naturally occurring proteins as scaffolds. However, since generating a binding site in a native protein can often affect its structural properties, highly stable de novo protein scaffolds may be more amenable than the native proteins. We previously reported the generation of de novo proteins comprising three α-helices and three β-strands (α3β3) from a genetic library coding simplified amino acid sets. Two α3β3 de novo proteins, vTAJ13 and vTAJ36, fold into a native-like stable and molten globule-like structures, respectively, even though the proteins have similar amino acid compositions. Here, we attempted to create binding sites for the vTAJ13 and vTAJ36 proteins to prove the utility of de novo designed artificial proteins as a molecular recognition tool. Randomization of six amino acids at two linker sites of vTAJ13 and vTAJ36 followed by biopanning generated binding proteins that recognize the target molecules, fluorescein and green fluorescent protein, with affinities of 10(-7)-10(-8) M. Of note, the selected proteins from the vTAJ13-based library tended to recognize the target molecules with high specificity, probably due to the native-like stable structure of vTAJ13. Our studies provide an example of the potential of de novo protein scaffolds, which are composed of a simplified amino acid set, to recognize a variety of target compounds.

  11. In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

    PubMed

    Buchanan, Kyle D; Torguson, Rebecca; Rogers, Toby; Xu, Linzhi; Gai, Jiaxiang; Ben-Dor, Itsik; Suddath, William O; Satler, Lowell F; Waksman, Ron

    2018-03-13

    Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p <0.001) and less often with myocardial infarction (6% vs 14%, p <0.001). One-year composite major adverse cardiovascular event, defined as death, Q-wave myocardial infarction, and target vessel revascularization, was 10% in the de novo group and 17% in the ISR group (hazard ratio 1.98, 95% confidential interval 1.58 to 2.46, p <0.001). After adjusting for myocardial infarction presentation, hazard ratio of major adverse cardiovascular events was still higher for the ISR group at 1 year (2.03, 95% confidential interval 1.62 to 2.55, p <0.001). ISR of DES remains a therapeutic challenge and leads to complex presentation and worse outcomes compared with matched de novo patients. These data show that DES-ISR demands better appreciation and prevention with more precise stent technique and should motivate the continued development of fully bioresorbable scaffolds. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

    PubMed

    Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

    2017-09-15

    The thyroid gland secretes primarily tetraiodothyronine (T 4 ), and some triiodothyronine (T 3 ). Under normal physiological circumstances, only one-fifth of circulating T 3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T 3 toxicosis. Thyroidal T 4 production results from iodination of thyroglobulin (TG) at residues Tyr 5 and Tyr 130 , whereas thyroidal T 3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T 3 is formed de novo independently of deiodination from T 4 We found that upon iodination in vitro , de novo T 3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T 3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T 3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T 3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T 3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T 3 formation, contributing to the relative T 3 toxicosis of Graves' disease.

  13. Automated de novo phasing and model building of coiled-coil proteins.

    PubMed

    Rämisch, Sebastian; Lizatović, Robert; André, Ingemar

    2015-03-01

    Models generated by de novo structure prediction can be very useful starting points for molecular replacement for systems where suitable structural homologues cannot be readily identified. Protein-protein complexes and de novo-designed proteins are examples of systems that can be challenging to phase. In this study, the potential of de novo models of protein complexes for use as starting points for molecular replacement is investigated. The approach is demonstrated using homomeric coiled-coil proteins, which are excellent model systems for oligomeric systems. Despite the stereotypical fold of coiled coils, initial phase estimation can be difficult and many structures have to be solved with experimental phasing. A method was developed for automatic structure determination of homomeric coiled coils from X-ray diffraction data. In a benchmark set of 24 coiled coils, ranging from dimers to pentamers with resolutions down to 2.5 Å, 22 systems were automatically solved, 11 of which had previously been solved by experimental phasing. The generated models contained 71-103% of the residues present in the deposited structures, had the correct sequence and had free R values that deviated on average by 0.01 from those of the respective reference structures. The electron-density maps were of sufficient quality that only minor manual editing was necessary to produce final structures. The method, named CCsolve, combines methods for de novo structure prediction, initial phase estimation and automated model building into one pipeline. CCsolve is robust against errors in the initial models and can readily be modified to make use of alternative crystallographic software. The results demonstrate the feasibility of de novo phasing of protein-protein complexes, an approach that could also be employed for other small systems beyond coiled coils.

  14. Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

    PubMed

    Chen, Yi-Chan; Cheng, Chih-Hsien; Wang, Yu-Chao; Wu, Ting-Jun; Chou, Hong-Shiue; Chan, Kun-Ming; Lee, Wei-Chen; Lee, Chen-Fang; Soong, Ruey Shyang

    2016-09-01

    Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population.From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports.Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population.Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

  15. Incidence, predictors, and procedural results of upgrade to resynchronization therapy: the RAFT upgrade substudy.

    PubMed

    Essebag, Vidal; Joza, Jacqueline; Birnie, David H; Sapp, John L; Sterns, Laurence D; Philippon, Francois; Yee, Raymond; Crystal, Eugene; Kus, Teresa; Rinne, Claus; Healey, Jeffrey S; Sami, Magdi; Thibault, Bernard; Exner, Derek V; Coutu, Benoit; Simpson, Chris S; Wulffhart, Zaev; Yetisir, Elizabeth; Wells, George; Tang, Anthony S L

    2015-02-01

    The resynchronization-defibrillation for ambulatory heart failure trial (RAFT) study demonstrated that adding cardiac resynchronization therapy (CRT) in selected patients requiring de novo implantable cardiac defibrillators (ICD) reduced mortality as compared with ICD therapy alone, despite an increase in procedure-related adverse events. Data are lacking regarding the management of patients with ICD therapy who develop an indication for CRT upgrade. Participating RAFT centers provided data regarding de novo CRT-D (CRT with ICD) implant, upgrade to CRT-D during RAFT (study upgrade), and upgrade within 6 months after presentation of study results (substudy). Substudy centers enrolled 1346 (74.9%) patients in RAFT, including 644 de novo, 80 study upgrade, and 60 substudy CRT attempts. The success rate (initial plus repeat attempts) was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (P=0.402). Acute complications occurred among 26.2% of de novo versus 18.8% of study upgrade and 3.4% of substudy CRT implantation attempts (P<0.001). The most common complication was left ventricular lead dislodgement. The principal reasons for not yet attempting upgrade in the substudy were patient preference (31.9%), New York Heart Association Class I (17.0%), and a QRS<150 ms (13.1%). Among a broad group of implant physicians, CRT upgrades were performed in patients with an ICD in situ with no difference in implant success rate and a reduced acute complication rate as compared with a de novo CRT implant. Decisions to upgrade were influenced by predictors of benefit in subgroup analyses of the RAFT study and other trials. © 2014 American Heart Association, Inc.

  16. Effect of plasminogen activator inhibitor-1 on adipogenesis in vivo.

    PubMed

    Scroyen, Ilse; Jacobs, Frank; Cosemans, Leen; De Geest, Bart; Lijnen, H Roger

    2009-02-01

    To study the functional role of plasminogen activator inhibitor-1 (PAI-1) in obesity, the effect of its overexpression on de novo adipogenesis was evaluated in murine models in vivo. Therefore, 3T3-F442A preadipocytes expressing murine PAI-1 (mPAI-1) or control cells were injected in the back of male NUDE mice, which were fed a high-fat diet (HFD) for four weeks. De novo fat pads that formed from the PAI-1 expressing cells were larger (21 +/- 2.4 mg vs. 14 +/- 1.4 mg; p = 0.017) and showed a higher adipocyte density (373 +/- 28 mm(-2) vs. 301 +/- 12 mm(-2); p = 0.03) as compared to those formed from control cells. In a second model, male NUDE mice were injected in the tail vein with an adenoviral construct expressing mPAI-1 or with the empty vector, and three days later with 3T3-F442A cells. After four weeks of HFD, total body weight and de novo fat pad weight were comparable for both groups. Mild adipocyte hypotrophy was observed in the de novo fat pads of the PAI-1 overexpressing mice (1180 +/- 33 microm(2) vs. 1285 +/- 32 microm(2); p = 0.024), whereas the blood vessel size was significantly smaller than in controls (30 +/- 1.8 microm(2) vs. 63 +/- 3.6 microm(2); p < 0.0001). Thus, the effect of local or systemic PAI-1 (over)expression on adipocyte or blood vessel size and density of de novo formed fat pads appears to be different, and concentration-dependent. Whereas local expression resulted in larger fat pads, systemic overexpression had no effect on de novo adipogenesis, although angiogenesis appeared to be impaired.

  17. Prenatally diagnosed de novo complex chromosome rearrangements: Two new cases and review of the literature

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

    Ruiz, C.; Grubs, R.E.; Jewett, T.

    1994-09-01

    Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical andmore » developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.« less

  18. Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

    PubMed

    Luscan, A; Just, P A; Briand, A; Burin des Roziers, C; Goussard, P; Nitschké, P; Vidaud, M; Avril, M F; Terris, B; Pasmant, E

    2015-04-01

    Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. De novo transciptome assembly in polyploid species

    USDA-ARS?s Scientific Manuscript database

    In the absence of a reference genome, the ultimate goal of a de novo transcriptome assembly is to accurately and comprehensively reconstruct the set of messenger RNA transcripts represented in the sample. Non-reference assembly of the transcriptome of polyploid species poses a particular challenge b...

  20. 75 FR 2544 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... engage de novo through its subsidiary, One World Asset Management, Inc., Dallas, Texas, in lending... Regulation Y (12 CFR Part 225) to engage de novo, or to acquire or control voting securities or assets of a...

  1. The De Novo Design of Protein-Protein Interfaces

    DTIC Science & Technology

    it was our intention to add to this body by engineering de novo (from scratch) protein/protein complexes. Using this inverse approach we have furthered...key physical features needed to drive specific protein/protein interactions. It is considered inverse because, instead of studying natural complexes

  2. Perception of local inhabitants regarding the socioeconomic impact of tourism focused on provisioning wild dolphins in Novo Airão, Central Amazon, Brazil.

    PubMed

    Alves, Luiz C P S; Zappes, Camilah A; Oliveira, Rafael G; Andriolo, Artur; Azevedo, Alexandre de F

    2013-01-01

    Botos (Inia geoffrensis) are currently provisioned for use in tourist attractions in five sites in the Brazilian Amazon. Despite the known negative effects associated with human-wild dolphin interactions, this activity has been regulated and licensed in the Anavilhanas National Park in Novo Airão, Amazonas State, Brazil. We present an updated evaluation of the perception of the local community concerning the possible socioeconomic impacts of this tourism in Novo Airão. In April 2011, 45 interviews were conducted with inhabitants. A small segment of Novo Airão perceives currently itself as being economically dependent on the botos feeding tourism. Despite that, the economic benefits of this controversial activity apparently are not shared among most inhabitants, and botos feeding tourism is perceived as generating diverse negative effects. We conclude that if the activity was banned or modified into a less impacting tourist activity, this action would probably not majorly affect the lives of the general population.

  3. Expression differences of programmed death ligand 1 in de-novo and recurrent glioblastoma multiforme

    PubMed Central

    Heynckes, Sabrina; Gaebelein, Annette; Haaker, Gerrit; Grauvogel, Jürgen; Franco, Pamela; Mader, Irina; Carro, Maria Stella; Prinz, Marco; Delev, Daniel; Schnell, Oliver; Heiland, Dieter Henrik

    2017-01-01

    The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits. We show that PD-L1 expression was reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide (TMZ) chemotherapy showed a significantly reduced level of PD-L1 expression in the recurrence stage compared to the corresponding de-novo tumour. Our findings may provide an explanation for potentially lower response to immunotherapy in the recurrent stage due to the reduced expression of the therapeutic target PD-L1. PMID:29088776

  4. [Use of "NovoSeven" (rFVIIa) hemostatic in patients operated with extracorporeal blood circulation].

    PubMed

    Dement'eva, I I; Sandrikov, V A; Charnaia, M A; Morozov, Iu A; Trekova, N A; Eremenko, A A

    2004-01-01

    The "NovoSeven" drug was used in 25 patients (male - 18, female - 7) operated on the heart and main vessels including with artificial extracorporeal circulation (AEC). Patients did not have any clinically significant impairment in blood circulation before surgery. Perioperatively, all of them and, immediately after surgery, 4 them had uncontrollable hemorrhages at 10-25 ml/min in spite of extensive hemostatic therapy, including freshly frozen plasma, cryoprecipitate, thromboconcentrate, trasilol and ?-amine acid. Yet in 30 min after "NovoSeven" administration, hemorrhages seized virtually in all patients irrespective of a surgical intervention. It normalized the hemostasis by it differential action on an impairment depending on an activated or suppressed coagulation. Thus, the conclusion is that the "NovoSeven" (rFVIIa) is an effective hemostatic ensuring the correction of massive intra- and postoperative blood losses in cardiosurgery patients. The drug cuts the need in using the donor-blood components, thus, diminishing the risk of multi organ failure that can develop immediately after surgery.

  5. Integrating genome assemblies with MAIA

    PubMed Central

    Nijkamp, Jurgen; Winterbach, Wynand; van den Broek, Marcel; Daran, Jean-Marc; Reinders, Marcel; de Ridder, Dick

    2010-01-01

    Motivation: De novo assembly of a eukaryotic genome with next-generation sequencing data is still a challenging task. Over the past few years several assemblers have been developed, often suitable for one specific type of sequencing data. The number of known genomes is expanding rapidly, therefore it becomes possible to use multiple reference genomes for assembly projects. We introduce an assembly integrator that makes use of all available data, i.e. multiple de novo assemblies and mappings against multiple related genomes, by optimizing a weighted combination of criteria. Results: The developed algorithm was applied on the de novo sequencing of the Saccharomyces cerevisiae CEN.PK 113-7D strain. Using Solexa and 454 read data, two de novo and three comparative assemblies were constructed and subsequently integrated, yielding 29 contigs, covering more than 12 Mbp; a drastic improvement compared with the single assemblies. Availability: MAIA is available as a Matlab package and can be downloaded from http://bioinformatics.tudelft.nl Contact: j.f.nijkamp@tudelft.nl PMID:20823304

  6. Identification of de novo mutations of Duchénnè/Becker muscular dystrophies in southern Spain.

    PubMed

    Garcia, Susana; de Haro, Tomás; Zafra-Ceres, Mercedes; Poyatos, Antonio; Gomez-Capilla, Jose A; Gomez-Llorente, Carolina

    2014-01-01

    Duchénnè/Becker muscular dystrophies (DMD/BMD) are X-linked diseases, which are caused by a de novo gene mutation in one-third of affected males. The study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain) and to establish the percentage of affected males in whom a de novo gene mutation was responsible. Multiplex ligation-dependent probe amplification (MLPA) technology was applied to determine the incidence of DMD/BMD in 84 males with suspicion of the disease and 106 female relatives. Dystrophin gene exon deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son pairs studied. MLPA technology is adequate for the molecular diagnosis of DMD/BMD and establishes whether the mother carries the molecular alteration responsible for the disease, a highly relevant issue for genetic counseling.

  7. Effects of Asterias amurensis-derived Sphingoid Bases on the de novo Ceramide Synthesis in Cultured Normal Human Epidermal Keratinocytes.

    PubMed

    Mikami, Daisuke; Sakai, Shota; Sasaki, Shigefumi; Igarashi, Yasuyuki

    2016-08-01

    Asterias amurensis starfish provide several bioactive species in addition to being fishery waste. Glucosyl ceramides (GlcCers) were extracted from the viscera of these starfish and were isolated by silica gel column chromatography. Degraded GlcCers generated A. amurensis sphingoid bases (ASBs) that mainly consisted of the triene-type bases d18:3 and 9-methyl-d18:3. The effect of these bases on ceramide synthesis and content were analyzed using normal human epidermal keratinocytes (NHEKs). The bases significantly enhanced the de novo ceramide synthesis and gene expression in NHEKs for proteins, such as serine-palmitoyltransferase and ceramide synthase. Total ceramide, GlcCer, and sphingomyelin contents increased dramatically upon ASB treatment. In particular, GlcCer bearing very-long-chain fatty acids (≥C28) exhibited a significant content increase. These ASB-induced enhancements on de novo ceramide synthesis were only observed in undifferentiated NHEKs. This stimulation of the de novo sphingolipid synthesis may improve skin barrier functions.

  8. De novo head and neck cancer arising in solid organ transplantation recipients: The Asan Medical Center experience.

    PubMed

    Park, Marn Joon; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Lee, Yoon Se

    2018-08-01

    De novo cancers of head and neck area in solid organ transplantation recipients show standardized incidence ratio (SIR) of 3.8. Immunosuppression following transplantation is suggested to play as a crucial factor in pathogenesis of secondary malignancy. Prognosis of head and neck cancer arising in solid organ transplantation recipients is proven to have poor prognosis. The incidence, risk, prognosis, and survival of de novo malignancy of head and neck area in solid organ transplantation recipients in single-tertiary medical center followed up for 20 years. A retrospective medical record review of the patients who received solid organ transplantation in Asan Medical Center from 1997 to 2016 was conducted. Patients confirmed as de novo malignancy in the head and neck area after organ transplantation were included, and presented as in the case-series format. Patients with previous history of head and neck malignancy, irradiation history of head and neck area, cutaneous malignant lesion, hematopoietic malignant lesion, malignancy of thyroid and parathyroid gland and metastatic lesions newly developed in head and neck area were excluded. The incidence of head and neck malignancy in South Korea were reviewed from the National Cancer Information Center of South Korea. For the statistical analysis, standardized incidence ratio (SIR) was obtained with 95% confidence interval. Solid organ transplantation recipients show 20 times higher incidence of de novo cancer of head and neck area compared to general population. Of 13 de novo head and neck malignancy arising after solid organ transplantation, 2 (15.4%) patients were unable to withstand definitive management due to poor general condition. 2 (15.4%) patients had loco-regional recurrence, 1 (7.7%) patient with distant metastasis, and 3 (23.1%) patients died of cancer progression. Immunosuppression following solid organ transplantation gives a twenty-fold increased risk for the development of de novo head and neck cancer. A more precise and frequent checkup on head and area should be planned, suggesting a multi-disciplinary approach in combination with organ transplantation team. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Airline Maintenance Manpower Optimization from the De Novo Perspective

    NASA Astrophysics Data System (ADS)

    Liou, James J. H.; Tzeng, Gwo-Hshiung

    Human resource management (HRM) is an important issue for today’s competitive airline marketing. In this paper, we discuss a multi-objective model designed from the De Novo perspective to help airlines optimize their maintenance manpower portfolio. The effectiveness of the model and solution algorithm is demonstrated in an empirical study of the optimization of the human resources needed for airline line maintenance. Both De Novo and traditional multiple objective programming (MOP) methods are analyzed. A comparison of the results with those of traditional MOP indicates that the proposed model and solution algorithm does provide better performance and an improved human resource portfolio.

  10. Progress toward a low budget reference grade genome assembly

    USDA-ARS?s Scientific Manuscript database

    Reference quality de novo genome assemblies were once solely the domain of large, well-funded genome projects. While next-generation short read technology removed some of the cost barriers, accurate chromosome-scale assembly remains a real challenge. Here we present efforts to de novo assemble the...

  11. 78 FR 36765 - Combined Notice of Filings #2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric corporate filings: Docket Numbers: EC13-117-000. Applicants: Novo BioPower LLC. Description: Section 203 Application of Novo BioPower LLC under EC13-117...

  12. Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors.

    PubMed

    Mills, Melissa B; Hudgins, Louanne; Balise, Raymond R; Abramson, David H; Kleinerman, Ruth A

    2012-07-01

    Autosomal dominant conditions are known to be associated with advanced paternal age, and it has been suggested that retinoblastoma (Rb) also exhibits a paternal age effect due to the paternal origin of most new germline RB1 mutations. To further our understanding of the association of parental age and risk of de novo germline RB1 mutations, we evaluated the effect of parental age in a cohort of Rb survivors in the United States. A cohort of 262 Rb patients was retrospectively identified at one institution, and telephone interviews were conducted with parents of 160 survivors (65.3%). We classified Rb survivors into three groups: those with unilateral Rb were classified as sporadic if they had no or unknown family history of Rb, those with bilateral Rb were classified as having a de novo germline mutation if they had no or unknown family history of Rb, and those with unilateral or bilateral Rb, who had a family history of Rb, were classified as familial. We built two sets of nested logistic regression models to detect an increased odds of the de novo germline mutation classification related to older parental age compared to sporadic and familial Rb classifications. The modeling strategy evaluated effects of continuous increasing maternal and paternal age and 5-year age increases adjusted for the age of the other parent. Mean maternal ages for survivors classified as having de novo germline mutations and sporadic Rb were similar (28.3 and 28.5, respectively) as were mean paternal ages (31.9 and 31.2, respectively), and all were significantly higher than the weighted general US population means. In contrast, maternal and paternal ages for familial Rb did not differ significantly from the weighted US general population means. Although we noted no significant differences between mean maternal and paternal ages between each of the three Rb classification groups, we found increased odds of a survivor being in the de novo germline mutation group for each 5-year increase in paternal age, but these findings were not statistically significant (de novo vs. sporadic ORs 30-34 = 1.7 [0.7-4], ≥ 35 = 1.3 [0.5-3.3]; de novo vs. familial ORs 30-34 = 2.8 [1.0-8.4], ≥ 35 = 1.6 [0.6-4.6]). Our study suggests a weak paternal age effect for Rb resulting from de novo germline mutations consistent with the paternal origin of most of these mutations.

  13. Regulation of Purine Metabolism in Intact Leaves of Coffea arabica.

    PubMed

    Nazario, G. M.; Lovatt, C. J.

    1993-12-01

    The capacity of Coffea arabica leaves (5- x 5-mm pieces) to synthesize de novo and catabolize purine nucleotides to provide precursors for caffeine (1,3,7-trimethylxanthine) was investigated. Consistent with de novo synthesis, glycine, bicarbonate, and formate were incorporated into the purine ring of inosine 5[prime]-monophosphate (IMP) and adenine nucleotides ([sigma]Ade); azaserine, a known inhibitor of purine de novo synthesis, inhibited incorporation. Activity of the de novo pathway in C. arabica per g fresh weight of leaf tissue during a 3-h incubation period was 8 [plus or minus] 4 nmol of formate incorporated into IMP, 61 [plus or minus] 7 nmol into [sigma]Ade, and 150 nmol into caffeine (the latter during a 7-h incubation). Coffee leaves exhibited classical purine catabolism. Radiolabeled formate, inosine, adenosine, and adenine were incorporated into hypoxanthine and xanthine, which were catabolized to allantoin and urea. Urease activity was demonstrated. Per g fresh weight, coffee leaf squares incorporated 90 [plus or minus] 22 nmol of xanthine into caffeine in 7 h but degraded 102 [plus or minus] 1 nmol of xanthine to allantoin in 3 h. Feedback control of de novo purine biosynthesis was contrasted in C. arabica and Cucurbita pepo, a species that does not synthesize purine alkaloids. End-product inhibition was demonstrated to occur in both species but at different enzyme reactions.

  14. Lessons Learned From a Case of Gastric Cancer After Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Yang, Kun; Zhu, Hong; Chen, Chong-Cheng; Wen, Tian-Fu; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Guo, Dong-Jiao; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Abstract Nowadays, de novo malignancies have become an important cause of death after transplantation. According to the accumulation of cases with liver transplantation, the incidence of de novo gastric cancer is anticipated to increase among liver transplant recipients in the near future, especially in some East Asian countries where both liver diseases requiring liver transplantation and gastric cancer are major burdens. Unfortunately, there is limited information regarding the relationship between de novo gastric cancer and liver transplantation. Herein, we report a case of stage IIIc gastric cancer after liver transplantation for hepatocellular carcinoma, who was successfully treated by radical distal gastrectomy with D2 lymphadenectomy but died 15 months later due to tumor progression. Furthermore, we extract some lessons to learn from the case and review the literatures. The incidence of de novo gastric cancer following liver transplantations is increasing and higher than the general population. Doctors should be vigilant in early detection and control the risk factors causing de novo gastric cancer after liver transplantation. Curative gastrectomy with D2 lymphadenectomy is still the mainstay of treatment for such patients. Preoperative assessments, strict postoperative monitoring, and managements are mandatory. Limited chemotherapy could be given to the patients with high risk of recurrence. Close surveillance, early detection, and treatment of posttransplant cancers are extremely important and essential to improve the survival. PMID:26886605

  15. Drug-coated balloon angioplasty for de novo small vessel disease including chronic total occlusion and bifurcation in real-world clinical practice.

    PubMed

    Onishi, Takayuki; Onishi, Yuko; Kobayashi, Isshi; Umezawa, Shigeo; Niwa, Akihiro

    2018-06-18

    The aim of this study is to validate the efficacy of drug-coated balloons (DCBs) for real-world de novo small vessel diseases including chronic total occlusion and bifurcation. DCB angioplasty has been reported to be effective in the treatment of de novo small vessel disease. However, the number of reports that have focused on complex lesions is limited. This observational study comprised consecutive patients who underwent DCB angioplasty for de novo small vessel disease with a reference diameter of less than 2.5 mm by visual estimation. Outcome parameters included late lumen loss, restenosis rate, and major adverse cardiac events, such as cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). Fifty-two patients underwent DCB angioplasty for 59 lesions with a reference vessel diameter of 1.93 ± 0.63 mm. Thirty-eight of the lesions (69%) were classified as type B2/C, including chronic total occlusions (20%) and bifurcations (33%). At the 8-month follow-up, late lumen loss was - 0.01 ± 0.44 mm with a restenosis rate of 20%. No cardiac deaths or myocardial infarctions were reported and only 5 (9%) angiographically driven TLRs were reported. DCB angioplasty offered an acceptable 8-month lumen patency and a stable clinical outcome for real-world complex de novo coronary diseases.

  16. De novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth.

    PubMed

    Schäfgen, Johanna; Cremer, Kirsten; Becker, Jessica; Wieland, Thomas; Zink, Alexander M; Kim, Sarah; Windheuser, Isabelle C; Kreiß, Martina; Aretz, Stefan; Strom, Tim M; Wieczorek, Dagmar; Engels, Hartmut

    2016-12-01

    Recently, germline variants of the transcriptional co-regulator gene TCF20 have been implicated in the aetiology of autism spectrum disorders (ASD). However, the knowledge about the associated clinical picture remains fragmentary. In this study, two individuals with de novo TCF20 sequence variants were identified in a cohort of 313 individuals with intellectual disability of unknown aetiology, which was analysed by whole exome sequencing using a child-parent trio design. Both detected variants - one nonsense and one frameshift variant - were truncating. A comprehensive clinical characterisation of the patients yielded mild intellectual disability, postnatal tall stature and macrocephaly, obesity and muscular hypotonia as common clinical signs while ASD was only present in one proband. The present report begins to establish the clinical picture of individuals with de novo nonsense and frameshift variants of TCF20 which includes features such as proportionate overgrowth and muscular hypotonia. Furthermore, intellectual disability/developmental delay seems to be fully penetrant amongst known individuals with de novo nonsense and frameshift variants of TCF20, whereas ASD is shown to be incompletely penetrant. The transcriptional co-regulator gene TCF20 is hereby added to the growing number of genes implicated in the aetiology of both ASD and intellectual disability. Furthermore, such de novo variants of TCF20 may represent a novel differential diagnosis in the overgrowth syndrome spectrum.

  17. Inhibition of selenocysteine tRNA[Ser]Sec aminoacylation provides evidence that aminoacylation is required for regulatory methylation of this tRNA

    PubMed Central

    Kim, Jin Young; Carlson, Bradley A.; Xu, Xue-Ming; Zeng, Yu; Chen, Shawn; Gladyshev, Vadim N.; Lee, Byeong Jae; Hatfield, Dolph L.

    2011-01-01

    There are two isoforms of selenocysteine (Sec) tRNA[Ser]Sec that differ by a single methyl group, Um34. The non-Um34 isoform supports the synthesis of a subclass of selenoproteins, designated housekeeping, while the Um34 isoform supports the expression of another subclass, designated stress-related selenoproteins. Herein, we investigated the relationship between tRNA[Ser]Sec aminoacylation and Um34 synthesis which is the last step in the maturation of this tRNA. Mutation of the discriminator base at position 73 in tRNA[Ser]Sec dramatically reduced aminoacylation with serine, as did an inhibitor of seryl-tRNA synthetase, SB-217452. Although both the mutation and the inhibitor prevented Um34 synthesis, neither precluded the synthesis of any other of the known base modifications on tRNA[Ser]Sec following microinjection and incubation of the mutant tRNA[Ser]Sec transcript, or the wild type transcript along with inhibitor, in Xenopus oocytes. The data demonstrate that Sec tRNA[Ser]Sec must be aminoacylated for Um34 addition. The fact that selenium is required for Um34 methylation suggests that Sec must be attached to its tRNA for Um34 methylation. This would explain why selenium is essential for the function of Um34 methylase and provides further insights into the hierarchy of selenoprotein expression. PMID:21624347

  18. Long-read sequencing and de novo assembly of a Chinese genome

    USDA-ARS?s Scientific Manuscript database

    Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arr...

  19. Glutamine supplementation, citrulline production, and de novo arginine synthesis: Is there a relation?

    USDA-ARS?s Scientific Manuscript database

    We would like to comment on the recent publications by Buijs et al. The authors hypothesized that a parenteral supplement of glutamine stimulates citrulline formation and enhances de novo arginine synthesis. To test this hypothesis, they conducted an experiment with stable isotopes in patients under...

  20. The glucose sensor ChREBP links de-novo lipogenesis to PPARgamma activity and adipocyte differentiation

    USDA-ARS?s Scientific Manuscript database

    Reduced de-novo lipogenesis DNL)in adipose tissue, often observed in obese individuals, is thought to contribute to insulin resistance. Besides trapping excess glucose and providing for triglycerides and energy storage, endogenously synthesized lipids can function as potent signaling molecules. Inde...

  1. De novo genome assembly of Cercospora beticola for microsatellite marker development and validation

    USDA-ARS?s Scientific Manuscript database

    Cercospora leaf spot caused by Cercospora beticola is a significant threat to the production of sugar and table beet worldwide. A de novo genome assembly of C. beticola was used to develop eight polymorphic and reproducible microsatellite markers for population genetic analyses. These markers were u...

  2. Thermodynamics of Anharmonic Systems: Uncoupled Mode Approximations for Molecules

    DOE PAGES

    Li, Yi-Pei; Bell, Alexis T.; Head-Gordon, Martin

    2016-05-26

    The partition functions, heat capacities, entropies, and enthalpies of selected molecules were calculated using uncoupled mode (UM) approximations, where the full-dimensional potential energy surface for internal motions was modeled as a sum of independent one-dimensional potentials for each mode. The computational cost of such approaches scales the same with molecular size as standard harmonic oscillator vibrational analysis using harmonic frequencies (HO hf). To compute thermodynamic properties, a computational protocol for obtaining the energy levels of each mode was established. The accuracy of the UM approximation depends strongly on how the one-dimensional potentials of each modes are defined. If the potentialsmore » are determined by the energy as a function of displacement along each normal mode (UM-N), the accuracies of the calculated thermodynamic properties are not significantly improved versus the HO hf model. Significant improvements can be achieved by constructing potentials for internal rotations and vibrations using the energy surfaces along the torsional coordinates and the remaining vibrational normal modes, respectively (UM-VT). For hydrogen peroxide and its isotopologs at 300 K, UM-VT captures more than 70% of the partition functions on average. By con trast, the HO hf model and UM-N can capture no more than 50%. For a selected test set of C2 to C8 linear and branched alkanes and species with different moieties, the enthalpies calculated using the HO hf model, UM-N, and UM-VT are all quite accurate comparing with reference values though the RMS errors of the HO model and UM-N are slightly higher than UM-VT. However, the accuracies in entropy calculations differ significantly between these three models. For the same test set, the RMS error of the standard entropies calculated by UM-VT is 2.18 cal mol -1 K -1 at 1000 K. By contrast, the RMS error obtained using the HO model and UM-N are 6.42 and 5.73 cal mol -1 K -1, respectively. For a test set composed of nine alkanes ranging from C5 to C8, the heat capacities calculated with the UM-VT model agree with the experimental values to within a RMS error of 0.78 cal mol -1 K -1 , which is less than one-third of the RMS error of the HO hf (2.69 cal mol -1 K -1) and UM-N (2.41 cal mol -1 K -1) models.« less

  3. STS-40 Exp. No. 192 urine monitoring system (UMS) on OV-102's middeck

    NASA Technical Reports Server (NTRS)

    1991-01-01

    STS-40 Experiment No. 192, Fluid-Electrolyte Regulation During Space Flight, urine monitoring system (UMS) is set up on the middeck of Columbia, Orbiter Vehicle (OV) 102, at the side hatch. The UMS is attached to OV-102's waste collection system (WCS). The urine specimen tray with sample tubes appears to the right of the UMS equipment.

  4. In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status.

    PubMed

    Reid, Paul; Wilson, Puthenparampil; Li, Yanrui; Marcu, Loredana G; Staudacher, Alexander H; Brown, Michael P; Bezak, Eva

    2017-01-01

    Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome. Baseline and post-irradiation changes in CSC proportions were investigated by flow cytometry in a HPV-negative (UM-SCC-1) and a HPV-positive (UM-SCC-47) HNSCC cell line, using fluorescent staining with CD44/ALDH markers. CSC proportions in both irradiated and unirradiated cultures were compared for the two cell lines at various times post-irradiation. To assess repopulation of CSCs, untreated cultures were depleted of CD44+/ALDH+ cells and re-cultured for 3 weeks before flow cytometry analysis. CSC proportions in untreated cell lines were 0.57% (UM-SCC-1) and 2.87% (UM-SCC-47). Untreated cell lines depleted of CD44+/ALDH+ repopulated this phenotype to a mean of 0.15% (UM-SCC-1) and 6.76% (UM-SCC-47). All UM-SCC-47 generations showed elevated CSC proportions after irradiation, with the most significant increase at 2 days post-irradiation. The highest elevation in UM-SCC-1 CSCs was observed at 1 day post-irradiation in the 2nd generation and at 3 days after irradiation in the 3rd generation. When measured after 10 days, only the 3rd generation of UM-SCC-1 showed elevated CSCs. CSC proportions in both cell lines were elevated after exposure and varied with time post irradiation. UM-SCC-47 displayed significant plasticity in repopulating the CSC phenotype in depleted cultures, which was not seen in UM-SCC-1.

  5. De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

    PubMed

    Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

    2016-01-01

    We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

  6. Study of factors affecting growth and cold acclimation of Vitis callus cultures

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

    Deng, L.

    1987-01-01

    In vitro grape tissue culture initiation, growth, and cold acclimation were studied. Factors involved were genotypes, media, plant growth regulators, age, light, temperature, antioxidant, clearing and adsorbing agents, sucrose level, osmotic potential, ABA, chilling and freezing treatments. Murashige and Skoog (MS) medium containing 1 ..mu..M 2,4-d + 0.1 uM Ba, MS containing 1 uM 2,4-D, and woody plant medium containing 1 uM 2,4-D + 0.1 uM BA produced abundant callus tissue for most grape genotypes; either WPM or MS containing 1 uM BA stimulated shoot growth in all the 12 genotypes tested. Adding 1 uM abscisic acid (ABA) to themore » B5 medium with 1 uM 2,4-D and 0.5 uM BA enhanced growth and quality of Chancellor callus. /sup 3/H-ABA was taken up actively by callus tissue at 12 days after subculture, but by 20 d this effect disappeared. When /sup 14/C-sucrose was added to the medium. /sup 14/C level of cells reached a plateau after 48 h; this plateau was higher if ABA was also present in the medium. Cells on media containing ABA were larger in size, lighter in color, and more loosely connected.« less

  7. GPU-Accelerated Optical Coherence Tomography Signal Processing and Visualization

    NASA Astrophysics Data System (ADS)

    Darbrazi, Seyed Hamid Hosseiny

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  8. Albumin and fibronectin adsorption and osteoblast adhesion on titanium oxides

    NASA Astrophysics Data System (ADS)

    Freitas, Susana Maria Ribeiro e. Sousa Mendes de

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  9. Birefringence and Bragg grating control in femtosecond laser written optical circuits

    NASA Astrophysics Data System (ADS)

    Fernandes, Luis A.

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  10. Single Point Incremental Forming and Multi-Stage Incremental Forming on Aluminium Alloy 1050

    NASA Astrophysics Data System (ADS)

    Suriyaprakan, Premika

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  11. Magnetism at the nanoscale: Nanoparticles, nanowires, nanotubes and their ordered arrays

    NASA Astrophysics Data System (ADS)

    Proenca, Mariana Jesus Paiva

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  12. Improving the characteristics of foundry alloys AlSiCuMg during manufacturing

    NASA Astrophysics Data System (ADS)

    Fragoso, Bruno Filipe Marques

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  13. Seismic assessment of reinforced concrete frame structures with a new flexibility based element

    NASA Astrophysics Data System (ADS)

    Arede, Antonio Jose Coelho Dias

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  14. Viscoelastic nanocapsules under flow in microdevices

    NASA Astrophysics Data System (ADS)

    Cordeiro, Ana Lucinda Teixeira

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  15. Stellar activity in high-precision photometric and spectroscopic transit observations

    NASA Astrophysics Data System (ADS)

    Oshagh, Mahmoudreza

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  16. Starch and polyethylene based bone-analogue composite biomaterials

    NASA Astrophysics Data System (ADS)

    Reis, Rui Luis Goncalves dos

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  17. Clinopyroxene based glasses and glass-ceramics for functional applications

    NASA Astrophysics Data System (ADS)

    Goel, Ashutosh

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  18. Highly efficient de novo mutant identification in a sorghum bicolor tilling population using the ComSeq approach

    USDA-ARS?s Scientific Manuscript database

    Screening large populations for carriers of known or de novo rare SNPs is required both in Targeting induced local lesions IN genomes (TILLING) experiments in plants and analogously in screening human populations. We formerly suggested an approach that combines the celebrated mathematical field of c...

  19. MetaVelvet: An Extension of Velvet Assembler to de novo Metagenome Assembly from Short Sequence Reads (Metagenomics Informatics Challenges Workshop: 10K Genomes at a Time)

    ScienceCinema

    Sakakibara, Yasumbumi

    2018-02-13

    Keio University's Yasumbumi Sakakibara on "MetaVelvet: An Extension of Velvet Assembler to de novo Metagenome Assembly from Short Sequence Reads" at the Metagenomics Informatics Challenges Workshop held at the DOE JGI on October 12-13, 2011.

  20. New Approaches and Technologies to Sequence de novo Plant reference Genomes (2013 DOE JGI Genomics of Energy and Environment 8th Annual User Meeting)

    ScienceCinema

    Schmutz, Jeremy

    2018-02-01

    Jeremy Schmutz of the HudsonAlpha Institute for Biotechnology on New approaches and technologies to sequence de novo plant reference genomes at the 8th Annual Genomics of Energy Environment Meeting on March 27, 2013 in Walnut Creek, CA.

  1. MetaVelvet: An Extension of Velvet Assembler to de novo Metagenome Assembly from Short Sequence Reads (Metagenomics Informatics Challenges Workshop: 10K Genomes at a Time)

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

    Sakakibara, Yasumbumi

    2011-10-13

    Keio University's Yasumbumi Sakakibara on "MetaVelvet: An Extension of Velvet Assembler to de novo Metagenome Assembly from Short Sequence Reads" at the Metagenomics Informatics Challenges Workshop held at the DOE JGI on October 12-13, 2011.

  2. De novo synthesis of milk triglycerides in humans

    USDA-ARS?s Scientific Manuscript database

    Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk tha...

  3. Genome-wide analyses of the Dutch elm disease fungi

    Treesearch

    Louis Bernier

    2017-01-01

    The Ascomycete fungi Ophiostoma ulmi and O. novo-ulmi are the pathogens respectively responsible for the two successive pandemics of Dutch elm disease (DED) since the early 1900s. The advent of the highly fit and virulent O. novo-ulmi was a landmark event in the evolution of DED during the last 100 years....

  4. New Approaches and Technologies to Sequence de novo Plant reference Genomes (2013 DOE JGI Genomics of Energy and Environment 8th Annual User Meeting)

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

    Schmutz, Jeremy

    2013-03-01

    Jeremy Schmutz of the HudsonAlpha Institute for Biotechnology on New approaches and technologies to sequence de novo plant reference genomes at the 8th Annual Genomics of Energy Environment Meeting on March 27, 2013 in Walnut Creek, CA.

  5. A Public Trial De Novo: Rethinking "Industrial Interests"

    ERIC Educational Resources Information Center

    Vedel, Jane Bjorn; Gad, Christopher

    2011-01-01

    This article addresses the concept of "industrial interests" and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a "public trial" where the grant and close(r)…

  6. Rate of de novo mutations and the importance of father's age to disease risk.

    PubMed

    Kong, Augustine; Frigge, Michael L; Masson, Gisli; Besenbacher, Soren; Sulem, Patrick; Magnusson, Gisli; Gudjonsson, Sigurjon A; Sigurdsson, Asgeir; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Wong, Wendy S W; Sigurdsson, Gunnar; Walters, G Bragi; Steinberg, Stacy; Helgason, Hannes; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Helgason, Agnar; Magnusson, Olafur Th; Thorsteinsdottir, Unnur; Stefansson, Kari

    2012-08-23

    Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20 × 10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism.

  7. De novo-based transcriptome profiling of male-sterile and fertile watermelon lines

    PubMed Central

    Seo, Minseok; Jang, Yoon Jeong; Sim, Tae Yong; Cho, Seoae; Han, Sang-Wook

    2017-01-01

    The whole-genome sequence of watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai), a valuable horticultural crop worldwide, was released in 2013. Here, we compared a de novo-based approach (DBA) to a reference-based approach (RBA) using RNA-seq data, to aid in efforts to improve the annotation of the watermelon reference genome and to obtain biological insight into male-sterility in watermelon. We applied these techniques to available data from two watermelon lines: the male-sterile line DAH3615-MS and the male-fertile line DAH3615. Using DBA, we newly annotated 855 watermelon transcripts, and found gene functional clusters predicted to be related to stimulus responses, nucleic acid binding, transmembrane transport, homeostasis, and Golgi/vesicles. Among the DBA-annotated transcripts, 138 de novo-exclusive differentially-expressed genes (DEDEGs) related to male sterility were detected. Out of 33 randomly selected newly annotated transcripts and DEDEGs, 32 were validated by RT-qPCR. This study demonstrates the usefulness and reliability of the de novo transcriptome assembly in watermelon, and provides new insights for researchers exploring transcriptional blueprints with regard to the male sterility. PMID:29095876

  8. Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling.

    PubMed

    Scarlatti, Francesca; Sala, Giusy; Somenzi, Giulia; Signorelli, Paola; Sacchi, Nicoletta; Ghidoni, Riccardo

    2003-12-01

    Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L-cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA-MB-231 by activating the de novo ceramide synthesis pathway.

  9. Repair after nephron ablation reveals limitations of neonatal neonephrogenesis

    PubMed Central

    Tögel, Florian; Freedman, Benjamin S.; Iatrino, Rossella; Grinstein, Mor; Bonventre, Joseph V.

    2017-01-01

    The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral nephrectomy during the neonatal period or after 1 week of age. There was no detectable compensatory de novo nephrogenesis, as determined by glomerular counting and lineage tracing. Contralateral nephrectomy resulted in additional adaptive healing, with little or no fibrosis, but did not also stimulate de novo nephrogenesis. In contrast, injury initiated at 1 week of age led to healing with fibrosis. Thus, despite the presence of progenitor cells and ongoing nephron maturation in the newborn mouse kidney, de novo nephrogenesis is not inducible by acute nephron reduction. This indicates that additional nephron progenitors cannot be recruited after birth despite partial renal ablation providing a reparative stimulus and suggests that nephron number in the mouse is predetermined at birth. PMID:28138555

  10. The long reads ahead: de novo genome assembly using the MinION

    PubMed Central

    de Lannoy, Carlos; de Ridder, Dick; Risse, Judith

    2017-01-01

    Nanopore technology provides a novel approach to DNA sequencing that yields long, label-free reads of constant quality. The first commercial implementation of this approach, the MinION, has shown promise in various sequencing applications. This review gives an up-to-date overview of the MinION's utility as a de novo sequencing device. It is argued that the MinION may allow for portable and affordable de novo sequencing of even complex genomes in the near future, despite the currently error-prone nature of its reads. Through continuous updates to the MinION hardware and the development of new assembly pipelines, both sequencing accuracy and assembly quality have already risen rapidly. However, this fast pace of development has also lead to a lack of overview of the expanding landscape of analysis tools, as performance evaluations are outdated quickly. As the MinION is approaching a state of maturity, its user community would benefit from a thorough comparative benchmarking effort of de novo assembly pipelines in the near future. An earlier version of this article can be found on  bioRxiv. PMID:29375809

  11. 3.3 Ga SHRIMP U-Pb zircon age of a felsic metavolcanic rock from the Mundo Novo greenstone belt in the São Francisco craton, Bahia (NE Brazil)

    NASA Astrophysics Data System (ADS)

    Peucat, J. J.; Mascarenhas, J. F.; Barbosa, J. S. F.; de Souza, S. L.; Marinho, M. M.; Fanning, C. M.; Leite, C. M. M.

    2002-07-01

    Felsic metavolcanics associated with supracrustal rocks provide U-Pb zircon and Sm-Nd TDM ages of approximately 3.3 Ga, which establish an Archean age of the Mundo Novo greenstone belt. A granodioritic gneiss from the Mairi complex, located on the eastern boundary of the Mundo Novo greenstone belt, exhibits a zircon evaporation minimum age of 3.04 Ga and a Nd model age of 3.2 Ga. These results constrain the occurrence of at least three major geological units in this area: the Archean Mundo Novo greenstone belt, the Archean Mairi gneisses, and the adjoining Paleoproterozoic (<2.1 Ga) Jacobina sedimentary basin. The Jacobina basin follows the same trend as the Archean structure, extending southward to the Contendas-Mirante belt, in which a similar Archean-Paleoproterozoic association appears. We postulate that during the Paleoproterozoic in the eastern margin of the Gavião block, these Archean greenstone belts constituted a zone of weakness along which a late-stage orogenic sedimentary basin developed.

  12. De Novo Peptide Sequencing: Deep Mining of High-Resolution Mass Spectrometry Data.

    PubMed

    Islam, Mohammad Tawhidul; Mohamedali, Abidali; Fernandes, Criselda Santan; Baker, Mark S; Ranganathan, Shoba

    2017-01-01

    High resolution mass spectrometry has revolutionized proteomics over the past decade, resulting in tremendous amounts of data in the form of mass spectra, being generated in a relatively short span of time. The mining of this spectral data for analysis and interpretation though has lagged behind such that potentially valuable data is being overlooked because it does not fit into the mold of traditional database searching methodologies. Although the analysis of spectra by de novo sequences removes such biases and has been available for a long period of time, its uptake has been slow or almost nonexistent within the scientific community. In this chapter, we propose a methodology to integrate de novo peptide sequencing using three commonly available software solutions in tandem, complemented by homology searching, and manual validation of spectra. This simplified method would allow greater use of de novo sequencing approaches and potentially greatly increase proteome coverage leading to the unearthing of valuable insights into protein biology, especially of organisms whose genomes have been recently sequenced or are poorly annotated.

  13. Combining De Novo Peptide Sequencing Algorithms, A Synergistic Approach to Boost Both Identifications and Confidence in Bottom-up Proteomics.

    PubMed

    Blank-Landeshammer, Bernhard; Kollipara, Laxmikanth; Biß, Karsten; Pfenninger, Markus; Malchow, Sebastian; Shuvaev, Konstantin; Zahedi, René P; Sickmann, Albert

    2017-09-01

    Complex mass spectrometry based proteomics data sets are mostly analyzed by protein database searches. While this approach performs considerably well for sequenced organisms, direct inference of peptide sequences from tandem mass spectra, i.e., de novo peptide sequencing, oftentimes is the only way to obtain information when protein databases are absent. However, available algorithms suffer from drawbacks such as lack of validation and often high rates of false positive hits (FP). Here we present a simple method of combining results from commonly available de novo peptide sequencing algorithms, which in conjunction with minor tweaks in data acquisition ensues lower empirical FDR compared to the analysis using single algorithms. Results were validated using state-of-the art database search algorithms as well specifically synthesized reference peptides. Thus, we could increase the number of PSMs meeting a stringent FDR of 5% more than 3-fold compared to the single best de novo sequencing algorithm alone, accounting for an average of 11 120 PSMs (combined) instead of 3476 PSMs (alone) in triplicate 2 h LC-MS runs of tryptic HeLa digestion.

  14. Generative Recurrent Networks for De Novo Drug Design.

    PubMed

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  15. Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

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

    Hoffman, J.M.; Standaert, M.L.; Nair, G.P.

    1991-04-02

    Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in ({sup 3}H)glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked themore » later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 {mu}M sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis.« less

  16. E-novo: an automated workflow for efficient structure-based lead optimization.

    PubMed

    Pearce, Bradley C; Langley, David R; Kang, Jia; Huang, Hongwei; Kulkarni, Amit

    2009-07-01

    An automated E-Novo protocol designed as a structure-based lead optimization tool was prepared through Pipeline Pilot with existing CHARMm components in Discovery Studio. A scaffold core having 3D binding coordinates of interest is generated from a ligand-bound protein structural model. Ligands of interest are generated from the scaffold using an R-group fragmentation/enumeration tool within E-Novo, with their cores aligned. The ligand side chains are conformationally sampled and are subjected to core-constrained protein docking, using a modified CHARMm-based CDOCKER method to generate top poses along with CDOCKER energies. In the final stage of E-Novo, a physics-based binding energy scoring function ranks the top ligand CDOCKER poses using a more accurate Molecular Mechanics-Generalized Born with Surface Area method. Correlation of the calculated ligand binding energies with experimental binding affinities were used to validate protocol performance. Inhibitors of Src tyrosine kinase, CDK2 kinase, beta-secretase, factor Xa, HIV protease, and thrombin were used to test the protocol using published ligand crystal structure data within reasonably defined binding sites. In-house Respiratory Syncytial Virus inhibitor data were used as a more challenging test set using a hand-built binding model. Least squares fits for all data sets suggested reasonable validation of the protocol within the context of observed ligand binding poses. The E-Novo protocol provides a convenient all-in-one structure-based design process for rapid assessment and scoring of lead optimization libraries.

  17. Stimulated nitric oxide production and arginine deficiency in children with cystic fibrosis with nutritional failure.

    PubMed

    Engelen, Mariëlle P K J; Com, Gulnur; Luiking, Yvette C; Deutz, Nicolaas E P

    2013-08-01

    To determine whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide (NO) production in pediatric patients with cystic fibrosis (CF) and nutritional failure. In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline (Cit), and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. Increased arginine clearance was found in patients with CF (P < .001), whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P < .001), de novo arginine synthesis, and protein breakdown and synthesis (P < .05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n = 7) had significantly higher NO production (P < .05), de novo arginine synthesis, Cit production (P < .001), and plasma Cit concentration (P < .05) and lower plasma arginine concentration (P < .05) than those without nutritional failure (n = 9). Nutritional failure in CF is associated with increased NO production. However, up-regulation of de novo arginine synthesis and Cit production was not sufficient to meet the increased arginine needs leading to arginine deficiency. Copyright © 2013 Mosby, Inc. All rights reserved.

  18. Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia.

    PubMed

    Zhao, Hongli; Zhao, Yanqiu; Zhang, Yingmei; Hou, Jinxiao; Yang, Huiyuan; Cao, Fenglin; Yang, Yiju; Hou, Wenyi; Sun, Jiayue; Jin, Bo; Fu, Jinyue; Li, Haitao; Wang, Ping; Ge, Fei; Zhou, Jin

    2018-03-01

    Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 10 9 /L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 10 9 /L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

  19. A combined de novo protein sequencing and cDNA library approach to the venomic analysis of Chinese spider Araneus ventricosus.

    PubMed

    Duan, Zhigui; Cao, Rui; Jiang, Liping; Liang, Songping

    2013-01-14

    In past years, spider venoms have attracted increasing attention due to their extraordinary chemical and pharmacological diversity. The recently popularized proteomic method highly improved our ability to analyze the proteins in the venom. However, the lack of information about isolated venom proteins sequences dramatically limits the ability to confidently identify venom proteins. In the present paper, the venom from Araneus ventricosus was analyzed using two complementary approaches: 2-DE/Shotgun-LC-MS/MS coupled to MASCOT search and 2-DE/Shotgun-LC-MS/MS coupled to manual de novo sequencing followed by local venom protein database (LVPD) search. The LVPD was constructed with toxin-like protein sequences obtained from the analysis of cDNA library from A. ventricosus venom glands. Our results indicate that a total of 130 toxin-like protein sequences were unambiguously identified by manual de novo sequencing coupled to LVPD search, accounting for 86.67% of all toxin-like proteins in LVPD. Thus manual de novo sequencing coupled to LVPD search was proved an extremely effective approach for the analysis of venom proteins. In addition, the approach displays impeccable advantage in validating mutant positions of isoforms from the same toxin-like family. Intriguingly, methyl esterifcation of glutamic acid was discovered for the first time in animal venom proteins by manual de novo sequencing. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  20. De novo immune complex deposition in kidney allografts: a series of 32 patients.

    PubMed

    Lloyd, Isaac E; Ahmed, Faris; Revelo, Monica P; Khalighi, Mazdak A

    2018-01-01

    Immune complex deposition in kidney allografts can include both recurrent and de novo processes. Recurrent glomerulonephritis is a well-recognized phenomenon and has been shown to be a common cause of allograft failure. De novo immune complex-mediated disease remains relatively poorly characterized, likely owing to the less frequent use of immunofluorescence and electron microscopy in the transplant setting. We performed a retrospective review of kidney allograft biopsies showing glomerular immune complex deposition. Cases with de novo deposits were identified and further organized into two groups depending on whether the immune complex deposition could be clinically and/or histologically classified. Thirty-two patients with de novo immune complex deposition were identified over a 7-year period. A broad range of immune complex-mediated injuries were observed, the majority (63%) of which could be readily classified either clinically or histologically. These included cases of membranous glomerulonephropathy, IgA nephropathy, infection-related glomerulonephritis and glomerulonephritis related to an underlying autoimmune process. A smaller subset of patients (37%) demonstrated immune complex deposition that was difficult to histologically or clinically classify. These patients typically showed mild mesangial immune complex deposition with co-dominant IgG and IgM staining by immunofluorescence microscopy. The presence of concurrent antibody-mediated rejection and donor-specific antibody positivity was significantly higher in the unclassifiable group. The significance of these deposits and their possible relationship to allograft rejection deserves further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Boehringer Mannheim award lecture 1995. La conference Boehringer Mannheim 1995. De novo design of alpha-helical proteins: basic research to medical applications.

    PubMed

    Hodges, R S

    1996-01-01

    The two-stranded alpha-helical coiled-coil is a universal dimerization domain used by nature in a diverse group of proteins. The simplicity of the coiled-coil structure makes it an ideal model system to use in understanding the fundamentals of protein folding and stability and in testing the principles of de novo design. The issues that must be addressed in the de novo design of coiled-coils for use in research and medical applications are (i) controlling parallel versus antiparallel orientation of the polypeptide chains, (ii) controlling the number of helical strands in the assembly (iii) maximizing stability of homodimers or heterodimers in the shortest possible chain length that may require the engineering of covalent constraints, and (iv) the ability to have selective heterodimerization without homodimerization, which requires a balancing of selectivity versus affinity of the dimerization strands. Examples of our initial inroads in using this de novo design motif in various applications include: heterodimer technology for the detection and purification of recombinant peptides and proteins; a universal dimerization domain for biosensors; a two-stage targeting and delivery system; and coiled-coils as templates for combinatorial helical libraries for basic research and drug discovery and as synthetic carrier molecules. The universality of this dimerization motif in nature suggests an endless number of possibilities for its use in de novo design, limited only by the creativity of peptide-protein engineers.

  2. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    PubMed

    Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

    2014-01-01

    In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  3. NovoTTF™-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL™ system user study.

    PubMed

    Chaudhry, Aafia; Benson, Laura; Varshaver, Michael; Farber, Ori; Weinberg, Uri; Kirson, Eilon; Palti, Yoram

    2015-11-11

    Optune™, previously known as the NovoTTF-100A System™, generates Tumor Treating Fields (TTFields), an effective anti-mitotic therapy for glioblastoma. The system delivers intermediate frequency, alternating electric fields to the supratentorial brain. Patient therapy is personalized by configuring transducer array layout placement on the scalp to the tumor site using MRI measurements and the NovoTAL System. Transducer array layout mapping optimizes therapy by maximizing electric field intensity to the tumor site. This study evaluated physician performance in conducting transducer array layout mapping using the NovoTAL System compared with mapping performed by the Novocure in-house clinical team. Fourteen physicians (7 neuro-oncologists, 4 medical oncologists, and 3 neurosurgeons) evaluated five blinded cases of recurrent glioblastoma and performed head size and tumor location measurements using a standard Digital Imaging and Communications in Medicine reader. Concordance with Novocure measurement and intra- and inter-rater reliability were assessed using relevant correlation coefficients. The study criterion for success was a concordance correlation coefficient (CCC) >0.80. CCC for each physician versus Novocure on 20 MRI measurements was 0.96 (standard deviation, SD ± 0.03, range 0.90-1.00), indicating very high agreement between the two groups. Intra- and inter-rater reliability correlation coefficients were similarly high: 0.83 (SD ±0.15, range 0.54-1.00) and 0.80 (SD ±0.18, range 0.48-1.00), respectively. This user study demonstrated an excellent level of concordance between prescribing physicians and Novocure in-house clinical teams in performing transducer array layout planning. Intra-rater reliability was very high, indicating reproducible performance. Physicians prescribing TTFields, when trained on the NovoTAL System, can independently perform transducer array layout mapping required for the initiation and maintenance of patients on TTFields therapy.

  4. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

    PubMed Central

    Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

    2013-01-01

    Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

  5. Genome sequencing of bacteria: sequencing, de novo assembly and rapid analysis using open source tools.

    PubMed

    Kisand, Veljo; Lettieri, Teresa

    2013-04-01

    De novo genome sequencing of previously uncharacterized microorganisms has the potential to open up new frontiers in microbial genomics by providing insight into both functional capabilities and biodiversity. Until recently, Roche 454 pyrosequencing was the NGS method of choice for de novo assembly because it generates hundreds of thousands of long reads (<450 bps), which are presumed to aid in the analysis of uncharacterized genomes. The array of tools for processing NGS data are increasingly free and open source and are often adopted for both their high quality and role in promoting academic freedom. The error rate of pyrosequencing the Alcanivorax borkumensis genome was such that thousands of insertions and deletions were artificially introduced into the finished genome. Despite a high coverage (~30 fold), it did not allow the reference genome to be fully mapped. Reads from regions with errors had low quality, low coverage, or were missing. The main defect of the reference mapping was the introduction of artificial indels into contigs through lower than 100% consensus and distracting gene calling due to artificial stop codons. No assembler was able to perform de novo assembly comparable to reference mapping. Automated annotation tools performed similarly on reference mapped and de novo draft genomes, and annotated most CDSs in the de novo assembled draft genomes. Free and open source software (FOSS) tools for assembly and annotation of NGS data are being developed rapidly to provide accurate results with less computational effort. Usability is not high priority and these tools currently do not allow the data to be processed without manual intervention. Despite this, genome assemblers now readily assemble medium short reads into long contigs (>97-98% genome coverage). A notable gap in pyrosequencing technology is the quality of base pair calling and conflicting base pairs between single reads at the same nucleotide position. Regardless, using draft whole genomes that are not finished and remain fragmented into tens of contigs allows one to characterize unknown bacteria with modest effort.

  6. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

    PubMed

    Warburton, Dorothy; Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-Yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-Ha; Wigler, Michael; Levy, Dan

    2014-01-01

    Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.

  7. De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

    PubMed

    Lenihan, Colin R; Liu, Sai; Deswal, Anita; Montez-Rath, Maria E; Winkelmayer, Wolfgang C

    2018-03-29

    Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. Retrospective observational cohort study. Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Three-frequency Nd:YAG laser for dental treatment

    NASA Astrophysics Data System (ADS)

    Kadlecová, Martina; Dostálová, Tat'jana; Jelínková, Helena; Němec, Michal; Å ulc, Jan; Fibrich, Martin; Bradna, Pavel; Nejezchleb, Karel; Kapitch, Nickalai; Å koda, Václav

    2018-02-01

    In the last decade, lasers found a number of indications in dentistry. However, there is still one problem: the narrow spectrum of usefulness for individual radiation wavelengths. The aim of our study is to demonstrate the use of a compact three-frequency pulsed Nd-YAG laser for more than one treatment, namely disinfection, coagulation, selective ablation, and soft tissue removal. The laser wavelengths and the maximal energies achieved were the following: 1.06 um, 1.32 um, 1.44 um and 830 mJ, 425 mJ, and 200 mJ, respectively. It has been found that all of the investigated wavelengths exhibit disinfection properties. Moreover, radiation of 1.06 um wavelength removes soft tissue and exhibits also coagulation properties. Radiation of 1.44 um is most useful for selective ablation of initial caries and disinfection, and 1.32 um radiation can be used for precise ablation when higher energy is applied.

  9. Recovery Act: Novel Kerf-Free PV Wafering that provides a low-cost approach to generate wafers from 150um to 50um in thickness

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

    Fong, Theodore E.

    2013-05-06

    The technical paper summarizes the project work conducted in the development of Kerf-Free silicon wafering equipment for silicon solar wafering. This new PolyMax technology uses a two step process of implantation and cleaving to exfoliate 50um to 120um wafers with thicknesses ranging from 50um to 120um from a 125mm or 156mm pseudo-squared silicon ingot. No kerf is generated using this method of wafering. This method of wafering contrasts with the current method of making silicon solar wafers using the industry standard wire saw equipment. The report summarizes the activity conducted by Silicon Genesis Corporation in working to develop this technologymore » further and to define the roadmap specifications for the first commercial proto-type equipment for high volume solar wafer manufacturing using the PolyMax technology.« less

  10. [POP-Q indication points, Aa and Ba, involve in diagnosis and prognosis of occult stress urinary incontinence complicated with pelvic organ prolapse].

    PubMed

    Liu, Cheng; Wu, Wenying; Yang, Qing; Hu, Ming; Zhao, Yang; Hong, Li

    2015-06-01

    To investigate the correlation between pelvic organ prolapse quantitation (POP-Q) indication points and the incidence of occult stress urinary incontinence (OSUI) and its impact on prognosis. Retrospective study medical records of 93 patients with pelvic organ prolapse (POP) staged at III-IV, of which underwent pelvic reconstruction operations with Prolift system from Jan. 2007 to Sept. 2012. None of these patients had clinical manifestations of stress urinary incontinence (SUI) before surgery, and in which 44 patients were included in study group (POP complicated with OSUI) because they were identified with OSUI, another 49 patients as control group (simple POP). Follow-up and collecting datas including POP-Q, stress test, urodynamic recordings, incidence of de novo SUI, statistic analyzing by logistic regression and receiver operating characteristic curve (ROC). (1) The study group had a much higher incidence of 30% (13/44) on de novo SUI than that of control group (4%, 2/49; P < 0.01). (2) Vaginal delivery (OR = 5.327, 95% CI: 1.120-25.347), constipation (OR = 5.789, 95% CI: 1.492-22.459), preoperative OSUI (OR = 13.695, 95% CI: 2.980-62.944), anterior vaginal wall prolapse (OR = 6.115, 95% CI: 1.231-30.379) were identified as dependent risk factors for de novo SUI by logistic regression analysis. (3) For POP patients that complicated with OSUI, we chose a cutoff value of +1.5 cm for Aa point as the threshold to predicting incidence of de novo SUI according to ROC curve, area under the curve (AUC) was 0.889 (P < 0.05), the sensitivity reached 88.9% and specificity was 73.9%. According to ROC curve of Ba point, a cutoff value of +2.5 cm was chosen as the threshold to predicting incidence of de novo SUI post-operation, it had a sensitivity of 66.7% and specificity of 82.6%, AUC was 0.766 (P < 0.05). Pre-operative OSUI is a dependent risk factor of de novo SUI for advanced POP patients. Aa and Ba points are correlated with preoperative OSUI, and it is worthy to be considered as a risk predictor on forecasting the incidence of de novo SUI post pelvic reconstruction surgery.

  11. Towards reducing the impacts of unwanted movements on identification of motion intentions.

    PubMed

    Li, Xiangxin; Chen, Shixiong; Zhang, Haoshi; Samuel, Oluwarotimi Williams; Wang, Hui; Fang, Peng; Zhang, Xiufeng; Li, Guanglin

    2016-06-01

    Surface electromyogram (sEMG) has been extensively used as a control signal in prosthesis devices. However, it is still a great challenge to make multifunctional myoelectric prostheses clinically available due to a number of critical issues associated with existing EMG based control strategy. One such issue would be the effect of unwanted movements (UMs) that are inadvertently done by users on the performance of movement classification in EMG pattern recognition based algorithms. Since UMs are not considered in training a classifier, they would decay the performance of a trained classifier in identifying the target movements (TMs), which would cause some undesired actions in control of multifunctional prostheses. In this study, the impact of UMs was systemically investigated in both able-bodied subjects and transradial amputees. Our results showed that the UMs would be unevenly classified into all classes of the TMs. To reduce the impact of the UMs on the performance of a classifier, a new training strategy that would categorize all possible UMs into a new movement class was proposed and a metric called Reject Ratio that is a measure of how many UMs is rejected by a trained classifier was adopted. The results showed that the average Reject Ratio across all the participants was greater than 91%, meanwhile the average classification accuracy of TMs was above 99% when UMs occurred. This suggests that the proposed training strategy could greatly reduce the impact of UMs on the performance of the trained classifier in identifying the TMs and may enhance the robustness of myoelectric control in clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Cometa Hyakutake (C/1996 B2): análise do gás e características físicas das partículas de poeira

    NASA Astrophysics Data System (ADS)

    Sanzovo, G. C.; de Almeida, A. A.; Boczko, R.

    2003-08-01

    A completa caracterização e compreensão do núcleo de um cometa novo é de fundamental importância para a elucidação dos processos físicos e químicos atuantes na época da formação do Sistema Solar. O Cometa Hyakutake, conjuntamente com o Cometa Hale-Bopp representam os objetos mais brilhantes que visitaram o Sistema Solar Interno nos últimos 20 anos. Neste Trabalho, nós aplicamos o Método Semi-Empírico das Magnitudes Visuais (MSEMV) à aproximadamente 4000 dados observacionais que correlacionam a magnitude visual absoluta com a distância heliocêntrica para o Cometa Hyakutake nas fases pré- e pós-periélicas. Como produto da aplicação desse método, conseguimos caracterizar dimensionalmente seu núcleo e área ativa efetiva. As taxas de produção dos radicais CN, C2 e C3, obtidos a partir de dados disponíveis na literatura, revelam que, além de muito brilhante, o Hyakutake é um cometa "normal" no sentido de Cochran (1986). Desse modo, deduzimos as taxas de perdas de água (em moléculas/s) a partir da análise de sua magnitude visual aparente, e as convertemos em taxas de perdas de gás (em g/s), despreendido pelo nucleo cometário. Com o auxílio do modelo fotométrico clássico da poeira, realizamos uma análise sistemática e uniforme dessa componente cometária, a partir dos fluxos observacionais no contínuo, para os comprimentos de onda 365,0 e 484,5 nm, assumindo que esses fluxos são o resultado da radiação solar espalhada por grãos de partículas micrométricos presentes na coma. Com isso, pudemos obter as taxas de produção (em g/s), cores (relativas à cor neutra solar), e as dimensões efetivas médias das partículas de poeira, bem como as razões poeira-gás.

  13. The use of PacBio and Hi-C data in denovo assembly of the goat genome

    USDA-ARS?s Scientific Manuscript database

    Generating de novo reference genome assemblies for non-model organisms is a laborious task that often requires a large amount of data from several sequencing platforms and cytogenetic surveys. By using PacBio sequence data and new library creation techniques, we present a de novo, high quality refer...

  14. Brief Report: Phenotypic Differences and Their Relationship to Paternal Age and Gender in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Vierck, Esther; Silverman, Jeremy M.

    2015-01-01

    Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic…

  15. De novo asymmetric synthesis and biological analysis of the daumone pheromones in Caenorhabditis elegans and in the soybean cyst nematode Heterodera glycines

    USDA-ARS?s Scientific Manuscript database

    The de novo asymmetric total syntheses of daumone 1, daumone 2 and analogs are described. The key steps of our approach are the diastereoselective palladium catalyzed glycosylation reaction, the Noyori reduction of a acetylfuran and a propargyl ketone, which introduce the absolute stereochemistry of...

  16. Canopy decline assessment in American elm after inoculation with different doses of Ophiostoma ulmi and O. novo-ulmi

    Treesearch

    Charles E. Flower; James M. Slavicek; Dale Lesser; Steven Eshita; Cornelia C. Pinchot

    2017-01-01

    Restoration of American elm (Ulmus americana L.) in natural and urban landscapes necessitates the development of new selections that not only exhibit Dutch elm disease (DED, caused by the fungal pathogen Ophiostoma novo-ulmi and O. ulmi) tolerance, but also an increase the genetic variability of tolerant...

  17. 12 CFR 543.3 - “De novo” applications for a Federal savings association charter.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false âDe novoâ applications for a Federal savings....3 “De novo” applications for a Federal savings association charter. (a) Definitions. For purposes of this section, the term “de novo association” means any Federal savings association chartered by the...

  18. Extreme-Scale De Novo Genome Assembly

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

    Georganas, Evangelos; Hofmeyr, Steven; Egan, Rob

    De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and themore » large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.« less

  19. De novo generation of plant centromeres at tandem repeats.

    PubMed

    Teo, Chee How; Lermontova, Inna; Houben, Andreas; Mette, Michael Florian; Schubert, Ingo

    2013-06-01

    Artificial minichromosomes are highly desirable tools for basic research, breeding, and biotechnology purposes. We present an option to generate plant artificial minichromosomes via de novo engineering of plant centromeres in Arabidopsis thaliana by targeting kinetochore proteins to tandem repeat arrays at non-centromeric positions. We employed the bacterial lactose repressor/lactose operator system to guide derivatives of the centromeric histone H3 variant cenH3 to LacO operator sequences. Tethering of cenH3 to non-centromeric loci led to de novo assembly of kinetochore proteins and to dicentric carrier chromosomes which potentially form anaphase bridges. This approach will be further developed and may contribute to generating minichromosomes from preselected genomic regions, potentially even in a diploid background.

  20. Whole-genome sequencing for comparative genomics and de novo genome assembly.

    PubMed

    Benjak, Andrej; Sala, Claudia; Hartkoorn, Ruben C

    2015-01-01

    Next-generation sequencing technologies for whole-genome sequencing of mycobacteria are rapidly becoming an attractive alternative to more traditional sequencing methods. In particular this technology is proving useful for genome-wide identification of mutations in mycobacteria (comparative genomics) as well as for de novo assembly of whole genomes. Next-generation sequencing however generates a vast quantity of data that can only be transformed into a usable and comprehensible form using bioinformatics. Here we describe the methodology one would use to prepare libraries for whole-genome sequencing, and the basic bioinformatics to identify mutations in a genome following Illumina HiSeq or MiSeq sequencing, as well as de novo genome assembly following sequencing using Pacific Biosciences (PacBio).

  1. CABS-fold: Server for the de novo and consensus-based prediction of protein structure.

    PubMed

    Blaszczyk, Maciej; Jamroz, Michal; Kmiecik, Sebastian; Kolinski, Andrzej

    2013-07-01

    The CABS-fold web server provides tools for protein structure prediction from sequence only (de novo modeling) and also using alternative templates (consensus modeling). The web server is based on the CABS modeling procedures ranked in previous Critical Assessment of techniques for protein Structure Prediction competitions as one of the leading approaches for de novo and template-based modeling. Except for template data, fragmentary distance restraints can also be incorporated into the modeling process. The web server output is a coarse-grained trajectory of generated conformations, its Jmol representation and predicted models in all-atom resolution (together with accompanying analysis). CABS-fold can be freely accessed at http://biocomp.chem.uw.edu.pl/CABSfold.

  2. CABS-fold: server for the de novo and consensus-based prediction of protein structure

    PubMed Central

    Blaszczyk, Maciej; Jamroz, Michal; Kmiecik, Sebastian; Kolinski, Andrzej

    2013-01-01

    The CABS-fold web server provides tools for protein structure prediction from sequence only (de novo modeling) and also using alternative templates (consensus modeling). The web server is based on the CABS modeling procedures ranked in previous Critical Assessment of techniques for protein Structure Prediction competitions as one of the leading approaches for de novo and template-based modeling. Except for template data, fragmentary distance restraints can also be incorporated into the modeling process. The web server output is a coarse-grained trajectory of generated conformations, its Jmol representation and predicted models in all-atom resolution (together with accompanying analysis). CABS-fold can be freely accessed at http://biocomp.chem.uw.edu.pl/CABSfold. PMID:23748950

  3. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma

    PubMed Central

    Landreville, Solange; Agapova, Olga A.; Matatall, Katie A.; Kneass, Zachary T.; Onken, Michael D.; Lee, Ryan S.; Bowcock, Anne M.; Harbour, J. William

    2011-01-01

    Purpose Metastasis is responsible for the death of most cancer patients, yet few therapeutic agents are available which specifically target the molecular events that lead to metastasis. We recently showed that inactivating mutations in the tumor suppressor gene BAP1 are closely associated with loss of melanocytic differentiation in uveal melanoma and metastasis (UM). The purpose of this study was to identify therapeutic agents that reverse the phenotypic effects of BAP1 loss in UM. Experimental Design In silico screens were performed to identify therapeutic compounds predicted to differentiate UM cells using Gene Set Enrichment Analysis and Connectivity Map databases. Valproic acid, trichostatin A, LBH-589 and suberoylanilide hydroxamic acid were evaluated for their effects on UM cells using morphologic evaluation, MTS viability assays, BrdU incorporation, flow cytometry, clonogenic assays, gene expression profiling, histone acetylation and ubiquitination assays, and a murine xenograft tumorigenicity model. Results HDAC inhibitors induced morphologic differentiation, cell cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. Valproic acid inhibited the growth of UM tumors in vivo. Conclusions These findings suggest that HDAC inhibitors may have therapeutic potential for inducing differentiation and prolonged dormancy of micrometastatic disease in UM. PMID:22038994

  4. Mathematisches Bewusstsein

    NASA Astrophysics Data System (ADS)

    Kaenders, Rainer; Kvasz, Ladislav

    Wenn jemand sagt, dass ein Bus um 9 Uhr abfährt - weiß man es dann? Angenommen, man ist darüber unterrichtet, dass die Busse unter der Woche immer zur vollen Stunde abfahren - von 7 Uhr morgens bis 7 Uhr abends, weiß man es dann mit dem Wissen um diese allgemeine Regel besser, dass der Bus um 9 Uhr abfährt? Macht es einen Unterschied, ob man den Fahrplan erstellt, den Bus lenkt oder nur mitfährt, um sich dieser Tatsache bewusst zu sein?

  5. VizieR Online Data Catalog: YSOs in California Molecular Cloud (Lada+, 2017)

    NASA Astrophysics Data System (ADS)

    Lada, C. J.; Lewis, J. A.; Lombardi, M.; Alves, J.

    2018-01-01

    The CMC was observed by the all-sky Planck observatory and by the Herschel Space Observatory as part of the "Auriga-California" program (Harvey et al. 2013, Cat J/ApJ/764/133). The Herschel data we used consisted of observations obtained in parallel mode simultaneously using the PACS and SPIRE instruments. For the purposes of this study we use Herschel observations made in the PACS 160um band, and the SPIRE 250um, 350um and 500um bands. (1 data file).

  6. An ethical leadership program for nursing unit managers.

    PubMed

    Jeon, Sang Hee; Park, Mihyun; Choi, Kyungok; Kim, Mi Kyoung

    2018-03-01

    The aims of this study were to evaluate the effect of an ethical leadership program (ELP) on ethical leadership, organizational citizenship behavior (OCB), and job outcomes of nursing unit managers (UMs) and to examine changes in staff nurses' perception about UMs' EL, OCB, job outcomes, and ethical work environments (EWEs) post-ELP. A quasi-experimental (pre- and post-test design) study conducted six-month intervention (ELP) using self-reported UM survey (n=44), and staff nurses (n=158) were randomly extracted by two steps. The Korean version of Ethical Leadership at Work for UMs' self-ethical leadership, the Ethical Leadership Scale for staff nurses' perceived ethical leadership, a 19-item OCB scale, and six dimensions of the medium-sized Copenhagen Psychosocial Questionnaire II for job outcomes and EWEs were administered at baseline and post-intervention. UMs' ethical leadership scores differed significantly over time in people orientation (p=0.041) and concern for ethical leadership sustainability (p=0.002) adjusting for UM experience duration and nursing unit type. Total mean and level of power-sharing of ethical leadership among UMs with <5years of UM experience improved significantly over time. Of staff nurses' perception changes about UMs' ethical leadership, OCB, job outcomes, and EWEs, significant improvement over time appeared only in EWEs' work influence level (p=0.007). This study provides useful information for clinical ELP development and examining the program's effect on leadership skills and followers' outcomes. Program facilitation relies on practical training methods, participant motivation, and assessment outcome designs by controlling clinical confounding factors. Findings have implications as an attempt for intervention to promote competencies related to ethical leadership of nursing unit managers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Predicting Survival of De Novo Metastatic Breast Cancer in Asian Women: Systematic Review and Validation Study

    PubMed Central

    Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G. M.; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M.

    2014-01-01

    Background In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. Materials and Methods We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). Results We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48–0.53) to 0.63 (95% CI, 0.60–0.66). Conclusion The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making. PMID:24695692

  8. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.

    PubMed

    O'Roak, Brian J; Vives, Laura; Girirajan, Santhosh; Karakoc, Emre; Krumm, Niklas; Coe, Bradley P; Levy, Roie; Ko, Arthur; Lee, Choli; Smith, Joshua D; Turner, Emily H; Stanaway, Ian B; Vernot, Benjamin; Malig, Maika; Baker, Carl; Reilly, Beau; Akey, Joshua M; Borenstein, Elhanan; Rieder, Mark J; Nickerson, Deborah A; Bernier, Raphael; Shendure, Jay; Eichler, Evan E

    2012-04-04

    It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.

  9. Recurrence risk in de novo structural chromosomal rearrangements.

    PubMed

    Röthlisberger, Benno; Kotzot, Dieter

    2007-08-01

    According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

  10. Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study.

    PubMed

    Buijs, Nikki; Brinkmann, Saskia J H; Oosterink, J Efraim; Luttikhold, Joanna; Schierbeek, Henk; Wisselink, Willem; Beishuizen, Albertus; van Goudoever, Johannes B; Houdijk, Alexander P J; van Leeuwen, Paul A M; Vermeulen, Mechteld A R

    2014-11-01

    Arginine plays a role in many different pathways in multiple cell types. Consequently, a shortage of arginine, caused by pathologic conditions such as cancer or injury, has the potential to disturb many cellular and organ functions. Glutamine is the ultimate source for de novo synthesis of arginine in humans via the intestinal-renal axis. Therefore, we hypothesized that parenteral glutamine supplementation may stimulate the interorgan pathway of arginine production. The objectives were to quantify arginine production from its precursor glutamine and to establish the contribution of the kidneys to de novo synthesis of arginine in patients receiving intravenous supplementation of glutamine dipeptide during major abdominal surgery. Whole-body and renal metabolism of glutamine, citrulline, and arginine was assessed by stable isotope techniques in 7 patients receiving a perioperative supplement of intravenous alanyl-glutamine (0.5 g · kg(-1) · d(-1)). Plasma glutamine, citrulline, and arginine concentrations increased significantly in patients receiving intravenous glutamine dipeptide. At whole-body level, 91% of total citrulline turnover was derived from glutamine, whereas 49% of whole-body citrulline turnover was used for de novo synthesis of arginine. The kidneys were responsible for 75% of whole-body arginine production from citrulline. Glutamine and citrulline are important sources for de novo arginine synthesis. The kidneys are the main production site for endogenous arginine. After comparison of these results with previous similar studies, our data suggest that an intravenous glutamine supplement doubles renal arginine production from citrulline. This trial was registered at www.trialregister.nl as NTR2914. © 2014 American Society for Nutrition.

  11. Evolution of sourdough microbiota in spontaneous sourdoughs started with different plant materials.

    PubMed

    Ripari, Valery; Gänzle, Michael G; Berardi, Enrico

    2016-09-02

    The preparation of sourdough in bakeries may include the use of inocula, e.g. fruits, flowers or rumen cuts to accelerate the process of selection of suitable microorganisms. The aim of this work was to investigate the effect of these inocula on the microbial evolution in sourdoughs. First, the microbiota of nineteen traditional sourdoughs that were initially started with diverse inocula was identified. Second, de novo sourdoughs were started with plant materials and the evolution of sourdough microbiota was investigated by culture, and by high-resolution melting curve quantitative PCR (HRM-qPCR). This study developed a new protocol for HRM-qPCR analysis of yeast microbiota in sourdough, and indicates this independent culture method suitable for characterization of yeasts. Microbiota of traditional sourdoughs were largely independent from the use of inoculum, however, Acetobacter spp. were identified only in sourdoughs started with apple flowers or apple pulp. In de novo sourdoughs started with plant materials, microbiota rapidly stabilized, and were characterized by Lactobacillus sanfranciscensis, Lactobacillus plantarum, Lactobacillus graminis, or Lactobacillus rossiae, and Saccharomyces cerevisiae as dominant species. Competition experiments revealed that the ecological fitness of L. plantarum, L. graminis, and L. rossiae in wheat or rye malt sourdoughs was lower when compared to L. sanfranciscensis, demonstrating that their presence in de novo sourdoughs reflects dispersal limitation. In conclusion, establishment of microbiota in de novo sourdoughs is dispersal limited. This study provides scientific support for the artisanal practice to inoculate de novo sourdoughs with flowers, berries, or related plant material. Copyright © 2016. Published by Elsevier B.V.

  12. [Our experience with recombinant activated factor VII (NovoSeven) in the high risk cardiosurgical patients with bleeding complication].

    PubMed

    Miskolczi, Szabolcs; Vaszily, Miklós; Papp, Csaba; Péterffy, Arpád

    2008-01-01

    Haemorrhagic complications significantly increase mortality and cost of treatment in cardiac surgery. A few years ago recombinant activated factor VII has been introduced to decrease such complications. In our department recombinant activated factor VII has been used in 11 patients between 2004 and 2007. Nine of them underwent a combined (simultaneous CABG and valve replacement) high risk surgery with long aortic cross clamp time and long extracorporeal circulation time. One patient underwent a repeat coronary artery bypass operation and one was operated for aortic dissection. The average dose given was 6.5 mg (2.4-9.6 mg). The average amount of bleeding without NovoSeven given was 5440 ml, however it was only 987 ml when NovoSeven was used. Nine of the patients were completely recovered and discharged from hospital, but two of them died in the postoperative period for delayed use of the recombinant factor VII-a and for severe co-morbidities (bowel ischaemia, cirrhosis of the liver). NovoSeven given in the proper time and dose significantly reduces bleeding following cardiac surgery, even if it cannot be stopped surgically. Using recombinant factor VIIa can save life in case of severe non-surgical diffuse bleeding or in case of suture insufficiency caused by friable soft tissues following high risk combined surgery with extremely long aortic cross clamp time and extracorporeal circulation time. Significant delay in the use of NovoSeven should be avoided because the temporary reduction of bleeding usually does not change fatal outcome.

  13. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

    PubMed

    Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

    2013-11-01

    Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

  14. Uridine monophosphate synthetase enables eukaryotic de novo NAD+ biosynthesis from quinolinic acid.

    PubMed

    McReynolds, Melanie R; Wang, Wenqing; Holleran, Lauren M; Hanna-Rose, Wendy

    2017-07-07

    NAD + biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD + biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD + biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD + biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of de novo NAD + biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact de novo biosynthesis pathway for NAD + from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD + levels and partially reversed NAD + -dependent phenotypes caused by mutation of pnc-1 , which encodes a nicotinamidase required for NAD + salvage biosynthesis, demonstrating contribution of de novo synthesis to NAD + homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD + biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD + biosynthesis creates novel possibilities for manipulating NAD + biosynthetic pathways, which is key for the future of therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Evaluation of 5 different labeled polymer immunohistochemical detection systems.

    PubMed

    Skaland, Ivar; Nordhus, Marit; Gudlaugsson, Einar; Klos, Jan; Kjellevold, Kjell H; Janssen, Emiel A M; Baak, Jan P A

    2010-01-01

    Immunohistochemical staining is important for diagnosis and therapeutic decision making but the results may vary when different detection systems are used. To analyze this, 5 different labeled polymer immunohistochemical detection systems, REAL EnVision, EnVision Flex, EnVision Flex+ (Dako, Glostrup, Denmark), NovoLink (Novocastra Laboratories Ltd, Newcastle Upon Tyne, UK) and UltraVision ONE (Thermo Fisher Scientific, Fremont, CA) were tested using 12 different, widely used mouse and rabbit primary antibodies, detecting nuclear, cytoplasmic, and membrane antigens. Serial sections of multitissue blocks containing 4% formaldehyde fixed paraffin embedded material were selected for their weak, moderate, and strong staining for each antibody. Specificity and sensitivity were evaluated by subjective scoring and digital image analysis. At optimal primary antibody dilution, digital image analysis showed that EnVision Flex+ was the most sensitive system (P < 0.005), with means of 8.3, 13.4, 20.2, and 41.8 gray scale values stronger staining than REAL EnVision, EnVision Flex, NovoLink, and UltraVision ONE, respectively. NovoLink was the second most sensitive system for mouse antibodies, but showed low sensitivity for rabbit antibodies. Due to low sensitivity, 2 cases with UltraVision ONE and 1 case with NovoLink stained false negatively. None of the detection systems showed any distinct false positivity, but UltraVision ONE and NovoLink consistently showed weak background staining both in negative controls and at optimal primary antibody dilution. We conclude that there are significant differences in sensitivity, specificity, costs, and total assay time in the immunohistochemical detection systems currently in use.

  16. Laminar flow assisted anisotropic bacteria absorption for chemotaxis delivery of bacteria-attached microparticle

    NASA Astrophysics Data System (ADS)

    Huh, Keon; Oh, Darong; Son, Seok Young; Yoo, Hyung Jung; Song, Byeonghwa; Cho, Dong-il Dan; Seo, Jong-Mo; Kim, Sung Jae

    2016-12-01

    The concepts of microrobots has been drawn significant attentions recently since its unprecedented applicability in nanotechnology and biomedical field. Bacteria attached microparticles presented in this work are one of pioneering microrobot technology for self-propulsion or producing kinetic energy from ambient for their motions. Microfluidic device, especially utilizing laminar flow characteristics, were employed for anisotropic attachment of Salmonella typhimurium flagellated chemotactic bacteria to 30 um × 30 um and 50 um × 50 um microparticles that made of biodegradable polymer. Any toxic chemicals or harmful treatments were excluded during the attachment process and it finished within 100 s for the anisotropic attachment. The attachments were directly confirmed by fluorescent intensity changes and SEM visualization. Chemotaxis motions were tracked using aspartate and the maximum velocity of the bacteria-attached microrobot was measured to be 5 um/s which is comparable to prior state of art technologies. This reusable and scalable method could play a key role in chemotaxis delivery of functional microparticles such as drug delivery system.

  17. 12 CFR 543.3 - “De novo” applications for a Federal savings association charter.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Office, the business of which has not been conducted previously under any charter or conducted in the... require a de novo association to have more than two million dollars in initial capital. (c) Business and... under section 5(e) of the Home Owners' Loan Act, a de novo applicant shall submit a business plan...

  18. in silico Whole Genome Sequencer & Analyzer (iWGS): a computational pipeline to guide the design and analysis of de novo genome sequencing studies

    USDA-ARS?s Scientific Manuscript database

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding it...

  19. De novo assembly of plant body plan: a step ahead of Deadpool.

    PubMed

    Kareem, Abdul; Radhakrishnan, Dhanya; Sondhi, Yash; Aiyaz, Mohammed; Roy, Merin V; Sugimoto, Kaoru; Prasad, Kalika

    2016-08-01

    While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom.

  20. Glucose-6-phosphate dehydrogenase Buenos Aires: a novel de novo missense mutation associated with severe enzyme deficiency.

    PubMed

    Minucci, Angelo; Concolino, Paola; Vendittelli, Francesca; Giardina, Bruno; Zuppi, Cecilia; Capoluongo, Ettore

    2008-06-01

    : Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the first committed steps in the pentose phosphate pathway: the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer<-->tetramer equilibrium and its stability depends on NADP(+) concentration. Herein, we report a case of a symptomatic baby affected by severe deficiency of G6PD activity due to a novel de novo genetic mutation (g1465C>T) in the thirteenth exon of its gene. : Clinical, biochemical and genetic evaluations of the affected baby and his mother were performed. : We found the g1465C>T novel mutation, in the thirteenth exon of G6PD gene (named "G6PD Buenos Aires variant"). This g1465C>T mutation produce a P489S substitution at protein level. The P489S mutation was absent in his mother, suggesting that G6PD Buenos Aires resulted from a de novo mutation. : The absence of mosaicism in the baby's DNA (from saliva and blood samples) suggests that a de novo mutation event may occur in the very early stages in embryogenesis or in the mother's germ cell lines.

  1. New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation.

    PubMed

    McLysaght, Aoife; Guerzoni, Daniele

    2015-09-26

    The origin of novel protein-coding genes de novo was once considered so improbable as to be impossible. In less than a decade, and especially in the last five years, this view has been overturned by extensive evidence from diverse eukaryotic lineages. There is now evidence that this mechanism has contributed a significant number of genes to genomes of organisms as diverse as Saccharomyces, Drosophila, Plasmodium, Arabidopisis and human. From simple beginnings, these genes have in some instances acquired complex structure, regulated expression and important functional roles. New genes are often thought of as dispensable late additions; however, some recent de novo genes in human can play a role in disease. Rather than an extremely rare occurrence, it is now evident that there is a relatively constant trickle of proto-genes released into the testing ground of natural selection. It is currently unknown whether de novo genes arise primarily through an 'RNA-first' or 'ORF-first' pathway. Either way, evolutionary tinkering with this pool of genetic potential may have been a significant player in the origins of lineage-specific traits and adaptations. © 2015 The Authors.

  2. Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid

    PubMed Central

    Menon, Deepak; Salloum, Darin; Bernfeld, Elyssa; Gorodetsky, Elizabeth; Akselrod, Alla; Frias, Maria A.; Sudderth, Jessica; Chen, Pei-Hsuan; DeBerardinis, Ralph; Foster, David A.

    2017-01-01

    mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA) interacts with the FK506-binding protein–12-rapamycin-binding (FRB) domain of mTOR, which stabilizes both mTOR complexes: mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis. We examined the impact of exogenously supplied fatty acids on mTOR in KRas-driven cancer cells, which are programmed to utilize exogenous lipids. The induction of mTOR by oleic acid was dependent upon the enzymes responsible for de novo synthesis of PA. Suppression of the de novo synthesis of PA resulted in G1 cell cycle arrest. Although it has long been appreciated that mTOR is a sensor of amino acids and glucose, this study reveals that mTOR also senses the presence of lipids via production of PA. PMID:28223357

  3. Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid.

    PubMed

    Menon, Deepak; Salloum, Darin; Bernfeld, Elyssa; Gorodetsky, Elizabeth; Akselrod, Alla; Frias, Maria A; Sudderth, Jessica; Chen, Pei-Hsuan; DeBerardinis, Ralph; Foster, David A

    2017-04-14

    mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA) interacts with the FK506-binding protein-12-rapamycin-binding (FRB) domain of mTOR, which stabilizes both mTOR complexes: mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis. We examined the impact of exogenously supplied fatty acids on mTOR in KRas-driven cancer cells, which are programmed to utilize exogenous lipids. The induction of mTOR by oleic acid was dependent upon the enzymes responsible for de novo synthesis of PA. Suppression of the de novo synthesis of PA resulted in G 1 cell cycle arrest. Although it has long been appreciated that mTOR is a sensor of amino acids and glucose, this study reveals that mTOR also senses the presence of lipids via production of PA. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

    PubMed

    Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Chen, Ming Hui; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

    2018-05-01

    Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

  5. De novo assembly of plant body plan: a step ahead of Deadpool

    PubMed Central

    Kareem, Abdul; Radhakrishnan, Dhanya; Sondhi, Yash; Aiyaz, Mohammed; Roy, Merin V.; Sugimoto, Kaoru

    2016-01-01

    Abstract While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom. PMID:27800169

  6. Inhibition of pyrimidine biosynthesis de novo in Plasmodium falciparum by 2-(4-t-butylcyclohexyl)-3-hydroxy-1,4-naphthoquinone in vitro.

    PubMed

    Hammond, D J; Burchell, J R; Pudney, M

    1985-01-01

    The effects of the hydroxynaphthoquinone BW58C on some metabolite levels and the flux of H14CO3 through the de novo pyrimidine biosynthetic pathway of intact Plasmodium falciparum have been studied in vitro using HPLC techniques. 800 nM BW58C appeared to have no significant effect on the energy status of isolated P. falciparum, but at 0.1 nM it caused a dramatic decrease in the concentrations of pyrimidine nucleotides, specifically UTP, during 256 min of incubation. Although about one hour was required to achieve a significant decrease in pyrimidine nucleotide concentrations, a much more rapid inhibition of the flux of H14CO3 through the de novo pathway was found upon addition of 0.1 nM BW58C. This inhibition caused about a 10 fold increase in the radioactivity of carbamoyl-aspartate over a 64 min period, and an overall increase in the concentration of this metabolite of about 3 fold during 256 min of incubation. These effects of BW58C against P. falciparum in vitro are discussed in terms of inhibition of de novo pyrimidine biosynthesis at the site of dihydroorotate dehydrogenase.

  7. De novo point mutations in patients diagnosed with ataxic cerebral palsy

    PubMed Central

    Parolin Schnekenberg, Ricardo; Perkins, Emma M.; Miller, Jack W.; Davies, Wayne I. L.; D’Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A.; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O’Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis

    2015-01-01

    Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. PMID:25981959

  8. Increased de novo ceramide synthesis and accumulation in failing myocardium

    PubMed Central

    Ji, Ruiping; Akashi, Hirokazu; Drosatos, Konstantinos; Liao, Xianghai; Jiang, Hongfeng; Kennel, Peter J.; Brunjes, Danielle L.; Castillero, Estibaliz; Zhang, Xiaokan; Deng, Lily Y.; Homma, Shunichi; George, Isaac J.; Takayama, Hiroo; Naka, Yoshifumi; Goldberg, Ira J.

    2017-01-01

    Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long–chain ceramides occurs in human failing myocardium, we analyzed myocardial tissue and serum from patients with severe heart failure (HF) undergoing placement of left ventricular assist devices and controls. Lipidomic analysis revealed increased total and very long–chain ceramides in myocardium and serum of patients with advanced HF. After unloading, these changes showed partial reversibility. Following myocardial infarction (MI), serine palmitoyl transferase (SPT), the rate-limiting enzyme of the de novo pathway of ceramide synthesis, and ceramides were found increased. Blockade of SPT by the specific inhibitor myriocin reduced ceramide accumulation in ischemic cardiomyopathy and decreased C16, C24:1, and C24 ceramides. SPT inhibition also reduced ventricular remodeling, fibrosis, and macrophage content following MI. Further, genetic deletion of the SPTLC2 gene preserved cardiac function following MI. Finally, in vitro studies revealed that changes in ceramide synthesis are linked to hypoxia and inflammation. In conclusion, cardiac ceramides accumulate in the failing myocardium, and increased levels are detectable in circulation. Inhibition of de novo ceramide synthesis reduces cardiac remodeling. Thus, increased de novo ceramide synthesis contributes to progressive pathologic cardiac remodeling and dysfunction. PMID:28469091

  9. Identification of the first de novo PAR1 deletion downstream of SHOX in an individual diagnosed with Léri-Weill dyschondrosteosis (LWD).

    PubMed

    Barroso, Eva; Benito-Sanz, Sara; Belinchón, Alberta; Yuste-Checa, Patricia; Gracia, Ricardo; Aragones, Angel; Campos-Barros, Angel; Heath, Karen E

    2010-01-01

    Léri-Weill dyschondrosteosis (LWD, MIM 127300), is a dominantly inherited skeletal dysplasia with disproportionate short stature, mesomelic limb shortening, and the characteristic Madelung deformity. Two regions of the pseudoautosomal region 1 (PAR1) have been shown to be involved in LWD, SHOX (short-stature homeobox-containing gene) and the downstream enhancer region. We report our genetic findings of a young girl clinically diagnosed with LWD. We analyzed the proband and her family using MLPA and microsatellite analysis. We identified a deletion, 726-866 kb in size, of the downstream SHOX enhancer region in the proband. Neither parent carried the deletion. Microsatellite analysis showed that the deleted allele was of paternal origin. The mutation is more likely to have arisen from a de novo event but paternal gonadal mosaicism cannot be excluded. In conclusion, we report the clinical and molecular details of the first case of a de novo deletion of the downstream PAR1 region in an LWD individual. De novo deletions of SHOX and the downstream enhancer region must be therefore considered in cases of isolated LWD. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  10. Incidence and long-term survival of patients with de novo head and neck carcinoma after liver transplantation.

    PubMed

    Coordes, Annekatrin; Albers, Andreas E; Lenarz, Minoo; Seehofer, Daniel; Puhl, Gero; Pascher, Andreas; Neuhaus, Ruth; Neuhaus, Peter; Pratschke, Johann; Andreou, Andreas

    2016-05-01

    Liver transplant recipients have an increased risk of developing de novo malignancies. We conducted a prospective evaluation of clinicopathological data and predictors for overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) after liver transplantation (1988 to 2010). Thirty-three of 2040 patients who underwent liver transplantation (1.6%) developed de novo HNSCC. The incidence of HNSCC in liver transplant recipients with end-stage alcoholic liver disease (26) was 5%. After a median follow-up of 9 years, 1-year, 3-year, and 5-year OS rates were 74%, 47%, and 34%, respectively. Tumor size, cervical lymph node metastases, tumor site, and therapy (surgery only vs surgery and adjuvant radiotherapy [RT]/chemoradiotherapy [CRT] vs RT/CRT only; p < .0001) were significantly associated with OS in univariate analysis. However, surgery only predicted OS independently in multivariate analysis. Early diagnosis and surgical treatment of de novo HNSCC are crucial to the outcome. HNSCC risk should be taken into close consideration during posttransplantation follow-up examinations, especially among patients with a positive history of smoking and alcohol consumption. © 2015 Wiley Periodicals, Inc.

  11. The Contribution of Mosaic Variants to Autism Spectrum Disorder.

    PubMed

    Freed, Donald; Pevsner, Jonathan

    2016-09-01

    De novo mutation is highly implicated in autism spectrum disorder (ASD). However, the contribution of post-zygotic mutation to ASD is poorly characterized. We performed both exome sequencing of paired samples and analysis of de novo variants from whole-exome sequencing of 2,388 families. While we find little evidence for tissue-specific mosaic mutation, multi-tissue post-zygotic mutation (i.e. mosaicism) is frequent, with detectable mosaic variation comprising 5.4% of all de novo mutations. We identify three mosaic missense and likely-gene disrupting mutations in genes previously implicated in ASD (KMT2C, NCKAP1, and MYH10) in probands but none in siblings. We find a strong ascertainment bias for mosaic mutations in probands relative to their unaffected siblings (p = 0.003). We build a model of de novo variation incorporating mosaic variants and errors in classification of mosaic status and from this model we estimate that 33% of mosaic mutations in probands contribute to 5.1% of simplex ASD diagnoses (95% credible interval 1.3% to 8.9%). Our results indicate a contributory role for multi-tissue mosaic mutation in some individuals with an ASD diagnosis.

  12. The contribution of de novo coding mutations to autism spectrum disorder.

    PubMed

    Iossifov, Ivan; O'Roak, Brian J; Sanders, Stephan J; Ronemus, Michael; Krumm, Niklas; Levy, Dan; Stessman, Holly A; Witherspoon, Kali T; Vives, Laura; Patterson, Karynne E; Smith, Joshua D; Paeper, Bryan; Nickerson, Deborah A; Dea, Jeanselle; Dong, Shan; Gonzalez, Luis E; Mandell, Jeffrey D; Mane, Shrikant M; Murtha, Michael T; Sullivan, Catherine A; Walker, Michael F; Waqar, Zainulabedin; Wei, Liping; Willsey, A Jeremy; Yamrom, Boris; Lee, Yoon-ha; Grabowska, Ewa; Dalkic, Ertugrul; Wang, Zihua; Marks, Steven; Andrews, Peter; Leotta, Anthony; Kendall, Jude; Hakker, Inessa; Rosenbaum, Julie; Ma, Beicong; Rodgers, Linda; Troge, Jennifer; Narzisi, Giuseppe; Yoon, Seungtai; Schatz, Michael C; Ye, Kenny; McCombie, W Richard; Shendure, Jay; Eichler, Evan E; State, Matthew W; Wigler, Michael

    2014-11-13

    Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.

  13. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

    PubMed Central

    Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

    2013-01-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  14. Gene Transfers Shaped the Evolution of De Novo NAD+ Biosynthesis in Eukaryotes

    PubMed Central

    Ternes, Chad M.; Schönknecht, Gerald

    2014-01-01

    NAD+ is an essential molecule for life, present in each living cell. It can function as an electron carrier or cofactor in redox biochemistry and energetics, and serves as substrate to generate the secondary messenger cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate. Although de novo NAD+ biosynthesis is essential, different metabolic pathways exist in different eukaryotic clades. The kynurenine pathway starting with tryptophan was most likely present in the last common ancestor of all eukaryotes, and is active in fungi and animals. The aspartate pathway, detected in most photosynthetic eukaryotes, was probably acquired from the cyanobacterial endosymbiont that gave rise to chloroplasts. An evolutionary analysis of enzymes catalyzing de novo NAD+ biosynthesis resulted in evolutionary trees incongruent with established organismal phylogeny, indicating numerous gene transfers. Endosymbiotic gene transfers probably introduced the aspartate pathway into eukaryotes and may have distributed it among different photosynthetic clades. In addition, several horizontal gene transfers substituted eukaryotic genes with bacterial orthologs. Although horizontal gene transfer is accepted as a key mechanism in prokaryotic evolution, it is supposed to be rare in eukaryotic evolution. The essential metabolic pathway of de novo NAD+ biosynthesis in eukaryotes was shaped by numerous gene transfers. PMID:25169983

  15. Efeito do Solo do Materias Organicos E do Adubo Formula 4N:14P:8K Para Producao DA Batata (Solanum tuberosum L.) Semente Pre-Basica no Casa de Vegetacao

    NASA Astrophysics Data System (ADS)

    László, Márton

    2010-05-01

    Widely well know that the potato is an important vegetable crop at Brazíl. Plant grown on about 173.000 ha, with total yield of 2.6 million tons year-1. The average yield is about 15 t ha-1. This level is very low because degeneration of crop is rapid under high temperature and high viruses pressure. Therefore seed potato propagation and production is principal on consumption potato production. This is why we found it necessary to develop it. The latossolo vermelho soil-farmyard manure- burnt rice straw-fertilizer 4N:14P:8K greenhouse pot trial was set up at the National Vegetable Crops Research Center, Brasília-DF, Brazíl in 1990. The methods of the experiments were soil x farmyard manure x burnt rice straw, soil x 4N:14P:8K fertilizer and soil x farmyard manure x burnt rice straw x 4N:14P:8K fertilizer on randomized block design in total 29 combination of treatments in 5, 5 and 3 repetitions with in a total parcel of 116. According to chemical analysis of the a., soil, b., farmyard manure and c., burnt rice straw the agrochemistry parameters were as follows: a., latossolo vermelho soil: CaCO3 0.3-0.7%, humo 0.9-1.0%, pH (H2O) 5.3, pH (KCl) 4.5, AL- P2O5 3.2-3.5 mg kg-1, AL- K2O 180 mg kg-1, Mg (KCl) 70 mg kg-1, EDTA-Zn 0.5-0.8 mg kg-1, EDTA-Cu 0.5-0.6 mg kg-1, b., farmyard manure: N 1.8 g kg-1, P2O5 2.0 g kg-1, K2O 4.0 g kg-1, c., burnt rice straw: N 0.8 g kg-1, P2O5 7.0 g kg-1, K2O 4.5 g kg-1. The experimental datas were estimated by analysis of variance, ANOVA and MANOVA. The main conclusions were as follows: 1. Mixture of 80% latossolo vermelho, 10% burnt rice straw and 10% farmyard manure were shown best performance on seed potato productivity. The piece of tubers with a 0-20 mm (consumption seeds) was increased by 77%. 2. Total seed potato number was reached maximum at 10.8 g pot-1 4N:14P:8K fertilizer regarding to average of treatments with a 33%. 3. Dry biomassa production plant-1 was decreased by high dose of 4N:14P:8K fertilizer (18.0 g pot-1) with a hard effect (57%). Our results are shown that it was possible developing of the seed potato production under tropical greenhouse conditions by optimalised soil-organic matter-fertilizer system. This datas should be as indicators to sustainable field potato advisory systems. Keywords: potato (Solanum tuberosum L.), greenhouse, latossolo vermelho soil, farmyard manure, burnt rice straw, 4N:14P:8K fertilizer, sustainability, yield RESUMO A batata é atualmente uma das hortaliças de maior importância no Brasíl. Nos conduzirémos os três experimentos para aumentár-se do produção e produtividade da batata (Solanum tuberosum L.) semente pré- básica no casa de vegetação da Brazília-DF, no Empresa Brasileira de Pesquisa Agropecuaria- Centro Nacional de Pesquisas de Hortaliças no 1990. Os três experimentos (latossolo vermelho novo x esterco de curral x palha de arroz queimado, latossolo vermelho novo x adubo 4:14:8 NPK, latossolo vermelho novo x esterco de curral x palha de arroz queimado x adubo 4:14:8 NPK) no casa de vegetação foram conduzidos com total 29 combinações, no 5-5-3 repetições com total parcelas de 116. Os resultados foram submetidos a analise de variáncia, ANOVA e MANOVA. Nossos principal resultados estam apresentándo abaixo. 1. A mistura de 80% latossolo vermelho novo, 10% palha de arroz queimado e 10% de esterco de curral, apresentou os maiores valores para numero de tuberculos com 0-20 mm, peso total de tuberculos com 0-20 mm e peso total de tuberculos por vaso. 2. Há um efeito grande crescente das doses de 4N:14P:8K nos caracteres observados. 3. Analise-se do latossolo vermelho novo x esterco de curral x palha de arroz queimado x adubo 4:14:8 NPK experimento os resultados apresentárám-se que entre nas misturas também foi melhor a 80% latossolo vermelho novo, 10% palha de arroz queimado, 10% esterco de curral. Examinando-se 15 fatores, entre 11 casos afirmou-se a mistura como para melhor que a outra mistura. Nossos resultados apresentam- se que possivel aumentar em grande volumens o produção da batata semente pré- básica com a optimalisou solo-materia orgnicânico-adubo sistema. Estes informações oferecendo-se aplicar no sustentar-se extenção rural para aumentár o produção e produtividade da bata semente e consumo. Chave palavras: batata (Solanum tuberosum L.), casa de vegetação, latossolo vermelho novo, esterco de curral, palha de arroz queimado, adubo de 4:14:8 NPK, sustentação, produção

  16. Unique Spectroscopy and Imaging of Terrestrial Planets with JWST

    NASA Astrophysics Data System (ADS)

    Villanueva, Geronimo Luis; JWST Mars Team

    2017-06-01

    In this talk, I will present the main capabilities of the James Webb Space Telescope (JWST) for performing observations of terrestrial planets, using Mars as a test case. The distinctive vantage point of JWST at the Sun-Earth Lagrange point (L2) will allow sampling the full observable disk, permitting the study of short-term phenomena, diurnal processes (across the East-West axis) and latitudinal processes between the hemispheres (including seasonal effects) with excellent spatial resolutions (0.07 arcsec at 2 um). Spectroscopic observations will be achievable in the 0.7-5 um spectral region with NIRSpec at a maximum resolving power of 2700, and with 8000 in the 1-1.25 um range. Imaging will be attainable with NIRCam at 4.3 um and with two narrow filters near 2 um, while the nightside will be accessible with several filters in the 0.5 to 2 um. Such a powerful suite of instruments will be a major asset for the exploration and characterization of Mars, and terrestrial planets in general. Some science cases include the mapping of the water D/H ratio, investigations of the Martian mesosphere via the characterization of the non-LTE CO2 emission at 4.3 um, studies of chemical transport via observations of the O2 nightglow at 1.27 um, high cadence mapping of the variability dust and water ice clouds, and sensitive searches for trace species and hydrated features on the planetary surface.

  17. Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

    PubMed Central

    Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

    2015-01-01

    Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

  18. VizieR Online Data Catalog: A dust model for bet Pic from 0.58 to 870um (Ballering+, 2016)

    NASA Astrophysics Data System (ADS)

    Ballering, N. P.; Su, K. Y. L.; Rieke, G. H.; Gaspar, A.

    2016-08-01

    β Pic was imaged with the HST/STIS CCD in coronagraphic (50CORON) mode under program GO-12551 (PI: Apai), and the results of these observations were published in Apai et al. (2015ApJ...800..136A). The instrument bandpass is set by the response of the CCD and centered at 0.58um. We searched the HST archive and found previously unpublished observations of β Pic with the WFC3 instrument in the IR channel (filter F110W at ~1.16um) from program GO-11150 (PI: Graham). The Spitzer/MIPS observations of β Pic were taken under the Spitzer Guaranteed Time Observing Program 90 (PI: M. Werner). The data at all three bands (24, 70, and 160um) are published here for the first time. Two sets of 24um observations were obtained. The first set was obtained on 2004 March 20, the second set of data was obtained on 2004 April 11. Two sets of 70um observations were obtained. The first set was obtained on 2004 April 12. The second set was obtained on 2005 April 4. Herschel/PACS 70um scan map observations of β Pic (PI G. Olofsson, observation IDs 1342186612 and 1342186613) were published by Vandenbussche et al. (2010A&A...518L.133V). We used the ALMA 870um continuum image previously published by Dent et al. (2014Sci...343.1490D). (1 data file).

  19. The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome.

    PubMed

    Selma, María V; González-Sarrías, Antonio; Salas-Salvadó, Jordi; Andrés-Lacueva, Cristina; Alasalvar, Cesarettin; Örem, Asım; Tomás-Barberán, Francisco A; Espín, Juan C

    2018-06-01

    Urolithins are microbial metabolites produced after consumption of ellagitannin-containing foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status. UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d). Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P ≤ 0.05) and intermediate-HDL-cholesterol (P ≤ 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P ≤ 0.001), apolipoprotein B (P ≤ 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P ≤ 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P ≤ 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients. UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipid-lowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM. NCT01916239 (https://clinicaltrials.gov/ct2/show/NCT01916239) and ISRCTN36468613 (http://www.isrctn.com/ISRCTN36468613). Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. De novo transcript sequence reconstruction from RNA-Seq: reference generation and analysis with Trinity

    PubMed Central

    Yassour, Moran; Grabherr, Manfred; Blood, Philip D.; Bowden, Joshua; Couger, Matthew Brian; Eccles, David; Li, Bo; Lieber, Matthias; MacManes, Matthew D.; Ott, Michael; Orvis, Joshua; Pochet, Nathalie; Strozzi, Francesco; Weeks, Nathan; Westerman, Rick; William, Thomas; Dewey, Colin N.; Henschel, Robert; LeDuc, Richard D.; Friedman, Nir; Regev, Aviv

    2013-01-01

    De novo assembly of RNA-Seq data allows us to study transcriptomes without the need for a genome sequence, such as in non-model organisms of ecological and evolutionary importance, cancer samples, or the microbiome. In this protocol, we describe the use of the Trinity platform for de novo transcriptome assembly from RNA-Seq data in non-model organisms. We also present Trinity’s supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples, and approaches to identify protein coding genes. In an included tutorial we provide a workflow for genome-independent transcriptome analysis leveraging the Trinity platform. The software, documentation and demonstrations are freely available from http://trinityrnaseq.sf.net. PMID:23845962

  1. Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in Which a Different De Novo Actg2 Gene Mutation was Detected: A Case Report.

    PubMed

    Korğalı, Elif Ünver; Yavuz, Amine; Şimşek, Cemile Ece Çağlar; Güney, Cengiz; Kurtulgan, Hande Küçük; Başer, Burak; Atalar, Mehmet Haydar; Özer, Hatice; Eğilmez, Hatice Reyhan

    2018-04-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by bladder distension without urinary tract obstruction, decreased or absent intestinal peristalsis and microcolon. Although the definitive cause remains unknown, changes in the ACTG2 gene are thought to be responsible for the intestinal and bladder hypoperistalsis. This female newborn with MMIHS had a c.532C>A /p.Arg178Ser heterozygous de novo mutation detected in the ACTG2 gene. Normal immature ganglion cells, normal calretinin punctate positivity, maintence of smooth muscle actin immunoreactivity, and decreased numbers of interstitial cells of Cajal(ICCs) were detected. This previously unreported c.532C>A /p.Arg178Ser heterozygous de novo mutation in the ACTG2 gene may lead to a severe form of MMIHS.

  2. Unit 5, STA. 50+00+RB, Orner Building, First U.M. Church Rectory, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Unit 5, STA. 50+00+RB, Orner Building, First U.M. Church Rectory, & First U.M. Church-context - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  3. VizieR Online Data Catalog: 24um excesses in clusters & membership of NGC2244 (Meng+, 2017)

    NASA Astrophysics Data System (ADS)

    Meng, H. Y. A.; Rieke, G. H.; Su, K. Y. L.; Gaspar, A.

    2017-09-01

    We re-measured the Spitzer/MIPS 24um photometry for all the clusters except for a few noted in Appendix A. We obtained the 24um data from the Spitzer Heritage Archive between 2004 Jan 28 and 2008 Oct 23. (3 data files).

  4. VizieR Online Data Catalog: X-ray AGNs with Subaru/FMOS NIR observations (Suh+, 2015)

    NASA Astrophysics Data System (ADS)

    Suh, H.; Hasinger, G.; Steinhardt, C.; Silverman, J. D.; Schramm, M.

    2016-03-01

    We performed NIR spectroscopic observations for the AGN sources with the FMOS high-resolution spectrographs on the Subaru telescope; in J-short (0.92-1.12um), J-long (1.11-1.35um), H-short (1.40-1.60um), and H-long (1.60-1.80um) coverage with a spectral resolution of R~2200. The data span the 2012 Mar 25-2013 Oct 24 period. In addition to NIR spectra, we use existing optical spectroscopy (see section 3.2). (2 data files).

  5. VizieR Online Data Catalog: MILO. I. HD 7449 radial velocities (Rodigas+, 2016)

    NASA Astrophysics Data System (ADS)

    Rodigas, T. J.; Arriagada, P.; Faherty, J.; Anglada-Escude, G.; Kaib, N.; Butler, R. P.; Shectman, S.; Weinberger, A.; Males, J. R.; Morzinski, K. M.; Close, L. M.; Hinz, P. M.; Crane, J. D.; Thompson, I.; Teske, J.; Diaz, M.; Minniti, D.; Lopez-Morales, M.; Adams, F. C.; Boss, A. P.

    2016-04-01

    We observed HD 7449 using the Magellan Clay Telescope at the Las Campanas Observatory in Chile on the nights of UT 2014 November 5 and 22. We observed the star with VisAO at Ys (0.99um) and with Clio-2 at H (1.65um) and Ks (2.15um) on the first night and with VisAO at r' (0.63um), i' (0.77um), z' (0.91um), and with Clio-2 at J (1.1um) on the second night. RV data on HD 7449 were first acquired as part of the Magellan Planet Search Program, which originally made use of the MIKE echelle spectrometer (R~70000 in the blue and ~50000 in the red; wavelength coverage ranges from 3900 to 6200Å) on the Magellan Clay telescope until 2009 September. HD 7449 was subsequently observed using the Carnegie Magellan/PFS (3880-6680Å with R~80000 in the iodine region). We also included in our analysis RVs measured with HARPS and CORALIE. These RVs were originally reported in Dumusque et al. (2011, J/A+A/535/A55). HARPS data on HD 7449 has been supplemented by the ESO archive. See section 2.2 for further explanations. (1 data file).

  6. A de novo interstitial 6q deletion in a boy with a split hand malformation.

    PubMed

    Duran-Gonzalez, Jorge; Gutierrez-Angulo, Melva; Garcia-Cruz, Diana; Ayala, Maria de la Luz; Padilla, Miguel; Davalos, Ingrid P

    2007-01-01

    We report on a de novo interstitial deletion of (6)(q15q22.2) in a 5-year-old boy with developmental delay, microcephaly, facial dysmorphism, cryptorchidism, congenital heart defect, and split-hand malformation. Previous reports and this patient suggest that 6q21 may contain a gene or genes related either directly or indirectly to limb development.

  7. De Novo whole genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 from blueberry in Georgia, USA

    USDA-ARS?s Scientific Manuscript database

    This study reports a de novo assembled draft genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 causing blueberry bacterial leaf scorch in Georgia, USA. The BB01 genome is 2,517,579 bp with a G+C content of 51.8% and 2,943 open reading frames (ORFs) and 48 RNA genes....

  8. Sequencing, De Novo Assembly, and Annotation of the Complete Genome of a New Thraustochytrid Species, Strain CCAP_4062/3

    PubMed Central

    Seddiki, Khawla; Godart, François; Aiese Cigliano, Riccardo; Sanseverino, Walter; Barakat, Mohamed; Ortet, Philippe; Rébeillé, Fabrice; Maréchal, Eric

    2018-01-01

    ABSTRACT Thraustochytrids are ecologically and biotechnologically relevant marine species. We report here the de novo assembly and annotation of the whole-genome sequence of a new thraustochytrid strain, CCAP_4062/3. The genome size was estimated at 38.7 Mb with 11,853 predicted coding sequences, and the GC content was scored at 57%. PMID:29545303

  9. Evolution of Brazilian Civil-Military Relations: From Pacted Transition to Lula’s Foreign Policy Tool

    DTIC Science & Technology

    2011-03-01

    END TO ESTADO NOVO ............................9 C. AUTHORITARIAN BRAZIL: TWENTY-ONE YEARS OF MILITARY DICTATORSHIP...Escola Superior de Guerra (Superior War College) EMFA Estado -Maior das Forcas Armadas (Joint Chiefs of Staff) FHC Fernando Henrique Cardoso MOD...Brazilian civilian-military relations literature covering the period just after the Estado Novo up to the transition to democracy. This will highlight

  10. De Novo mRNA Synthesis Is Required for Both Consolidation and Reconsolidation of Fear Memories in the Amygdala

    ERIC Educational Resources Information Center

    Duvarci, Sevil; Nader, Karim; LeDoux, Joseph E.

    2008-01-01

    Memory consolidation is the process by which newly learned information is stabilized into long-term memory (LTM). Considerable evidence indicates that retrieval of a consolidated memory returns it to a labile state that requires it to be restabilized. Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in…

  11. 76 FR 58812 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-22

    ..., New Mexico; to engage de novo through Bank'34, Alamogordo, New Mexico, in acquiring and holding... LL (12 CFR part 238) or Regulation MM (12 CFR part 239) to engage de novo, or to acquire or control... October 7, 2011. A. Federal Reserve Bank of Dallas (E. Ann Worthy, Vice President) 2200 North Pearl Street...

  12. High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 3. Chemical Stability and Visual Appearance of a Protein-Based Aqueous Solution for Injection as a Function of HVLD Exposure.

    PubMed

    Rasmussen, Mats; Damgaard, Rasmus; Buus, Peter; Guazzo, Dana Morton

    2013-01-01

    This Part 3 of this three-part research series reports the impact of high-voltage leak detection (HVLD) exposure on the physico-chemical stability of the packaged product. The product, intended for human administration by injection, is an aqueous solution formulation of the rapid acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. The package is a small-volume form-fill-seal plastic laminate bag. Product-packages exposed to HVLD were compared to unexposed product after storage for 9 months at recommended storage conditions of 5 ± 3 °C. No differences in active ingredient or degradation products assays were noted. No changes in any other stability indicating parameter results were observed. This report concludes this three-part series. Part 1 documented HVLD method development and validation work. Part 2 explored the impact of various package material, package temperature, and package storage conditions on HVLD test results. Detection of leaks in the bag seal area was investigated. In conclusion, HVLD is reported to be a validatable leak test method suitable for rapid, nondestructive container-closure integrity evaluation of the subject product-package. In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was proven to find hole leaks in small plastic bags filled with a solution of insulin aspart intended for human injection (NovoRapid®/NovoLog® by Novo Nordisk A/S, Bagsværd, Denmark). In Part 2, the ability of the HVLD method to find other types of package leaks was tested, and the impact of package material and product storage temperature on HVLD results was explored. This final Part 3 checked how well the packaged protein drug solution maintained its potency after HVLD exposure over 9 months of storage under long-term stability conditions. Results showed that HVLD caused no harm to the product.

  13. Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

    PubMed

    Chiosea, Simion I; Thompson, Lester D R; Weinreb, Ilan; Bauman, Julie E; Mahaffey, Alyssa M; Miller, Caitlyn; Ferris, Robert L; Gooding, William E

    2016-10-15

    The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society. © 2016 American Cancer Society.

  14. Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men.

    PubMed

    Aarsland, A; Wolfe, R R

    1998-06-01

    Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state, and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate-enriched diet (approximately 2.5 times energy expenditure). The secretion of de novo palmitate was increased 15- and 43-fold after 1 and 4 days of hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0 micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/-0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal), 28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease the secretion while 4 days increased the secretion of all preformed FA in VLDL TG. The rate of secretion of preformed palmitate and oleate were almost identical (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1 micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and 356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted for 80-90% of the secretion from the preformed source. Palmitate is the predominant product of acute and prolonged carbohydrate mediated lipogenesis in the human liver. The pathway of further elongation and subsequent desaturation of de novo synthesized palmitate to generate stearate and oleate is inducible but, quantitatively, of minor significance in hepatic lipogenesis.

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

    Pang, Jinsong, E-mail: pangjs542@nenu.edu.cn; Dong, Mingyue; Li, Ning

    Highlights: ► A rice de novo DNA methyltransferase OsDRM2 was cloned. ► In vitro methylation activity of OsDRM2 was characterized with Escherichia coli. ► Assays of OsDRM2 in vivo methylation were done with Saccharomyces cerevisiae. ► OsDRM2 methylation activity is not preferential to any type of cytosine context. ► The activity of OsDRM2 is independent of RdDM pathway. - Abstract: DNA methylation of cytosine nucleotides is an important epigenetic modification that occurs in most eukaryotic organisms and is established and maintained by various DNA methyltransferases together with their co-factors. There are two major categories of DNA methyltransferases: de novo andmore » maintenance. Here, we report the isolation and functional characterization of a de novo methyltransferase, named OsDRM2, from rice (Oryza sativa L.). The full-length coding region of OsDRM2 was cloned and transformed into Escherichia coli and Saccharomyces cerevisiae. Both of these organisms expressed the OsDRM2 protein, which exhibited stochastic de novo methylation activity in vitro at CG, CHG, and CHH di- and tri-nucleotide patterns. Two lines of evidence demonstrated the de novo activity of OsDRM2: (1) a 5′-CCGG-3′ containing DNA fragment that had been pre-treated with OsDRM2 protein expressed in E. coli was protected from digestion by the CG-methylation-sensitive isoschizomer HpaII; (2) methylation-sensitive amplified polymorphism (MSAP) analysis of S. cerevisiae genomic DNA from transformants that had been introduced with OsDRM2 revealed CG and CHG methylation levels of 3.92–9.12%, and 2.88–6.93%, respectively, whereas the mock control S. cerevisiae DNA did not exhibit cytosine methylation. These results were further supported by bisulfite sequencing of the 18S rRNA and EAF5 genes of the transformed S. cerevisiae, which exhibited different DNA methylation patterns, which were observed in the genomic DNA. Our findings establish that OsDRM2 is an active de novo DNA methyltransferase gene with conserved activity in both prokaryotic and eukaryotic non-host species.« less

  16. Utility of Serum Creatinine, Creatine Kinase and Urinary Myoglobin in Detecting Acute Renal Failure due to Rhabdomyolysis in Trauma and Electrical Burns Patients.

    PubMed

    Bhavsar, Preetish; Rathod, Kirtikumar Jagdish; Rathod, Darshana; Chamania, C S

    2013-02-01

    Rhabdomyolysis due to trauma and burns is an important cause of acute renal failure (ARF) secondary to myoglobinuria. To prevent morbidity and mortality from ARF due to rhabdomyolysis, early detection of ARF by monitoring the biochemical parameters such as serum creatinine, serum creatine kinase (CK), and urinary myoglobin (UM) can be helpful. The aims of the study were (1) to detect ARF due to rhabdomyolysis using serum creatinine, serum CK, and UM in trauma and electrical burn patients (2) to compare utility of these parameters in early prediction of ARF in patients of rhabdomyolysis. A total of 50 patients with trauma and electrical burns were included in the study. Serum creatinine, serum CK, and UM measurements were done at the time of admission and after 48 h. Diagnosis of ARF was made in the patients by Rifle's criteria. The presence of significant elevation of creatinine, serum CK, and UM at the time of admission and after 48 h was compared in patients developing ARF by Fisher's exact test. Fifteen of the 50 patients developed ARF as per the defined criteria. Of these, 9 patients (60 %) had raised level of serum creatinine above 1.4 mg% at admission and 14 patients (93.33 %) had CK level >1250 U/L at admission, whereas UM was positive in 6 (40 %) patients. Serum creatinine was significantly raised in all of the 15 ARF patients (100 %) after 48 h of admission and serum CK was raised in 14 of the 15 ARF patients (93.33 %). UM was negative in all the patients after 48 h of admission. Statistical analysis showed that rise in serum CK on admission was significantly increased in patients developing ARF as compared with serum creatinine and UM (P < 0.0001). On admission, CK is a better predictor of ARF due to rhabdomyolysis than creatinine and UM. Initial creatinine is a better predictor of ARF due to rhabdomyolysis than UM. UM assay is not a good investigation for early prediction of ARF in rhabdomyolysis.

  17. Ga Lithography in Sputtered Niobium for Superconductive Micro and Nanowires.

    DOE PAGES

    Henry, Michael David; Lewis, Rupert M.; Wolfley, Steven L.; ...

    2014-08-18

    This work demonstrates the use of FIB implanted Ga as a lithographic mask for plasma etching of Nb films. Using a highly collimated Ga beam of a FIB, Nb is implanted 12 nm deep with a 14 nm thick Ga layer providing etch selectivity better than 15:1 with fluorine based etch chemistry. Implanted square test patterns, both 10 um by and 10 um and 100 um by 100 um, demonstrate that doses above than 7.5 x 1015 cm-2 at 30 kV provide adequate mask protection for a 205 nm thick, sputtered Nb film. The resolution of this dry lithographic techniquemore » is demonstrated by fabrication of nanowires 75 nm wide by 10 um long connected to 50 um wide contact pads. The residual resistance ratio of patterned Nb films was 3. The superconducting transition temperature, Tc =7.7 K, was measured using MPMS. This nanoscale, dry lithographic technique was extended to sputtered TiN and Ta here and could be used on other fluorine etched superconductors such as NbN, NbSi, and NbTi.« less

  18. Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

    PubMed

    Tao, Li; Chu, Laura; Wang, Lisa I; Moy, Lisa; Brammer, Melissa; Song, Chunyan; Green, Marjorie; Kurian, Allison W; Gomez, Scarlett L; Clarke, Christina A

    2016-09-01

    To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression. We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality. Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer. De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

  19. Stimulated Nitric Oxide Production and Arginine Deficiency in Cystic Fibrosis Children with Nutritional Failure

    PubMed Central

    Engelen, Mariëlle PKJ; Com, Gulnur; Luiking, Yvette C; Deutz, Nicolaas EP

    2013-01-01

    Objective Reduced nitric oxide (NO) concentrations are found in the airways of many patients with cystic fibrosis (CF) and are associated with increased airflow obstruction. We determined whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide production in pediatric patients with CF and nutritional failure. Study design In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline, and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Results Increased arginine clearance was found in patients with CF (p<0.001) whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P<0.001), de novo arginine synthesis, and protein breakdown and synthesis (P<0.05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n=7) had significantly higher NO production (P<0.05), de novo arginine synthesis, citrulline production (P<0.001), and plasma citrulline concentration (P<0.05) and lower plasma arginine concentration (P<0.05) than those without nutritional failure (n=9). Conclusions Nutritional failure in CF is associated with increased NO production. However, upregulation of de novo arginine synthesis and citrulline production was not sufficient to meet the increased arginine needs leading to arginine deficiency. PMID:23419590

  20. Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.

    PubMed

    Leppa, Virpi M; Kravitz, Stephanie N; Martin, Christa Lese; Andrieux, Joris; Le Caignec, Cedric; Martin-Coignard, Dominique; DyBuncio, Christina; Sanders, Stephan J; Lowe, Jennifer K; Cantor, Rita M; Geschwind, Daniel H

    2016-09-01

    Rare mutations, including copy-number variants (CNVs), contribute significantly to autism spectrum disorder (ASD) risk. Although their importance has been established in families with only one affected child (simplex families), the contribution of both de novo and inherited CNVs to ASD in families with multiple affected individuals (multiplex families) is less well understood. We analyzed 1,532 families from the Autism Genetic Resource Exchange (AGRE) to assess the impact of de novo and rare CNVs on ASD risk in multiplex families. We observed a higher burden of large, rare CNVs, including inherited events, in individuals with ASD than in their unaffected siblings (odds ratio [OR] = 1.7), but the rate of de novo events was significantly lower than in simplex families. In previously characterized ASD risk loci, we identified 49 CNVs, comprising 24 inherited events, 19 de novo events, and 6 events of unknown inheritance, a significant enrichment in affected versus control individuals (OR = 3.3). In 21 of the 30 families (71%) in whom at least one affected sibling harbored an established ASD major risk CNV, including five families harboring inherited CNVs, the CNV was not shared by all affected siblings, indicating that other risk factors are contributing. We also identified a rare risk locus for ASD and language delay at chromosomal region 2q24 (implicating NR4A2) and another lower-penetrance locus involving inherited deletions and duplications of WWOX. The genetic architecture in multiplex families differs from that in simplex families and is complex, warranting more complete genetic characterization of larger multiplex ASD cohorts. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. Effects of exogenous fatty acids and inhibition of de novo fatty acid synthesis on disaturated phosphatidylcholine production by fetal lung cells and adult type II cells.

    PubMed

    Maniscalco, W M; Finkelstein, J N; Parkhurst, A B

    1989-05-01

    De novo fatty acid synthesis may be an important source of saturated fatty acids for fetal lung disaturated phosphatidylcholine (DSPC) production. To investigate the roles of de novo fatty acid synthesis and exogenous fatty acids, we incubated dispersed fetal lung cells and freshly isolated adult type II cells with exogenous palmitate and oleate and measured DSPC synthesis. Unlike adult type II cells, fetal lung cells did not increase DSPC synthesis when exogenous palmitate was available; adult type II cells increased DSPC synthesis by 70% in the presence of palmitate. Exogenous oleate decreased DSPC synthesis by 48% in fetal cells but not in adult type II cells. Incubation of fetal lung cells with TOFA [2-furancarboxylate, 5-(tetradecyloxy)-sodium], a metabolic inhibitor of fatty acid synthesis, decreased fatty acid synthesis by 65%. There was a simultaneous 56% inhibition of DSPC production, but no effect on protein, DNA, or glyceride-glycerol production, measured by precursor incorporation. The inhibition of DSPC synthesis associated with TOFA was partially prevented by exogenous palmitate but not oleate. Fetal cells prepared from explants that had been cultured in dexamethasone also had TOFA-associated inhibition of DSPC synthesis that was similar to non-dexamethasone-exposed cells. These studies suggest that under baseline conditions of low fatty acid availability, such as in the fetus, de novo fatty acid synthesis in fetal cells, but not in adult type II cells, provides sufficient saturated fatty acids to support maximal DSPC production. Inhibition of de novo fatty acid synthesis resulting in decreased DSPC production in fetal lung cells in conditions of low fatty acid availability suggests that fatty acid synthesis may be central to maintain DSPC synthesis in the fetus.

  2. Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

    PubMed

    Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

    2016-12-01

    : Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

  3. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

    PubMed Central

    2010-01-01

    Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTRinh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. De novo cholesterol synthesis contributes to membrane cholesterol accessibility. Conclusions The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in de novo cholesterol synthesis to restore membrane content. PMID:20487541

  4. Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens.

    PubMed

    Grant, M B; Wargovich, T J; Ellis, E A; Tarnuzzer, R; Caballero, S; Estes, K; Rossing, M; Spoerri, P E; Pepine, C

    1996-12-17

    The molecular and cellular processes that induce rapid atherosclerotic plaque progression in patients with unstable angina and initiate restenosis following coronary interventional procedures are uncertain. We examined primary (de novo) and restenotic lesions retrieved at the time of directional coronary atherectomy for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its receptor and binding proteins were not detected in SMCs of normal coronary arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I receptor was significantly higher in de novo lesions as compared to restenotic lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P < 0.05, respectively). IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5 localized in the cytoplasm of sSMCs and in the extracellular matrix. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) performed on de novo atherectomy specimens identified mRNA for IGF-I, IGF-I receptor, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 levels and detected mRNA for IGFBP-3. The expression of IGF-I, IGF-I receptor, and IGFBPs in atherectomy plaques suggests that the development of coronary obstructive lesions may be a result of changes in the IGF system.

  5. Arginine de novo and nitric oxide production in disease states

    PubMed Central

    Luiking, Yvette C.; Ten Have, Gabriella A. M.; Wolfe, Robert R.

    2012-01-01

    Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin (BH4) is an essential and rate-limiting cofactor for the production of NO. Depletion of BH4 in oxidative-stressed endothelial cells can result in so-called NOS3 “uncoupling,” resulting in production of superoxide instead of NO. Moreover, distribution of arginine between intracellular transporters and arginine-converting enzymes, as well as between the arginine-converting and arginine-synthesizing enzymes, determines the metabolic fate of arginine. Alternatively, NO can be derived from conversion of nitrite. Reduced arginine availability stemming from reduced de novo production and elevated arginase activity have been reported in various conditions of acute and chronic stress, which are often characterized by increased NOS2 and reduced NOS3 activity. Cardiovascular and pulmonary disorders such as atherosclerosis, diabetes, hypercholesterolemia, ischemic heart disease, and hypertension are characterized by NOS3 uncoupling. Therapeutic applications to influence (de novo) arginine and NO metabolism aim at increasing substrate availability or at influencing the metabolic fate of specific pathways related to NO bioavailability and prevention of NOS3 uncoupling. These include supplementation of arginine or citrulline, provision of NO donors including inhaled NO and nitrite (sources), NOS3 modulating agents, or the targeting of endogenous NOS inhibitors like asymmetric dimethylarginine. PMID:23011059

  6. Effective de novo assembly of fish genome using haploid larvae.

    PubMed

    Iwasaki, Yuki; Nishiki, Issei; Nakamura, Yoji; Yasuike, Motoshige; Kai, Wataru; Nomura, Kazuharu; Yoshida, Kazunori; Nomura, Yousuke; Fujiwara, Atushi; Kobayashi, Takanori; Ototake, Mitsuru

    2016-02-01

    Recent improvements in next-generation sequencing technology have made it possible to do whole genome sequencing, on even non-model eukaryote species with no available reference genomes. However, de novo assembly of diploid genomes is still a big challenge because of allelic variation. The aim of this study was to determine the feasibility of utilizing the genome of haploid fish larvae for de novo assembly of whole-genome sequences. We compared the efficiency of assembly using the haploid genome of yellowtail (Seriola quinqueradiata) with that using the diploid genome obtained from the dam. De novo assembly from the haploid and the diploid sequence reads (100 million reads per each datasets) generated by the Ion Proton sequencer (200 bp) was done under two different assembly algorithms, namely overlap-layout-consensus (OLC) and de Bruijn graph (DBG). This revealed that the assembly of the haploid genome significantly reduced (approximately 22% for OLC, 9% for DBG) the total number of contigs (with longer average and N50 contig lengths) when compared to the diploid genome assembly. The haploid assembly also improved the quality of the scaffolds by reducing the number of regions with unassigned nucleotides (Ns) (total length of Ns; 45,331,916 bp for haploids and 67,724,360 bp for diploids) in OLC-based assemblies. It appears clear that the haploid genome assembly is better because the allelic variation in the diploid genome disrupts the extension of contigs during the assembly process. Our results indicate that utilizing the genome of haploid larvae leads to a significant improvement in the de novo assembly process, thus providing a novel strategy for the construction of reference genomes from non-model diploid organisms such as fish. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

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

    Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au; Drew, Simon C., E-mail: sdrew@unimelb.edu.au

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methodsmore » that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.« less

  8. Myocardial Injury after Percutaneous Coronary Intervention for In-Stent Restenosis Versus de novo Stenosis.

    PubMed

    Shimonaga, Takashi; Kurisu, Satoshi; Watanabe, Noriaki; Ikenaga, Hiroki; Higaki, Tadanao; Iwasaki, Toshitaka; Ishibashi, Ken; Dohi, Yoshihiro; Fukuda, Yukihiro; Kihara, Yasuki

    2015-01-01

    Periprocedural myocardial injury (PMI) remains a relatively common complication even after successful procedures. In-stent restenosis (ISR) may be involved in lesion-related factors for PMI. We compared the incidence of PMI between patients with ISR and those with de novo stenosis. The study population consisted of 121 patients with coronary artery disease who had been treated with statins and subsequently underwent angiographically successful percutaneous coronary intervention (PCI). Blood samples for troponin I were collected 18 to 24 hours after PCI. PMI was defined as an increase in the troponin I levels greater than 0.15 ng/mL. Major PMI was defined as an increase in the troponin I levels greater than 0.75 ng/mL. There were 34 patients with ISR and 87 patients with de novo stenosis. The incidence of PMI was similar between the two groups (47.1 % vs. 55.2 %, p=0.42). Among the patients with ISR, the incidences of PMI were 33.3 %, 60.0 % and 66.7 % in patients with focal ISR, diffuse ISR and diffuse proliferative ISR, respectively, although these differences were not statistically significant. The incidence of major PMI was significantly less frequent in patients with ISR than those with de novo stenosis (5.9 % vs. 25.3 %, p=0.03). A multivariate logistic regression analysis showed that ISR [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.03-0.90; p=0.03] and the maximum inflation pressure (OR 1.15, 95% CI 1.04-1.30; p=0.009) were independent predictors of major PMI. Our results suggest that while PMI occurs in patients with ISR as commonly as those with de novo stenosis, major PMI occurs less frequently in patients with ISR.

  9. Cruise ship environmental hygiene and the risk of norovirus infection outbreaks: an objective assessment of 56 vessels over 3 years.

    PubMed

    Carling, Philip C; Bruno-Murtha, Lou Ann; Griffiths, Jeffrey K

    2009-11-01

    Norovirus infection outbreaks (NoVOs) occur frequently in closed populations, such as cruise ship passengers. Environmental contamination is believed to play an important role in NoVO propagation. Trained health care professionals covertly evaluated the thoroughness of disinfection cleaning (TDC) of 6 standardized objects (toilet seat, flush handle or button, toilet stall inner handhold, stall inner door handle, restroom inner door handle, and baby changing table surfaces) with high potential for fecal contamination in cruise ship public restrooms, by means of a previously validated novel targeting method. Fifty-six cruise ships (approximately 30% of 180 vessels operated by 9 large cruise lines) were evaluated from July 2005 through August 2008. Overall, 37% (range, 4%-100%; 95% confidence interval, 29.2%-45.4%) of 8344 objects in 273 randomly selected public restrooms were cleaned daily. The TDC did not differ by cruise line and did not correlate with the Centers for Disease Control and Prevention (CDC) Vessel Sanitation Program inspection scores (r(2), .002; P = .75). More than half the vessels had overall TDC scores <30%, although several of these low-scoring ships had near-perfect CDC sanitation scores. The mean TDC of the 3 ships evaluated within 4 months before a NoVO (10.3%) was substantially less than the mean TDC of the 40 ships that did not experience NoVOs (40.4%) (P < .004). An objective evaluation of public restroom environmental hygiene on 56 cruise ships found that only 37% of selected toilet area objects were cleaned on a daily basis. Low TDC scores may predict subsequent NoVO-prone vessels. Enhanced public restroom cleaning may prevent or moderate NoVOs on cruise ships.

  10. Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis.

    PubMed

    Mouchli, Mohamad A; Singh, Siddharth; Loftus, Edward V; Boardman, Lisa; Talwalkar, Jayant; Rosen, Charles B; Heimbach, Julie K; Wiesner, Russell H; Hasan, Bashar; Poterucha, John J; Kymberly, Watt D

    2017-08-01

    Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT. All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT. Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy. The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.

  11. Proteome analysis reveals that de novo regenerated mucosa over fibula flap-reconstructed mandibles resembles mature keratinized oral mucosa.

    PubMed

    Kumar, Vinay V; James, Bonney L; Ruß, Manuela; Mikkat, Stefan; Suresh, Amritha; Kämmerer, Peer W; Glocker, Michael O

    2018-03-01

    The aim of this study was to determine whether intra-oral de novo regenerated mucosa (D) that grew over free fibula flap reconstructed-mandibles resembled the donor tissue i.e. external skin (S) of the lateral leg, or the recipient site tissue, i.e. keratinized oral mucosa (K). Differential proteome analysis was performed with ten tissue samples from each of the three groups: de novo regenerated mucosa (D), external skin (S), and keratinized oral mucosa (K). Expression differences of cornulin and involucrin were validated by Western blot analysis and their spatial distributions in the respective tissues were ascertained by immunohistochemistry. From all three investigated tissue types a total of 1188 proteins were identified, 930 of which were reproducibly and robustly quantified by proteome analysis. The best differentiating proteins were assembled in an oral mucosa proteome signature that encompasses 56 differentially expressed proteins. Principal component analysis of both, the 930 quantifiable proteins and the 56 oral mucosa signature proteins revealed that the de novo regenerated mucosa resembles keratinized oral mucosa much closer than extra-oral skin. Differentially expressed cornification-related proteins comprise proteins from all subclasses of the cornified cell envelope. Prominently expressed in intra-oral mucosa tissues were (i) cornifin-A, cornifin-B, SPRR3, and involucrin from the cornified-cell-envelope precursor group, (ii) S100A9, S100A8 and S100A2 from the S100 group, and (iii) cornulin which belongs to the fused-gene-protein group. According to its proteome signature de novo regenerated mucosa over the free fibula flap not only presents a passive structural surface layer but has adopted active tissue function. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. What is the incidence of kidney stones after chemotherapy in patients with lymphoproliferative or myeloproliferative disorders?

    PubMed

    Mirheydar, Hossein S; Banapour, Pooya; Massoudi, Rustin; Palazzi, Kerrin L; Jabaji, Ramzi; Reid, Erin G; Millard, Frederick E; Kane, Christopher J; Sur, Roger L

    2014-01-01

    This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

  13. Safety and effectiveness of room temperature stable recombinant factor VIIa in patients with haemophilia A or B and inhibitors: Results of a multinational, prospective, observational study.

    PubMed

    Kavakli, K; Demartis, F; Karimi, M; Eshghi, P; Neme, D; Chambost, H; Sommer, L; Zak, M; Benson, G

    2017-07-01

    A room temperature stable formulation of recombinant activated factor VII (NovoSeven ® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven ® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. SMART-7™ was designed to investigate the safety of NovoSeven ® in a real-world setting in patients with haemophilia A or B with inhibitors. Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven ® monotherapy, 94.2% stopped by end of treatment. Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven ® under real-world conditions. © 2017 John Wiley & Sons Ltd.

  14. A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect

    PubMed Central

    McEntagart, Meriel; Williamson, Kathleen A.; Rainger, Jacqueline K.; Wheeler, Ann; Seawright, Anne; De Baere, Elfride; Verdin, Hannah; Bergendahl, L. Therese; Quigley, Alan; Rainger, Joe; Dixit, Abhijit; Sarkar, Ajoy; López Laso, Eduardo; Sanchez-Carpintero, Rocio; Barrio, Jesus; Bitoun, Pierre; Prescott, Trine; Riise, Ruth; McKee, Shane; Cook, Jackie; McKie, Lisa; Ceulemans, Berten; Meire, Françoise; Temple, I. Karen; Prieur, Fabienne; Williams, Jonathan; Clouston, Penny; Németh, Andrea H.; Banka, Siddharth; Bengani, Hemant; Handley, Mark; Freyer, Elisabeth; Ross, Allyson; van Heyningen, Veronica; Marsh, Joseph A.; Elmslie, Frances; FitzPatrick, David R.

    2016-01-01

    Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions. PMID:27108798

  15. Rapid hybrid de novo assembly of a microbial genome using only short reads: Corynebacterium pseudotuberculosis I19 as a case study.

    PubMed

    Cerdeira, Louise Teixeira; Carneiro, Adriana Ribeiro; Ramos, Rommel Thiago Jucá; de Almeida, Sintia Silva; D'Afonseca, Vivian; Schneider, Maria Paula Cruz; Baumbach, Jan; Tauch, Andreas; McCulloch, John Anthony; Azevedo, Vasco Ariston Carvalho; Silva, Artur

    2011-08-01

    Due to the advent of the so-called Next-Generation Sequencing (NGS) technologies the amount of monetary and temporal resources for whole-genome sequencing has been reduced by several orders of magnitude. Sequence reads can be assembled either by anchoring them directly onto an available reference genome (classical reference assembly), or can be concatenated by overlap (de novo assembly). The latter strategy is preferable because it tends to maintain the architecture of the genome sequence the however, depending on the NGS platform used, the shortness of read lengths cause tremendous problems the in the subsequent genome assembly phase, impeding closing of the entire genome sequence. To address the problem, we developed a multi-pronged hybrid de novo strategy combining De Bruijn graph and Overlap-Layout-Consensus methods, which was used to assemble from short reads the entire genome of Corynebacterium pseudotuberculosis strain I19, a bacterium with immense importance in veterinary medicine that causes Caseous Lymphadenitis in ruminants, principally ovines and caprines. Briefly, contigs were assembled de novo from the short reads and were only oriented using a reference genome by anchoring. Remaining gaps were closed using iterative anchoring of short reads by craning to gap flanks. Finally, we compare the genome sequence assembled using our hybrid strategy to a classical reference assembly using the same data as input and show that with the availability of a reference genome, it pays off to use the hybrid de novo strategy, rather than a classical reference assembly, because more genome sequences are preserved using the former. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    PubMed

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  17. Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors

    PubMed Central

    Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E.; Cao, Mengjun

    2016-01-01

    Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. Significance In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. PMID:27458264

  18. De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline craniosynostosis.

    PubMed

    Timberlake, Andrew T; Furey, Charuta G; Choi, Jungmin; Nelson-Williams, Carol; Loring, Erin; Galm, Amy; Kahle, Kristopher T; Steinbacher, Derek M; Larysz, Dawid; Persing, John A; Lifton, Richard P

    2017-08-29

    Non-syndromic craniosynostosis (NSC) is a frequent congenital malformation in which one or more cranial sutures fuse prematurely. Mutations causing rare syndromic craniosynostoses in humans and engineered mouse models commonly increase signaling of the Wnt, bone morphogenetic protein (BMP), or Ras/ERK pathways, converging on shared nuclear targets that promote bone formation. In contrast, the genetics of NSC is largely unexplored. More than 95% of NSC is sporadic, suggesting a role for de novo mutations. Exome sequencing of 291 parent-offspring trios with midline NSC revealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP, and Ras/ERK signaling (10.9-fold enrichment, P = 2.4 × 10 -11 ). SMAD6 had 4 de novo and 14 transmitted mutations; no other gene had more than 1. Four familial NSC kindreds had mutations in genes previously implicated in syndromic disease. Collectively, these mutations contribute to 10% of probands. Mutations are predominantly loss-of-function, implicating haploinsufficiency as a frequent mechanism. A common risk variant near BMP2 increased the penetrance of SMAD6 mutations and was overtransmitted to patients with de novo mutations in other genes in these pathways, supporting a frequent two-locus pathogenesis. These findings implicate new genes in NSC and demonstrate related pathophysiology of common non-syndromic and rare syndromic craniosynostoses. These findings have implications for diagnosis, risk of recurrence, and risk of adverse neurodevelopmental outcomes. Finally, the use of pathways identified in rare syndromic disease to find genes accounting for non-syndromic cases may prove broadly relevant to understanding other congenital disorders featuring high locus heterogeneity.

  19. Sequencing proteins with transverse ionic transport in nanochannels.

    PubMed

    Boynton, Paul; Di Ventra, Massimiliano

    2016-05-03

    De novo protein sequencing is essential for understanding cellular processes that govern the function of living organisms and all sequence modifications that occur after a protein has been constructed from its corresponding DNA code. By obtaining the order of the amino acids that compose a given protein one can then determine both its secondary and tertiary structures through structure prediction, which is used to create models for protein aggregation diseases such as Alzheimer's Disease. Here, we propose a new technique for de novo protein sequencing that involves translocating a polypeptide through a synthetic nanochannel and measuring the ionic current of each amino acid through an intersecting perpendicular nanochannel. We find that the distribution of ionic currents for each of the 20 proteinogenic amino acids encoded by eukaryotic genes is statistically distinct, showing this technique's potential for de novo protein sequencing.

  20. Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

    PubMed

    Carecchio, Miryam; Picillo, Marina; Valletta, Lorella; Elia, Antonio E; Haack, Tobias B; Cozzolino, Autilia; Vitale, Annalisa; Garavaglia, Barbara; Iuso, Arcangela; Bagella, Caterina F; Pappatà, Sabina; Barone, Paolo; Prokisch, Holger; Romito, Luigi; Tiranti, Valeria

    2017-07-01

    Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.

  1. VizieR Online Data Catalog: Reflectance spectra of 12 Trojans and Hildas (Marsset+, 2014)

    NASA Astrophysics Data System (ADS)

    Marsset, M.; Vernazza, P.; Gourgeot, F.; Dumas, C.; Birlan, M.; Lamy, P.; Binzel, R. P.

    2014-07-01

    We present 17 reflectance spectra of 12 high albedo (pv>0.14) Trojans (8 objects) and Hildas (4 objects) obtained with the ESO/VLT Echelle spectrograph X-SHOOTER in the 0.3-2.2um spectral range (14 spectra) and with the NASA/IRTF spectrograph SpeX in the 0.8-2.5um spectral range (3 spectra). X-SHOOTER spectra were normalized to unity at 0.55um and SpeX spectra were normalized to unity at 2.2um . The spectra presented in this work were collected between April and December 2013. (18 data files).

  2. BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgV H unmutated chronic lymphocytic leukemia (CLL) cells.

    PubMed

    Guarini, Anna; Chiaretti, Sabina; Tavolaro, Simona; Maggio, Roberta; Peragine, Nadia; Citarella, Franca; Ricciardi, Maria Rosaria; Santangelo, Simona; Marinelli, Marilisa; De Propris, Maria Stefania; Messina, Monica; Mauro, Francesca Romana; Del Giudice, Ilaria; Foà, Robert

    2008-08-01

    Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. To investigate the association between clinicobiologic features and responsiveness of CLL cells to anti-IgM stimulation, we evaluated gene expression changes and modifications in cell-cycle distribution, proliferation, and apoptosis of IgV(H) mutated (M) and unmutated (UM) samples upon BCR cross-linking. Unsupervised analysis highlighted a different response profile to BCR stimulation between UM and M samples. Supervised analysis identified several genes modulated exclusively in the UM cases upon BCR cross-linking. Functional gene groups, including signal transduction, transcription, cell-cycle regulation, and cytoskeleton organization, were up-regulated upon stimulation in UM cases. Cell-cycle and proliferation analyses confirmed that IgM cross-linking induced a significant progression into the G(1) phase and a moderate increase of proliferative activity exclusively in UM patients. Moreover, we observed only a small reduction in the percentage of subG(0/1) cells, without changes in apoptosis, in UM cases; contrariwise, a significant increase of apoptotic levels was observed in stimulated cells from M cases. These results document that a differential genotypic and functional response to BCR ligation between IgV(H) M and UM cases is operational in CLL, indicating that response to antigenic stimulation plays a pivotal role in disease progression.

  3. Perinatal Autopsy Findings in a Case of De Novo Hypohidrotic Ectodermal Dysplasia.

    PubMed

    Chikkannaiah, Panduranga; Nagaraju, Smitha; Kangle, Rajit; Gosavi, Mansi

    2015-01-01

    Ectodermal dysplasia are group of inherited disorders involving the developmental defects of ectodermal structures like hair, teeth, nails, sweat glands, and others. X-linked recessive inheritance is most common. Here we describe perinatal autopsy findings in a case of de novo ectodermal dysplasia in a female fetus. To the best of our knowledge, this is the first fetal autopsy description in a case of ectodermal dysplasia.

  4. Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation--a 5 year follow up.

    PubMed

    Schinwelski, M; Kierdaszuk, B; Dulski, J; Tońska, K; Kodroń, A; Sitek, E J; Bartnik, E; Kamińska, A; Kwieciński, H; Sławek, J

    2015-08-01

    Mutations in NADH dehydrogenase (ND) subunits of complex I lead to mitochondrial encephalomyopathies associated with various phenotypes. This report aims to present the patient's clinical symptomatology in the context of a very rare 13042G>A de novo mutation and with an emphasis on changing phenotypic expression and pronounced, long-standing response to levetiracetam.

  5. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

    NASA Astrophysics Data System (ADS)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  6. Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration[S

    PubMed Central

    Chen, Hui; Tran, Julie-Thu A.; Eckerd, Annette; Huynh, Tuan-Phat; Elliott, Michael H.; Brush, Richard S.; Mandal, Nawajes A.

    2013-01-01

    Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases in ceramide mediate photoreceptor apoptosis in LIRD and if inhibition of ceramide synthesis protects the retina. Sprague-Dawley rats were exposed to 2,700 lux white light for 6 h, and the retinal levels of ceramide and its intermediary metabolites were measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes of the de novo biosynthetic and sphingomyelinase pathways of ceramide generation were assayed, and gene expression was measured. The dosage and temporal effect of the ceramide synthase inhibitor FTY720 on the LIRD retina were measured by histological and functional analyses. Retinal ceramide levels increased coincident with the increase of dihydroceramide at various time points after light stress. Light stress in retina induces ceramide generation predominantly through the de novo pathway, which was prevented by systemic administration of FTY720 (10 mg/kg) leading to the protection of retinal structure and function. The neuroprotection of FTY720 was independent of its immunosuppressive action. We conclude that ceramide increase by de novo biosynthesis mediates photoreceptor apoptosis in the LIRD model and that inhibition of ceramide production protects the retina against light stress. PMID:23468130

  7. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

    PubMed

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  8. Everolimus immunosuppression for renal protection, reduction of allograft vasculopathy and prevention of allograft rejection in de-novo heart transplant recipients: could we have it all?

    PubMed

    Gude, Einar; Gullestad, Lars; Andreassen, Arne K

    2017-06-01

    De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction. The SCHEDULE trial compared de-novo Eve with significantly reduced CNI exposure and conversion to CNI-free treatment week 7-11 postheart transplant, with standard CNI immunosuppression. Improved renal function and attenuation of CAV was found among Eve patients, with higher numbers of treated acute rejections observed. With sustained superior renal and CAV related data also after 36 months with the Eve protocol, cardiac function was equally well preserved in both groups. According to the International Society of Heart and Lunge Transplantation registry, mammalian target of rapamycin inhibitor treatment is uncommon during the first postoperative year, with a prevalence of 20% in patients after 5 years. Current evidence suggests a greater benefit from these immunosuppressives if introduced at an earlier timepoint. Immunosuppressive protocols based on Eve treatment in de-novo patients should be further investigated and developed, enabling CNI avoidance before accelerating side-effects lead to irreversible damage.

  9. Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients.

    PubMed

    Yuan, Yongsheng; Tong, Qing; Zhang, Li; Jiang, Siming; Zhou, Hong; Zhang, Rui; Zhang, Shu; Xu, Qinrong; Li, Daqian; Zhou, Xiaobin; Ding, Jian; Zhang, Kezhong

    2016-01-01

    This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

  10. Donor-transmitted, donor-derived, and de novo cancer after liver transplant.

    PubMed

    Chapman, Jeremy R; Lynch, Stephen V

    2014-03-01

    Cancer is the third most common cause of death (after cardiovascular disease and infection) for patients who have a functioning kidney allograft. Kidney and liver transplant recipients have similar cancer risks because of immunosuppression but different risks because of differences in primary diseases that cause renal and hepatic failure and the inherent behavior of cancers in the liver. There are 4 types of cancer that may develop in liver allograft recipients: (1) recurrent cancer, (2) donor-transmitted cancer, (3) donor-derived cancer, and (4) de novo cancer. Identification of potential donor cancer transmission may occur at postmortem examination of a deceased donor or when a probable donor-transmitted cancer is identified in another recipient. Donor-transmitted cancer after liver transplant is rare in Australia, the United Kingdom, and the United States. Aging of the donor pool may increase the risk of subclinical cancer in donors. Liver transplant recipients have a greater risk of de novo cancer than the general population, and risk factors for de novo cancer in liver transplant recipients include primary sclerosing cholangitis, alcoholic liver disease, smoking, and increased age. Liver transplant recipients may benefit from cancer screening because they have a high risk, are clearly identifiable, and are under continuous medical supervision.

  11. De novo assembly of the transcriptome of the non-model plant Streptocarpus rexii employing a novel heuristic to recover locus-specific transcript clusters.

    PubMed

    Chiara, Matteo; Horner, David S; Spada, Alberto

    2013-01-01

    De novo transcriptome characterization from Next Generation Sequencing data has become an important approach in the study of non-model plants. Despite notable advances in the assembly of short reads, the clustering of transcripts into unigene-like (locus-specific) clusters remains a somewhat neglected subject. Indeed, closely related paralogous transcripts are often merged into single clusters by current approaches. Here, a novel heuristic method for locus-specific clustering is compared to that implemented in the de novo assembler Oases, using the same initial transcript collections, derived from Arabidopsis thaliana and the developmental model Streptocarpus rexii. We show that the proposed approach improves cluster specificity in the A. thaliana dataset for which the reference genome is available. Furthermore, for the S. rexii data our filtered transcript collection matches a larger number of distinct annotated loci in reference genomes than the Oases set, while containing a reduced overall number of loci. A detailed discussion of advantages and limitations of our approach in processing de novo transcriptome reconstructions is presented. The proposed method should be widely applicable to other organisms, irrespective of the transcript assembly method employed. The S. rexii transcriptome is available as a sophisticated and augmented publicly available online database.

  12. Exacerbation of liver steatosis following exposure to famine and overnutrition.

    PubMed

    Ning, Zhiyuan; Zhang, Kun; Zhao, Li; Lu, You; Sun, Honglin; Chen, Chi; Nie, Xiaomin; Lu, Meng; Wang, Ningjian; Lu, Yingli

    2017-10-01

    People suffering from famine in early life and overnutrition in adulthood may have an increased risk for liver steatosis. We aimed to investigate the effects and mechanisms of early nutrition restriction and overnutrition on de novo lipogenesis in the liver. Three-wk-old male rats were food restricted for 4 wk and refed a high-fat or normal fat diet individually in metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid synthetase expression was measured to estimate de novo lipogenesis in the liver. Parameters of glucose and lipid metabolism were measured with isotope assays. All four groups had comparable body weights. However, the famine high-fat diet group had the highest degree of liver steatosis, the greatest body fat ratio, and insulin resistance. Lipid accumulation, fatty acid synthetase expression, and gluconeogenesis in the liver were significantly higher in the famine and high-fat diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle glucose uptake. Under famine and high-fat refeeding stress, rats were extremely susceptible to developing hepatic steatosis. This is presumably a consequence of upregulation of de novo lipogenesis and enhanced glucose flux from muscle to de novo lipogenesis in the liver. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Importance of chlorine speciation on de novo formation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.

    PubMed

    Wikström, Evalena; Ryan, Shawn; Touati, Abderrahmane; Telfer, Marnie; Tabor, Dennis; Gullett, Brian K

    2003-03-15

    The role of chlorine speciation on de novo formation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/Fs) has been studied thoroughly in an entrained flow reactor during simulated waste combustion. The effects of gas-phase chlorine species such as chlorine (Cl2), hydrogen chloride (HCl), and chlorine radicals (Cl*), as well as ash-bound chlorine, on PCDD/F de novo formation were isolated for investigation. The ash-bound chlorine alone was observed to be a sufficient chlorine source for PCDD/F formation. The addition of HCl to the system did not influence the yields of the PCDDs/Fs nor the degree of chlorination due to its poor chlorinating ability. Addition of 200 ppm of Cl2 to the ash-feed system resulted in increased PCDD/F yields, especially for the octa- and hepta-chlorinated congeners. Altering the reaction temperature to enable the presence of only Cl2 to the system did not change the yields of PCDD/F compared to those when both Cl2/Cl* were present. However, comparison between ash-bound and gas-phase chlorine, the latter at a concentration typical of a realistic combustion process, revealed ash-bound chlorine to be the more important chlorine source for de novo formation of PCDD/F in a full-scale incinerator.

  14. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    PubMed Central

    Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

    2012-01-01

    Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

  15. Surgically treated de novo cervico-medullary arachnoid cyst in a symptomatic adult patient.

    PubMed

    Clifton, William; Rahmathulla, Gazanfar; Tavanaiepour, Kourosh; Alcindor, Dunbar; Jakubek, George; Tavanaiepour, Daryoush

    2018-05-16

    Arachnoid cysts are a relatively common finding in adult patients, especially with the advent of advanced imaging techniques. The overall incidence ranges from 1-2%, and the majority are clinically silent 1,2 . Arachnoid cysts are postulated to arise by congenital anomalies or trauma 1 . De novo formation of arachnoid cysts has been reported, but is exceptionally rare and mostly found in the pediatric population after head trauma 3-5 . There have only been two reported cases of symptomatic de novo arachnoid cyst formation in adult patients to date, both with histories of head trauma 6,7 . We present a case of a 71-year-old male patient with progressive vertigo who had previous brain MRI studies without abnormalities. Another MRI was performed three years from the last study that showed interval development of a large cystic lesion compressing the right cervicomedullary junction, as well as radiologic evidence of neurosarcoidosis. Intraoperative findings showed a cystic mass with clear, gelatinous fluid. The cyst was drained and the walls were resected and sent to pathology. Histopathologic testing confirmed the lesion was an arachnoid cyst. The patient's vertiginous symptoms improved after surgery. This case represents the first incidence of a pathology proven, non-traumatic de novo arachnoid cyst. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. De novo point mutations in patients diagnosed with ataxic cerebral palsy.

    PubMed

    Parolin Schnekenberg, Ricardo; Perkins, Emma M; Miller, Jack W; Davies, Wayne I L; D'Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O'Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis; Jackson, Mandy; Tucker, Stephen J; Németh, Andrea H

    2015-07-01

    Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  17. De novo GTP Biosynthesis Is Critical for Virulence of the Fungal Pathogen Cryptococcus neoformans

    PubMed Central

    Morrow, Carl A.; Valkov, Eugene; Stamp, Anna; Chow, Eve W. L.; Lee, I. Russel; Wronski, Ania; Williams, Simon J.; Hill, Justine M.; Djordjevic, Julianne T.; Kappler, Ulrike; Kobe, Bostjan; Fraser, James A.

    2012-01-01

    We have investigated the potential of the GTP synthesis pathways as chemotherapeutic targets in the human pathogen Cryptococcus neoformans, a common cause of fatal fungal meningoencephalitis. We find that de novo GTP biosynthesis, but not the alternate salvage pathway, is critical to cryptococcal dissemination and survival in vivo. Loss of inosine monophosphate dehydrogenase (IMPDH) in the de novo pathway results in slow growth and virulence factor defects, while loss of the cognate phosphoribosyltransferase in the salvage pathway yielded no phenotypes. Further, the Cryptococcus species complex displays variable sensitivity to the IMPDH inhibitor mycophenolic acid, and we uncover a rare drug-resistant subtype of C. gattii that suggests an adaptive response to microbial IMPDH inhibitors in its environmental niche. We report the structural and functional characterization of IMPDH from Cryptococcus, revealing insights into the basis for drug resistance and suggesting strategies for the development of fungal-specific inhibitors. The crystal structure reveals the position of the IMPDH moveable flap and catalytic arginine in the open conformation for the first time, plus unique, exploitable differences in the highly conserved active site. Treatment with mycophenolic acid led to significantly increased survival times in a nematode model, validating de novo GTP biosynthesis as an antifungal target in Cryptococcus. PMID:23071437

  18. A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

    PubMed

    Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

    2015-09-01

    Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

  19. "Uh" and "Um" Revisited: Are They Interjections for Signaling Delay?

    ERIC Educational Resources Information Center

    O'Connell, Daniel C.; Kowal, Sabine

    2005-01-01

    Clark and Fox Tree (2002) have presented empirical evidence, based primarily on the London-Lund corpus (LL; Svartvik & Quirk, 1980), that the fillers "uh" and "um" are conventional English words that signal a speaker's intention to initiate a minor and a major delay, respectively. We present here empirical analyses of "uh" and "um" and of silent…

  20. The attitudes, role & knowledge of mental health nurses towards euthanasia because of unbearable mental suffering in Belgium: a pilot study.

    PubMed

    Demedts, Dennis; Roelands, Marc; Libbrecht, Julien; Bilsen, Johan

    2018-05-26

    Euthanasia because of unbearable mental suffering (UMS euthanasia) has been legal in Belgium since 2002, under certain circumstances that govern careful practice. Despite the legal framework, there are specific difficulties and concerns regarding UMS euthanasia. Mental health nurses are often involved in the process, but little is known about their attitudes towards UMS euthanasia, their role and their knowledge. To determine the attitudes, role and knowledge of mental health nurses regarding UMS euthanasia. A cross-sectional survey was performed at a convenience sample of four psychiatric hospitals in Belgium (n=133) as a pilot study. Self-administered questionnaires were provided to mental health nurses. Half the nurses in our sample had been involved at least once in the process of UMS euthanasia. A large majority of mental health nurses were supportive of UMS euthanasia. Nurses show differences in attitudes related to the different psychiatric pathologies of the patients, and in whether or not minors are involved. In some cases, they believed that the mental suffering of psychiatric patients can be unbearable and irreversible and that psychiatric patients can be competent to voluntarily request UMS euthanasia. Nurses stated that they have an important role in the UMS euthanasia process, but also demanded more knowledge and clear guidelines to implement the procedure. Nurses have a key role regarding UMS euthanasia but face several challenges: the recent process, resistance to a multidisciplinary approach by psychiatrists and an unclear role defined by the legal framework. Nurses do not appear to have a common voice on the topic and the development of clear guidelines appears to be essential. Social recovery can offer a way out of an UMS euthanasia request, but it will not always offer a solution. Sufficient attention must be paid to how mental health nurses can be involved in the process of UMS euthanasia at various levels: bedside practice, healthcare management, education and policy. A form of systematic cooperation between nurses, physicians and patients can contribute to the utmost careful decision-making process needed in these cases. There is a need for proper training in: knowledge of psychiatric pathologies and remaining treatment options; communication skills; the legal framework and all its difficulties; transdisciplinary and multicultural approaches; ethical reflection and how nurses handle their own emotions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. The short form of the recombinant CAL-A-type lipase UM03410 from the smut fungus Ustilago maydis exhibits an inherent trans-fatty acid selectivity.

    PubMed

    Brundiek, Henrike; Saß, Stefan; Evitt, Andrew; Kourist, Robert; Bornscheuer, Uwe T

    2012-04-01

    The Ustilago maydis lipase UM03410 belongs to the mostly unexplored Candida antarctica lipase (CAL-A) subfamily. The two lipases with [corrected] the highest identity are a lipase from Sporisorium reilianum and the prototypic CAL-A. In contrast to the other CAL-A-type lipases, this hypothetical U. maydis lipase is annotated to possess a prolonged N-terminus of unknown function. Here, we show for the first time the recombinant expression of two versions of lipase UM03410: the full-length form (lipUMf) and an Nterminally truncated form (lipUMs). For comparison to the prototype, the expression of recombinant CAL-A in E. coli was investigated. Although both forms of lipase UM03410 could be expressed functionally in E. coli, the N-terminally truncated form (lipUMs) demonstrated significantly higher activities towards p-nitrophenyl esters. The functional expression of the N-terminally truncated lipase was further optimized by the appropriate choice of the E. coli strain, lowering the cultivation temperature to 20 °C and enrichment of the cultivation medium with glucose. Primary characteristics of the recombinant lipase are its pH optimum in the range of 6.5-7.0 and its temperature optimum at 55 °C. As is typical for lipases, lipUM03410 shows preference for long chain fatty acid esters with myristic acid ester (C14:0 ester) being the most preferred one.More importantly, lipUMs exhibits an inherent preference for C18:1Δ9 trans and C18:1Δ11 trans-fatty acid esters similar to CAL-A. Therefore, the short form of this U. maydis lipase is the only other currently known lipase with a distinct trans-fatty acid selectivity.

  2. Uh and um revisited: are they interjections for signaling delay?

    PubMed

    O'Connell, Daniel C; Kowal, Sabine

    2005-11-01

    Clark and Fox Tree (2002) have presented empirical evidence, based primarily on the London-Lund corpus (LL; Svartvik & Quirk, 1980), that the fillers uh and um are conventional English words that signal a speaker's intention to initiate a minor and a major delay, respectively. We present here empirical analyses of uh and um and of silent pauses (delays) immediately following them in six media interviews of Hillary Clinton. Our evidence indicates that uh and um cannot serve as signals of upcoming delay, let alone signal it differentially: In most cases, both uh and um were not followed by a silent pause, that is, there was no delay at all; the silent pauses that did occur after um were too short to be counted as major delays; finally, the distributions of durations of silent pauses after uh and um were almost entirely overlapping and could therefore not have served as reliable predictors for a listener. The discrepancies between Clark and Fox Tree's findings and ours are largely a consequence of the fact that their LL analyses reflect the perceptions of professional coders, whereas our data were analyzed by means of acoustic measurements with the PRAAT software (www.praat.org). A comparison of our findings with those of O'Connell, Kowal, and Ageneau (2005) did not corroborate the hypothesis of Clark and Fox Tree that uh and um are interjections: Fillers occurred typically in initial, interjections in medial positions; fillers did not constitute an integral turn by themselves, whereas interjections did; fillers never initiated cited speech, whereas interjections did; and fillers did not signal emotion, whereas interjections did. Clark and Fox Tree's analyses were embedded within a theory of ideal delivery that we find inappropriate for the explication of these phenomena.

  3. Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: A randomized clinical trial.

    PubMed

    González-Sarrías, Antonio; García-Villalba, Rocío; Romo-Vaquero, María; Alasalvar, Cesarettin; Örem, Asim; Zafrilla, Pilar; Tomás-Barberán, Francisco A; Selma, María V; Espín, Juan Carlos

    2017-05-01

    The pomegranate lipid-lowering properties remain controversial, probably due to the interindividual variability in polyphenol (ellagitannins) metabolism. We aimed at investigating whether the microbially derived ellagitannin-metabolizing phenotypes, i.e. urolithin metabotypes A, (UM-A), B (UM-B), and 0 (UM-0), influence the effects of pomegranate extract (PE) consumption on 18 cardiovascular risk biomarkers in healthy overweight-obese individuals. A double-blind, crossover, dose-response, randomized, placebo-controlled trial was conducted. The study (POMEcardio) consisted of two test phases (dose-1 and dose-2, lasting 3 weeks each) and a 3-week washout period between each phase. Forty-nine participants (BMI > 27 kg/m 2 ) daily consumed one (dose-1, 160 mg phenolics/day) or four (dose-2, 640 mg phenolics/day) PE or placebo capsules. Notably, UM-B individuals showed the highest baseline cardiovascular risk. After dose-2, total cholesterol (-15.5 ± 3.7%), LDL-cholesterol (-14.9 ± 2.1%), small LDL-cholesterol (-47 ± 7%), non-HDL-cholesterol (-11.3 ± 2.5%), apolipoprotein-B (-12 ± 2.2%), and oxidized LDL-cholesterol -24 ± 2.5%) dose dependently decreased (P < 0.05) but only in UM-B subjects. These effects were partially correlated with urolithin production and the increase in Gordonibacter levels. Three (50%) nonproducers (UM-0) became producers following PE consumption. UM clustering suggests a personalized effect of ellagitannin-containing foods and could explain the controversial pomegranate benefits. Research on the specific role of urolithins and the microbiota associated with each UM is warranted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Medical condition and care of undocumented migrants in ambulatory clinics in Tel Aviv, Israel: assessing unmet needs.

    PubMed

    Mor, Zohar; Raveh, Yuval; Lurie, Ido; Leventhal, Alex; Gamzu, Roni; Davidovitch, Nadav; Benari, Orel; Grotto, Itamar

    2017-07-14

    Approximately 150,000 undocumented migrants (UM) who are medically uninsured reside in Israel, including ~50,000 originating from the horn of Africa (MHA). Free medical-care is provided by two walk-in clinics in Tel-Aviv. This study aims to compare the medical complaints of UM from different origins, define their community health needs and assess gaps between medical needs and available services. This cross-sectional study included a random sample of 610 UM aged 18-64 years, who were treated in these community clinics between 2008 and 2011. The study compared UM who had complex medical conditions which necessitated referral to more equipped medical settings with UM having mild/simple medical conditions, who were treated at the clinics. MHA were younger, unemployed and more commonly males compared with UM originating from other countries. MHA also had longer referral-delays and visited the clinics less frequently. UM with complex medical conditions were more commonly females, had chronic diseases and demonstrated longer referral-delays than those who had mild/simple medical conditions. The latter more commonly presented with complained of respiratory, muscular and skeletal discomfort. In multivariate analysis, the variables which predicted complex medical conditions included female gender, chronic illnes and self-referral to the clinics. The ambulatory clinics were capable of responding to mild/simple medical conditions. Yet, the health needs of women and migrants suffering from complex medical conditions and chronic diseases necessitated referrals to secondary/tertiary medical settings, while jeopardizing the continuity of care. The health gaps can be addressed by a more holistic social approach, which includes integration of UM in universal health insurance.

  5. Particulate matter and polycyclic aromatic hydrocarbons from forest fires: impacts on air quality and occupational risks assessment

    NASA Astrophysics Data System (ADS)

    Oliveira, Marta Madalena Marques de

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  6. Reciprocal interaction between human microvascular endothelial cells and mesenchymal stem cells on macroporous granules of nanostructured-hydroxyapatite agglomerates

    NASA Astrophysics Data System (ADS)

    Laranjeira, Marta de Sousa

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  7. Analysis of vegetation dynamics using time-series vegetation index data from Earth observation satellites

    NASA Astrophysics Data System (ADS)

    Rodrigues, Arlete da Silva

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  8. Biological effects of polyacrylic acid-coated and non-coated superparamagnetic iron oxide nanoparticles in in vitro and in vivo experimental models

    NASA Astrophysics Data System (ADS)

    Couto, Diana Manuel Mocho de Bastos

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  9. Impact evaluation of the large scale integration of electric vehicles in the security of supply

    NASA Astrophysics Data System (ADS)

    Bremermann, Leonardo Elizeire

    As piroxenas sao um vasto grupo de silicatos minerais encontrados em muitas rochas igneas e metamorficas. Na sua forma mais simples, estes silicatos sao constituidas por cadeias de SiO3 ligando grupos tetrahedricos de SiO4. A formula quimica geral das piroxenas e M2M1T2O6, onde M2 se refere a catioes geralmente em uma coordenacao octaedrica distorcida (Mg2+, Fe2+, Mn2+, Li+, Ca2+, Na+), M1 refere-se a catioes numa coordenacao octaedrica regular (Al3+, Fe3+, Ti4+, Cr3+, V3+, Ti3+, Zr4+, Sc3+, Zn2+, Mg2+, Fe2+, Mn2+), e T a catioes em coordenacao tetrahedrica (Si4+, Al3+, Fe3+). As piroxenas com estrutura monoclinica sao designadas de clinopiroxenes. A estabilidade das clinopyroxenes num espectro de composicoes quimicas amplo, em conjugacao com a possibilidade de ajustar as suas propriedades fisicas e quimicas e a durabilidade quimica, tem gerado um interesse mundial devido a suas aplicacoes em ciencia e tecnologia de materiais. Este trabalho trata do desenvolvimento de vidros e de vitro-cerâmicos baseadas de clinopiroxenas para aplicacoes funcionais. O estudo teve objectivos cientificos e tecnologicos; nomeadamente, adquirir conhecimentos fundamentais sobre a formacao de fases cristalinas e solucoes solidas em determinados sistemas vitro-cerâmicos, e avaliar a viabilidade de aplicacao dos novos materiais em diferentes areas tecnologicas, com especial enfase sobre a selagem em celulas de combustivel de oxido solido (SOFC). Com este intuito, prepararam-se varios vidros e materiais vitro-cerâmicos ao longo das juntas Enstatite (MgSiO3) - diopsidio (CaMgSi2O6) e diopsidio (CaMgSi2O6) - Ca - Tschermak (CaAlSi2O6), os quais foram caracterizados atraves de um vasto leque de tecnicas. Todos os vidros foram preparados por fusao-arrefecimento enquanto os vitro-cerâmicos foram obtidos quer por sinterizacao e cristalizacao de fritas, quer por nucleacao e cristalizacao de vidros monoliticos. Estudaram-se ainda os efeitos de varias substituicoes ionicas em composicoes de diopsidio contendo Al na estrutura, sinterizacao e no comportamento durante a cristalizacao de vidros e nas propriedades dos materiais vitro-cerâmicos, com relevância para a sua aplicacao como selantes em SOFC. Verificou-se que Foi observado que os vidros/vitro-cerâmicos a base de enstatite nao apresentavam as caracteristicas necessarias para serem usados como materiais selantes em SOFC, enquanto as melhores propriedades apresentadas pelos vitro-cerâmicos a base de diopsidio qualificaram-nos para futuros estudos neste tipo de aplicacoes. Para alem de investigar a adequacao dos vitro-cerâmicos a base de clinopyroxene como selantes, esta tese tem tambem como objetivo estudar a influencia dos agentes de nucleacao na nucleacao em volume dos vitro-cerâmicos resultantes a base de diopsidio, de modo a qualifica-los como potenciais materiais hopedeiros de residuos nucleares radioactivos.

  10. High-speed, large-area, p-i-n InGaAs photodiode linear array at 2-micron wavelength

    NASA Astrophysics Data System (ADS)

    Joshi, Abhay; Datta, Shubhashish

    2012-06-01

    We present 16-element and 32-element lattice-mismatched InGaAs photodiode arrays having a cut-off wavelength of ~2.2 um. Each 100 um × 200 um large pixel of the 32-element array has a capacitance of 2.5 pF at 5 V reverse bias, thereby allowing a RC-limited bandwidth of ~1.3 GHz. At room temperature, each pixel demonstrates a dark current of 25 uA at 5 V reverse bias. Corresponding results for the 16-element array having 200 um × 200 um pixels are also reported. Cooling the photodiode array to 150K is expected to reduce its dark current to < 50 nA per pixel at 5 V reverse bias. Additionally, measurement results of 2-micron single photodiodes having 16 GHz bandwidth and corresponding PIN-TIA photoreceiver having 6 GHz bandwidth are also reported.

  11. Development of a non-contextual model for determining the autonomy level of intelligent unmanned systems

    NASA Astrophysics Data System (ADS)

    Durst, Phillip J.; Gray, Wendell; Trentini, Michael

    2013-05-01

    A simple, quantitative measure for encapsulating the autonomous capabilities of unmanned systems (UMS) has yet to be established. Current models for measuring a UMS's autonomy level require extensive, operational level testing, and provide a means for assessing the autonomy level for a specific mission/task and operational environment. A more elegant technique for quantifying autonomy using component level testing of the robot platform alone, outside of mission and environment contexts, is desirable. Using a high level framework for UMS architectures, such a model for determining a level of autonomy has been developed. The model uses a combination of developmental and component level testing for each aspect of the UMS architecture to define a non-contextual autonomous potential (NCAP). The NCAP provides an autonomy level, ranging from fully non- autonomous to fully autonomous, in the form of a single numeric parameter describing the UMS's performance capabilities when operating at that level of autonomy.

  12. Unique response of lung acetyl-CoA carboxylase to inhibitors

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

    Patterson, C.E.; Davis, K.S.; Rhoades, R.A.

    1986-05-01

    Fatty acid synthesis (FAS) in lung is not inhibited by c-AMP analogs or aminophylline although these agents inhibit FAS in other lipogenic tissues. To further characterize FAS in lung, the authors examined the response of cultured fetal lung explants to known inhibitors of FAS in liver: t-butyl benzoic acid (tBB-which binds CoA and inhibits acetyl-CoA carboxylase) and palmitate (an allosteric effector of acetyl-CoA carboxylase). Explants derived from d18 fetuses (term=22d) were cultured 2d in F12k media containing 10mM lactate, 2mM glucose, and 10mM Hepes. At 48h, FAS was determined by incubation with /sup 3/H/sub 2/O (control = 3892 +/- 755more » nmoles C2 units/g/h) and surfactant lipid production estimated by incorporation of /sup 14/C-choline into DSPC (control = 35.8 +/- 9.0 nmoles/g/h). Addition of tBB (50uM) did not significantly alter FAS or choline incorporation. Addition of palmitate (0.15mM) in either ethanol (1% final conc.) or albumin (3% final conc.) did not result in diminished FAS. Palmitate did increase DSPC labeling 20%, indicating that in these cultures the rate of surfactant synthesis is partially dependent upon palmitate availability. These data show that lung is unique in its unresponsiveness to various inhibitors of FAS which act at the level acetyl-CoA carboxylase and suggest that FAS is maintained in order to insure a de novo palmitate supply for surfactant lipid synthesis.« less

  13. Targeting the HER family with Pan-HER effectively overcomes resistance to cetuximab

    PubMed Central

    Iida, Mari; Bahrar, Harsh; Brand, Toni M; Pearson, Hannah E; Coan, John P; Orbuch, Rachel A; Flanigan, Bailey G; Swick, Adam D; Prabakaran, Prashanth; Lantto, Johan; Horak, Ivan D.; Kragh, Michael; Salgia, Ravi; Kimple, Randy J; Wheeler, Deric L

    2016-01-01

    Cetuximab, an antibody against the Epidermal Growth Factor Receptor (EGFR) has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do initially respond become refractory, highlighting both intrinsic and acquired resistance to cetuximab as significant clinical problems. To understand mechanistically how cancerous cells acquire resistance, we previously developed models of acquired resistance using the H226 NSCLC and UM-SCC1 HNSCC cell lines. Cetuximab-resistant clones showed a robust upregulation and dependency on the HER family receptors EGFR, HER2 and HER3. Here, we examined Pan-HER, a mixture of six antibodies targeting these receptors on cetuximab-resistant clones. In cells exhibiting acquired or intrinsic resistance to cetuximab, Pan-HER treatment decreased all three receptors’ protein levels and down-stream activation of AKT and MAPK. This correlated with decreased cell proliferation in cetuximab-resistant clones. To determine whether Pan-HER had a therapeutic benefit in vivo, we established de novo cetuximab-resistant mouse xenografts and treated resistant tumors with Pan-HER. This regimen resulted in a superior growth delay of cetuximab-resistant xenografts compared to mice continued on cetuximab. Furthermore, intrinsically cetuximab-resistant HNSCC patient-derived xenograft tumors treated with Pan-HER exhibited significant growth delay compared to vehicle/cetuximab controls. These results suggest that targeting HER family receptors simultaneously with Pan-HER is a promising treatment strategy for tumors displaying intrinsic or acquired resistance to cetuximab. PMID:27422810

  14. REDUCTIVE DEHALOGENATION OF HEXACHLOROETHANE, CARBON TETRACHLORIDE, AND BROMOFORM BY ANAHYDROQUINONE DISULFONATE AND HUMIC ACID

    EPA Science Inventory

    The reductive dehalogenation of hexachloroethane (C2CI6), carbon tetrachloride (CC14), and bromoform (CHBr3) was examined at 50 degrees C in aqueous solutions containing either (1) 500 uM of 2,6-anthrahydroquinone disulfonate (AHQDS), (2) 250 uM Fe2+, or (3) 250 uM HS. The pH ran...

  15. Assessment of Teams and Teamwork in the University of Maryland Libraries

    ERIC Educational Resources Information Center

    Baughman, M. Sue

    2008-01-01

    Teams play an important role in the University of Maryland (UM) Libraries. Since 1998, teams and collaborative teamwork have become the way librarians address the myriad of issues affecting the needs of UM's faculty, students, and staff. There has been much change in the UM Libraries over the past nine years, and the development is ongoing.…

  16. Somatic embryogenesis in immature cotyledons of Manchurian ash (Fraxinus mandshurica Rupr.)

    USDA-ARS?s Scientific Manuscript database

    Somatic embryogenesis was obtained from immature cotyledon explants that were cultured on half-strength Murashige and Skoog (MS) salts and vitamins with 5.4 uM naphthaleneacetic acid (NAA) and 0.2 uM thidiazuron (TDZ) plus a 4x4 factorial combination of 0,9.8, 34.6, or 49.2 uM indole-3-butyric acid ...

  17. VizieR Online Data Catalog: Young clumps embedded in IRDC (Traficante+, 2015)

    NASA Astrophysics Data System (ADS)

    Traficante, A.; Fuller, G. A.; Peretto, N.; Pineda, J. E.; Molinari, S.

    2015-06-01

    Photometric parameters for 667 starless clumps (sources identified at 160um with a counterpart at 250 and 350um) and 1056 protostellar clumps (sources identified at 160um with a counterpart at 70, 250 and 350um). Photometric parameters obtained with Hyper photometry code (2015A&A...574A.119T). The photometry is corrected for aperture and colour corrections. The parameter list is the standard Hyper output (see description below). SED fit parameters for 650 starless clumps and 1034 protostellar clumps (all clumps with good SED fitting: Chi2<10, Temperature<40K. See the paper for details) (4 data files).

  18. VizieR Online Data Catalog: Draco nebula Herschel 250um map (Miville-Deschenes+, 2017)

    NASA Astrophysics Data System (ADS)

    Miville-Deschenes, M.-A.; Salome, Q.; Martin, P. G.; Joncas, G.; Blagrave, K.; Dassas, K.; Abergel, A.; Beelen, A.; Boulanger, F.; Lagache, G.; Lockman, F. J.; Marshall, D. J.

    2017-03-01

    Draco was observed with Herschel PACS (110 and 170um) and SPIRE (250, 350 and 500um) as part of the open-time program "First steps toward star formation: unveiling the atomic to molecular transition in the diffuse interstellar medium" (P.I. M-A Miville-Deschenes). A field of 3.85x3.85 was observed in parallel mode. Unfortunately, an error occurred during the acquisition of the PACS data making them unusable. Therefore, the results presented here are solely based on SPIRE data, especially the 250um map that has the highest angular resolution. (2 data files).

  19. High Frequency GaAs Bulk Acousto-Optic Devices For Modulators And Frequency Shifters At 1.3um And 1.5um In Fiber-Optics

    NASA Astrophysics Data System (ADS)

    Soos, J. I.; Rosemeier, R. G.

    1989-02-01

    The edge of a transmission window for a GaAs Bragg cell starts about lum, which allows this material to be used for infrared fiber-optic applications, especially at 1.3um and 1.5um. The single crystal of GaAs is acoustically anisotropic and has the highest figure of merit, M2, along <111> direction for a longitudinal mode sound wave. Recently, Brimrose has designed and fabricated an acousto-optic modulator from GaAs operating at a carrier frequency of 2.3 GHz with a diffraction efficiency of 4%/RF watt.

  20. VizieR Online Data Catalog: LRLL54361 protostar Herschel/PACS fluxes (Balog+, 2014)

    NASA Astrophysics Data System (ADS)

    Balog, Z.; Muzerolle, J.; Flaherty, K.; Detre, O. H.; Bouwmann, J.; Furlan, E.; Gutermuth, R.; Juhasz, A.; Bally, J.; Nielbock, M.; Klaas, U.; Krause, O.; Henning, T.; Marton, G.

    2017-03-01

    We observed a 14'x14' area in IC348 with the Photodetector Array Camera and Spectrometer (PACS; Poglitsch et al. 2010A&A...518L...2P) Herschel Space Observatory (Pilbratt et al. 2010A&A...518L...1P) simultaneously at 70 and 160um 24 times in scan map mode. An additional five epoch were observed during a later pulse phase of LRLL54361 in all three PACS photometer bands. The PACS spectrograph consists of a 5x5 array of 9.4" x 9.4" spatial pixels (hereafter referred to as spaxels) covering the spectral range from 52-210 um with λ/δλ ~1000-3000. Spectra were obtained in two spectral orders simultaneously, with the second order ranging from 51 to 105um and the first order from 102 to 210um. The spatial resolution of PACS-S ranges from ~9'' at 50um to ~18'' at 210um. Our target was observed in the standard range-scan spectroscopy mode with a grating step size corresponding to Nyquist sampling (see further Poglitsch et al. 2010A&A...518L...2P). (1 data file).

  1. [Estimation of uncertainty of measurement in clinical biochemistry].

    PubMed

    Enea, Maria; Hristodorescu, Cristina; Schiriac, Corina; Morariu, Dana; Mutiu, Tr; Dumitriu, Irina; Gurzu, B

    2009-01-01

    The uncertainty of measurement (UM) or measurement uncertainty is known as the parameter associated with the result of a measurement. Repeated measurements usually reveal slightly different results for the same analyte, sometimes a little higher, sometimes a little lower, because the results of a measurement are depending not only by the analyte itself, but also, by a number of error factors that could give doubts about the estimate. The uncertainty of the measurement represent the quantitative, mathematically expression of this doubt. UM is a range of measured values which is probably to enclose the true value of the measured. Calculation of UM for all types of laboratories is regularized by the ISO Guide to the Expression of Uncertainty in Measurement (abbreviated GUM) and the SR ENV 13005 : 2003 (both recognized by European Accreditation). Even if the GUM rules about UM estimation are very strictly, the offering of the result together with UM will increase the confidence of customers (patients or physicians). In this study the authors are presenting the possibilities of UM assessing in labs from our country by using the data obtained in the procedures of methods validation, during the internal and external quality control.

  2. VizieR Online Data Catalog: Spectrophotometric distances of HII regions (Moises+, 2011)

    NASA Astrophysics Data System (ADS)

    Moises, A. P.; Damineli, A.; Figueredo, E.; Blum, R. D.; Conti, P. S.; Barbosa, C. L.

    2011-11-01

    The J-band (λ1.28um, δλ=0.3um), H-band (λ1.63um, δλ=0.3um) and Ks-band (λ2.19um, δλ=0.4um) images were obtained on the nights of 1999 May 1, 4 and 20, 2000 May 19 and 21 and 2001 July 10 and 12, at the Cerro Tololo Inter-American Observatory (CTIO) 4-m Blanco telescope, using the facility's infrared imager OSIRIS, which has a field of view (FOV) of 93x93arcsec2 and a pixel scale of 0.161arcsec/pixel. On the nights of 2005 Jult 3-6 and 11 and 2006 June 3-7, we obtained images using the facility's infrared imager ISPI (with a FOV of 10.25x10.25arcmin2 and a pixel scale of 0.3arcsec/pix), also at the 4-m Blanco telescope. Also, on the nights of 1998 August 28 and 29, we obtained images on the CTIO 4-m telescope using the facility's infrared imager CIRIM (with a FOV of 102x102arcsec2 and a pixel scale of 0.40arcsec/pix). (3 data files).

  3. Unconsummated marriage: can it still be considered a consequence of vaginismus?

    PubMed

    Michetti, P M; Silvaggi, M; Fabrizi, A; Tartaglia, N; Rossi, R; Simonelli, C

    2014-01-01

    Unconsummated marriage (UM) is the failure to perform successful sexual intercourse at the beginning of the marriage. Vaginismus has been traditionally reported as the leading cause. ED is also a leading cause for UM. This appears to be a significant problem in the conservative middle-Eastern societies and in the developing countries, where couples are strongly prevented by religious rules and cultural taboos from sexual experiences before wedding. One could think that according to major sexual freedom and information, in Western countries UM is now disappearing, but the number of observed cases by the authors in 2008-2012 was relevant. The aim of this study is to compare the literature data from non-Western countries with the features of UM in Western ones, focusing on cases observed by the authors, and to verify whether the etiology of UM proposed in the '70s is still relevant, outlining any changes that occur in current reality. In our series, traditional appearance of UM is no more effective, while the role of man is undervalued, because of his frailty, lack of self-confidence and ignorance, expressing a social and cultural change of man's role in the couple.

  4. Elucidating the role of the FoxO3a transcription factor in the IGF-1-induced migration and invasion of uveal melanoma cancer cells.

    PubMed

    Yan, Fengxia; Liao, Rifang; Farhan, Mohd; Wang, Tinghuai; Chen, Jiashu; Wang, Zhong; Little, Peter J; Zheng, Wenhua

    2016-12-01

    Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis. FoxO3a is a Forkhead box O (FOXO) transcription factor and a downstream target of the IGF-1R/PI3K/Akt pathway involved in a number of physiological and pathological processes including cancer. However, the role of FoxO3a in UM is unknown. In the present study, we investigated fundamental mechanisms in the growth, migration and invasion of UM and the involvement of FoxO3a. IGF-1 increased the cell viability, invasion, migration and S-G2/M cell cycle phase accumulation of UM cells. Western blot analysis showed that IGF-1 led to activation of Akt and concomitant phosphorylation of FoxO3a. FoxO3a phosphorylation was associated with its translocation into the cytoplasm from the nucleus and its functional inhibition led to the inhibition of expression of Bim and p27, but an increase in the expression of Cyclin D1. The effects of IGF-1 on UM cells were reversed by LY294002 (a PI3K inhibitor) or Akt siRNA, and the overexpression of FoxO3a also attenuated basal invasion and migration of UM. Taken all together, these results suggest that inhibition of FoxO3a by IGF-1 via the PI3K/Akt pathway has an important role in IGF-1 induced proliferation and invasion of UM cells. These findings also support FoxO3a and IGF signaling may represent a valid target for investigating the development of new strategies for the treatment and prevention of the pathology of UM. Copyright © 2016. Published by Elsevier Masson SAS.

  5. A new approach for annotation of transposable elements using small RNA mapping

    PubMed Central

    El Baidouri, Moaine; Kim, Kyung Do; Abernathy, Brian; Arikit, Siwaret; Maumus, Florian; Panaud, Olivier; Meyers, Blake C.; Jackson, Scott A.

    2015-01-01

    Transposable elements (TEs) are mobile genomic DNA sequences found in most organisms. They so densely populate the genomes of many eukaryotic species that they are often the major constituents. With the rapid generation of many plant genome sequencing projects over the past few decades, there is an urgent need for improved TE annotation as a prerequisite for genome-wide studies. Analogous to the use of RNA-seq for gene annotation, we propose a new method for de novo TE annotation that uses as a guide 24 nt-siRNAs that are a part of TE silencing pathways. We use this new approach, called TASR (for Transposon Annotation using Small RNAs), for de novo annotation of TEs in Arabidopsis, rice and soybean and demonstrate that this strategy can be successfully applied for de novo TE annotation in plants. Executable PERL is available for download from: http://tasr-pipeline.sourceforge.net/ PMID:25813049

  6. Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase.

    PubMed

    Lunev, Sergey; Bosch, Soraya S; Batista, Fernando A; Wang, Chao; Li, Jingyao; Linzke, Marleen; Kruithof, Paul; Chamoun, George; Dömling, Alexander S S; Wrenger, Carsten; Groves, Matthew R

    2018-03-11

    Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. T-IDBA: A de novo Iterative de Bruijn Graph Assembler for Transcriptome

    NASA Astrophysics Data System (ADS)

    Peng, Yu; Leung, Henry C. M.; Yiu, S. M.; Chin, Francis Y. L.

    RNA-seq data produced by next-generation sequencing technology is a useful tool for analyzing transcriptomes. However, existing de novo transcriptome assemblers do not fully utilize the properties of transcriptomes and may result in short contigs because of the splicing nature (shared exons) of the genes. We propose the T-IDBA algorithm to reconstruct expressed isoforms without reference genome. By using pair-end information to solve the problem of long repeats in different genes and branching in the same gene due to alternative splicing, the graph can be decomposed into small components, each corresponds to a gene. The most possible isoforms with sufficient support from the pair-end reads will be found heuristically. In practice, our de novo transcriptome assembler, T-IDBA, outperforms Abyss substantially in terms of sensitivity and precision for both simulated and real data. T-IDBA is available at http://www.cs.hku.hk/~alse/tidba/

  8. Partial De Novo Sequencing and Unusual CID Fragmentation of a 7 kDa, Disulfide-Bridged Toxin

    NASA Astrophysics Data System (ADS)

    Medzihradszky, Katalin F.; Bohlen, Christopher J.

    2012-05-01

    A 7 kDa toxin isolated from the venom of the Texas coral snake ( Micrurus tener tener) was subjected to collision-induced dissociation (CID) and electron-transfer dissociation (ETD) analyses both before and after reduction at low pH. Manual and automated approaches to de novo sequencing are compared in detail. Manual de novo sequencing utilizing the combination of high accuracy CID and ETD data and an acid-related cleavage yielded the N-terminal half of the sequence from the reduced species. The intact polypeptide, containing 3 disulfide bridges produced a series of unusual fragments in ion trap CID experiments: abundant internal amino acid losses were detected, and also one of the disulfide-linkage positions could be determined from fragments formed by the cleavage of two bonds. In addition, internal and c-type fragments were also observed.

  9. Nanomedicine: de novo design of nanodrugs

    NASA Astrophysics Data System (ADS)

    Yang, Zaixing; Kang, Seung-Gu; Zhou, Ruhong

    2013-12-01

    Phenomenal advances in nanotechnology and nanoscience have been accompanied by exciting progress in de novo design of nanomedicines. Nanoparticles with their large space of structural amenability and excellent mechanical and electrical properties have become ideal candidates for high efficacy nanomedicines in both diagnostics and therapeutics. The therapeutic nanomedicines can be further categorized into nanocarriers for conventional drugs and nanodrugs with direct curing of target diseases. Here we review some of the recent advances in de novo design of nanodrugs, with an emphasis on the molecular level understanding of their interactions with biological systems including key proteins and cell membranes. We also include some of the latest advances in the development of nanocarriers with both passive and active targeting for completeness. These studies may shed light on a better understanding of the molecular mechanisms behind these nanodrugs, and also provide new insights and direction for the future design of nanomedicines.

  10. De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

    PubMed Central

    Parmeggiani, Fabio; Velasco, D. Alejandro Fernandez; Höcker, Birte; Baker, David

    2015-01-01

    Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)8-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes. PMID:26595462

  11. Top-down analysis of protein samples by de novo sequencing techniques

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

    Vyatkina, Kira; Wu, Si; Dekker, Lennard J. M.

    MOTIVATION: Recent technological advances have made high-resolution mass spectrometers affordable to many laboratories, thus boosting rapid development of top-down mass spectrometry, and implying a need in efficient methods for analyzing this kind of data. RESULTS: We describe a method for analysis of protein samples from top-down tandem mass spectrometry data, which capitalizes on de novo sequencing of fragments of the proteins present in the sample. Our algorithm takes as input a set of de novo amino acid strings derived from the given mass spectra using the recently proposed Twister approach, and combines them into aggregated strings endowed with offsets. Themore » former typically constitute accurate sequence fragments of sufficiently well-represented proteins from the sample being analyzed, while the latter indicate their location in the protein sequence, and also bear information on post-translational modifications and fragmentation patterns.« less

  12. Nanomedicine: de novo design of nanodrugs.

    PubMed

    Yang, Zaixing; Kang, Seung-gu; Zhou, Ruhong

    2014-01-21

    Phenomenal advances in nanotechnology and nanoscience have been accompanied by exciting progress in de novo design of nanomedicines. Nanoparticles with their large space of structural amenability and excellent mechanical and electrical properties have become ideal candidates for high efficacy nanomedicines in both diagnostics and therapeutics. The therapeutic nanomedicines can be further categorized into nanocarriers for conventional drugs and nanodrugs with direct curing of target diseases. Here we review some of the recent advances in de novo design of nanodrugs, with an emphasis on the molecular level understanding of their interactions with biological systems including key proteins and cell membranes. We also include some of the latest advances in the development of nanocarriers with both passive and active targeting for completeness. These studies may shed light on a better understanding of the molecular mechanisms behind these nanodrugs, and also provide new insights and direction for the future design of nanomedicines.

  13. Wegener's granulomatosis occurring de novo during pregnancy.

    PubMed

    Alfhaily, F; Watts, R; Leather, A

    2009-01-01

    Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients.

  14. Further confirmation of the MED13L haploinsufficiency syndrome.

    PubMed

    van Haelst, Mieke M; Monroe, Glen R; Duran, Karen; van Binsbergen, Ellen; Breur, Johannes M; Giltay, Jacques C; van Haaften, Gijs

    2015-01-01

    MED13L haploinsufficiency syndrome has been described in two patients and is characterized by moderate intellectual disability (ID), conotruncal heart defects, facial abnormalities and hypotonia. Missense mutations in MED13L are linked to transposition of the great arteries and non-syndromal intellectual disability. Here we describe two novel patients with de novo MED13L aberrations. The first patient has a de novo mutation in the splice acceptor site of exon 5 of MED13L. cDNA analysis showed this mutation results in an in-frame deletion, removing 15 amino acids in middle of the conserved MED13L N-terminal domain. The second patient carries a de novo deletion of exons 6-20 of MED13L. Both patients show features of the MED13L haploinsufficiency syndrome, except for the heart defects, thus further confirming the existence of the MED13L haploinsufficiency syndrome.

  15. Improving prokaryotic transposable elements identification using a combination of de novo and profile HMM methods.

    PubMed

    Kamoun, Choumouss; Payen, Thibaut; Hua-Van, Aurélie; Filée, Jonathan

    2013-10-11

    Insertion Sequences (ISs) and their non-autonomous derivatives (MITEs) are important components of prokaryotic genomes inducing duplication, deletion, rearrangement or lateral gene transfers. Although ISs and MITEs are relatively simple and basic genetic elements, their detection remains a difficult task due to their remarkable sequence diversity. With the advent of high-throughput genome and metagenome sequencing technologies, the development of fast, reliable and sensitive methods of ISs and MITEs detection become an important challenge. So far, almost all studies dealing with prokaryotic transposons have used classical BLAST-based detection methods against reference libraries. Here we introduce alternative methods of detection either taking advantages of the structural properties of the elements (de novo methods) or using an additional library-based method using profile HMM searches. In this study, we have developed three different work flows dedicated to ISs and MITEs detection: the first two use de novo methods detecting either repeated sequences or presence of Inverted Repeats; the third one use 28 in-house transposase alignment profiles with HMM search methods. We have compared the respective performances of each method using a reference dataset of 30 archaeal and 30 bacterial genomes in addition to simulated and real metagenomes. Compared to a BLAST-based method using ISFinder as library, de novo methods significantly improve ISs and MITEs detection. For example, in the 30 archaeal genomes, we discovered 30 new elements (+20%) in addition to the 141 multi-copies elements already detected by the BLAST approach. Many of the new elements correspond to ISs belonging to unknown or highly divergent families. The total number of MITEs has even doubled with the discovery of elements displaying very limited sequence similarities with their respective autonomous partners (mainly in the Inverted Repeats of the elements). Concerning metagenomes, with the exception of short reads data (<300 bp) for which both techniques seem equally limited, profile HMM searches considerably ameliorate the detection of transposase encoding genes (up to +50%) generating low level of false positives compare to BLAST-based methods. Compared to classical BLAST-based methods, the sensitivity of de novo and profile HMM methods developed in this study allow a better and more reliable detection of transposons in prokaryotic genomes and metagenomes. We believed that future studies implying ISs and MITEs identification in genomic data should combine at least one de novo and one library-based method, with optimal results obtained by running the two de novo methods in addition to a library-based search. For metagenomic data, profile HMM search should be favored, a BLAST-based step is only useful to the final annotation into groups and families.

  16. Undermethylated DNA as a source of microsatellites from a conifer genome.

    PubMed

    Zhou, Y; Bui, T; Auckland, L D; Williams, C G

    2002-02-01

    Developing microsatellites from the large, highly duplicated conifer genome requires special tools. To improve the efficiency of developing Pinus taeda L. microsatellites, undermethylated (UM) DNA fragments were used to construct a microsatellite-enriched copy library. A methylation-sensitive restriction enzyme, McrBC, was used to enrich for UM DNA before library construction. Digested DNA fragments larger than 9 kb were then excised and digested with RsaI and used to construct nine dinucleotide and trinucleotide libraries. A total of 1016 microsatellite-positive clones were detected among 11 904 clones and 620 of these were unique. Of 245 primer sets that produced a PCR product, 113 could be developed as UM microsatellite markers and 70 were polymorphic. Inheritance and marker informativeness were tested for a random sample of 36 polymorphic markers using a three-generation outbred pedigree. Thirty-one microsatellites (86%) had single-locus inheritance despite the highly duplicated nature of the P. taeda genome. Nineteen UM microsatellites had highly informative intercross mating type configurations. Allele number and frequency were estimated for eleven UM microsatellites using a population survey. Allele numbers for these UM microsatellites ranged from 3 to 12 with an average of 5.7 alleles/locus. Frequencies for the 63 alleles were mostly in the low-common range; only 14 of the 63 were in the rare allele (q < 0.05) class. Enriching for UM DNA was an efficient method for developing polymorphic microsatellites from a large plant genome.

  17. VizieR Online Data Catalog: UKIDSS-DR8 LAS, GCS and DXS Surveys (Lawrence+ 2012)

    NASA Astrophysics Data System (ADS)

    Lawrence, A.; Warren, S. J.; Almaini, O.; Edge, A. C.; Hambly, N. C.; Jameson, R. F.; Lucas, P.; Casali, M.; Adamson, A.; Dye, S.; Emerson, J. P.; Foucaud, S.; Hewett, P.; Hirst, P.; Hodgkin, S. T.; Irwin, M. J.; Lodieu, N.; McMahon, R. G.; Simpson, C.; Smail, I.; Mortlock, D.; Folger, M.

    2012-03-01

    The UKIRT Infrared Deep Sky Survey (UKIDSS) is a large-scale near-IR survey which aim is to cover 7500 square degrees of the Northern sky. The survey is carried out using the Wide Field Camera (WFCAM), with a field of view of 0.21 square degrees, mounted on the 3.8m United Kingdom Infra-red Telescope (UKIRT) in Hawaii. The project comprises five surveys (LAS, GCS, DXS, GPS and UDS). The Large Area Survey (LAS) covers an area of 4000 square degrees in high Galactic latitudes (extragalactic) in the four bands Y(1.0um) J(1.2um) H(1.6um) and K(2.2um) to a depth of K=18.4. The Galactic Clusters Survey (GCS) aims to survey ten large open star clusters and star formation associations, covering a total of 1067 square degrees in the five bands Z (0.9um), Y(1.0um) J(1.2um) H(1.6um) and K(2.2um), plus a second pass in K for proper motions, to a depth of Z=20.4, Y=20.3, J=19.5, H=18.6, K=18.6. The Deep Extragalactic Survey (DXS) aims to map 35 square degrees of sky to a 5-σ point-source sensitivity of J=22.3 and K=20.8 in four carefully selected, multi-wavelength survey areas. The central regions of each field will also be mapped to H=21.8. The primary aim of the survey is to produce a photometric galaxy sample at a redshift of 1-2, within a volume comparable to that of the SDSS, selected in the same passband (rest frame optical). Details of the surveys can be found in the in the paper by Lawrence et al. (2007MNRAS.379.1599L), and at the UKIDSS Surveys site (http://www.ukidss.org/surveys/surveys.html). The data described here represent a subset of the UKIDSS data, limited to the public data and most representative columns. In the "Byte-by-byte Description" below the original names of the columns are given as bracketed names. (3 data files).

  18. Comparison of three assembly strategies for a heterozygous seedless grapevine genome assembly.

    PubMed

    Patel, Sagar; Lu, Zhixiu; Jin, Xiaozhu; Swaminathan, Padmapriya; Zeng, Erliang; Fennell, Anne Y

    2018-01-17

    De novo heterozygous assembly is an ongoing challenge requiring improved assembly approaches. In this study, three strategies were used to develop de novo Vitis vinifera 'Sultanina' genome assemblies for comparison with the inbred V. vinifera (PN40024 12X.v2) reference genome and a published Sultanina ALLPATHS-LG assembly (AP). The strategies were: 1) a default PLATANUS assembly (PLAT_d) for direct comparison with AP assembly, 2) an iterative merging strategy using METASSEMBLER to combine PLAT_d and AP assemblies (MERGE) and 3) PLATANUS parameter modifications plus GapCloser (PLAT*_GC). The three new assemblies were greater in size than the AP assembly. PLAT*_GC had the greatest number of scaffolds aligning with a minimum of 95% identity and ≥1000 bp alignment length to V. vinifera (PN40024 12X.v2) reference genome. SNP analysis also identified additional high quality SNPs. A greater number of sequence reads mapped back with zero-mismatch to the PLAT_d, MERGE, and PLAT*_GC (>94%) than was found in the AP assembly (87%) indicating a greater fidelity to the original sequence data in the new assemblies than in AP assembly. A de novo gene prediction conducted using seedless RNA-seq data predicted > 30,000 coding sequences for the three new de novo assemblies, with the greatest number (30,544) in PLAT*_GC and only 26,515 for the AP assembly. Transcription factor analysis indicated good family coverage, but some genes found in the VCOST.v3 annotation were not identified in any of the de novo assemblies, particularly some from  the MYB and ERF families. The PLAT_d and PLAT*_GC had a greater number of synteny blocks with the V. vinifera (PN40024 12X.v2) reference genome than AP or MERGE. PLAT*_GC provided the most contiguous assembly with only 1.2% scaffold N, in contrast to AP (10.7% N), PLAT_d (6.6% N) and Merge (6.4% N). A PLAT*_GC pseudo-chromosome assembly with chromosome alignment to the reference genome V. vinifera, (PN40024 12X.v2) provides new information for use in seedless grape genetic mapping studies. An annotated de novo gene prediction for the PLAT*_GC assembly, aligned with VitisNet pathways provides new seedless grapevine specific transcriptomic resource that has excellent fidelity with the seedless short read sequence data.

  19. Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study.

    PubMed

    Calabrese, Joseph R; Jin, Na; Johnson, Brian; Such, Pedro; Baker, Ross A; Madera, Jessica; Hertel, Peter; Ottinger, Jocelyn; Amatniek, Joan; Kawasaki, Hiroaki

    2018-06-10

    The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

  20. High-voltage leak detection of a parenteral proteinaceous solution product packaged in form-fill-seal plastic laminate bags. Part 2. Method performance as a function of heat seal defects, product-package refrigeration, and package plastic laminate lot.

    PubMed

    Rasmussen, Mats; Damgaard, Rasmus; Buus, Peter; Mulhall, Brian; Guazzo, Dana Morton

    2013-01-01

    Part 1 of this three-part research series detailed the development and validation of a high-voltage leak detection test (HVLD, also known as an electrical conductivity and capacitance test) for verifying the container-closure integrity of a small-volume laminate plastic bag containing an aqueous solution formulation of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. Leak detection capability was verified using positive controls each with a single laser-drilled hole in the bag film face. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect weaknesses and/or gaps in the bag heat seal. Study 2 checked the HVLD detection of bag holes in packages stored 4 days at ambient conditions followed by 17 days at refrigeration. Study 3 examined HVLD test results for packages tested when cold. Study 4 compared HVLD test results as a function of bag plastic film lots. The final Part 3 of this series will report the impact of HVLD exposure on product visual appearance and chemical stability. In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with a solution for injection of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect bag heat seal leaks. Study 2 checked HVLD's ability to detect bag holes after a total of 21 days at ambient plus refrigerated temperatures. Study 3 looked to see if HVLD results changed for packages tested when still cold. Study 4 compared HVLD results for multiple bag plastic film lots. The final Part 3 of this series will report any evidence of drug component degradation caused by HVLD exposure.

  1. Physiological, morphological and allocation plasticity of a semi-deciduous shrub

    NASA Astrophysics Data System (ADS)

    Zunzunegui, M.; Ain-Lhout, F.; Barradas, M. C. Díaz; Álvarez-Cansino, L.; Esquivias, M. P.; García Novo, F.

    2009-05-01

    The main objective of this study was to look into the phenotypic plasticity of the semi-deciduous Mediterranean shrub, Halimium halimifolium. We studied morphological, allocation and physiological traits to determine which characters were more plastic and contribute in a greater extent to the acclimation ability of the species. We present a phenotypic plasticity index for morphological, physiological and allocation traits, which we have applied in the most contrasted plant communities where the species grows naturally. Data published by Díaz Barradas, M.C., García Novo, F. [1987. The vertical structure of Mediterranean scrub in Doñana National Park (SW Spain). Folia Geobotanica Phytotaxonomica 22, 415-433; 1988. Modificación y extinción de la luz a través de la copa en cuatro especies de matorral en el Parque Nacional de Doñana. Monografias Instituto Pirenaico de Ecologia 4, 503-516; 1990. Seasonal changes in canopy structure in two mediterranean dune shrubs. Journal of Vegetation Science 1, 31-40.], Díaz Barradas, M.C., Zunzunegui, M., García Novo, F. [1999a. Autoecological traits of Halimium halimifolium in contrasted habitats under Mediterranean type climate. Folia Geobotanica 34, 189-208.] and Zunzunegui et al. [Zunzunegui, M., Díaz Barradas, M.C., García Novo, F. 1997. Autoecological notes of Halimium halimifolium. Lagascalia 19, 725-736. Sevilla, Spain; Zunzunegui, M., Díaz Barradas, M.C., Fernández Baco, L., García Novo, F. 1999. Seasonal changes in photochemical efficiency in leaves of Halimium halimifolium a Mediterranean semideciduous shrub. Photosynthetica 36, 17-31; Zunzunegui, M., Díaz Barradas, M.C., García Novo, F. 2000. Different phenotypic response of Halimium halimifolium in relation to groundwater availability. Plant Ecology 148, 165-174; Zunzunegui, M., Díaz Barradas, M.C., Aguilar, F., Ain-Lhout, F., Clavijo, A., García Novo, F. 2002. Growth response of Halimium halimifolium at four sites with different soil water availability regimes in two contrasted hydrological cycles. Plant and Soil 247, 271-28.] have been re-appraised and combined with original data. Phenotypic plasticity index showed that the highest plasticity of the species was physiological, and especially for the traits related with water control. This high physiological plasticity appears mainly between seasons (September-November) rather than between sites. Plasticity in allocation traits showed intermediate values between physiological and morphological traits.

  2. HOW TO ACHIEVE AND MAINTAIN NOTE 6: POSTGRADUATE PROGRAM IN TRANSLATIONAL SURGERY - UNIFESP.

    PubMed

    Sabino-Neto, Miguel; Ferreira, Lydia Masako

    2015-01-01

    To show the way to reach and stay in note 6 in the evaluation process of Medicine III of CAPES. Capes determinations were reviewed concerning this topic, grades 6 and 7, and also the difficulties and facilities of running a program that amounted to Note 6 after restructuring and being in compliance with regulations. The main points to achieve and maintain Note 6 were: 1) regular production of master's and doctoral theses with appropriate distribution among all teachers; 2) average time of appropriate titration, as well as strict selection of students who resets the withdrawals and cancellations; 3) production of scientific articles in high impact journals and with academic and student participation in most part; 4) progressive and substantial increase in fundraising and patent search; 5) progressive increase in international exchanges with joint production; 6) visibility through new bilingual website and updated weekly; 7) numerous solidarity activities in research, but also in health services for the population and even in basic education; 8) rigorous selection of students (through design analysis, curriculum and teacher training program); 9) maintenance of high levels teachers production; 10) preparing new teachers for guidance through participation as co-supervision and involvement in the program to fit the needs. The Postgraduate Program in Translational Surgery went through difficult times; was submitted to a series of measures, adjustments, cooperation and understanding of the teaching staff, that took the program from note 3 - and almost closing - to a level of excellence keeping note 6 for three consecutive three-year periods of evaluation. Mostrar o caminho para alcançar e se manter na nota 6 no processo de avaliação da Medicina III da Capes. Foram revisadas as determinações da Capes concernentes ao tema, conceitos 6 e 7, e também as dificuldades e facilidades próprias da execução de um programa que ascendeu à nota 6 após reestruturação e adequação às normas vigentes. Os pontos principais para alcançar e manter conceito 6 foram: : 1) produção regular de teses de mestrado e doutorado com distribuição adequada entre todos os orientadores; 2) tempo médio de titulação adequado, assim como rígida seleção do alunado que zera as desistências e cancelamentos; 3) produção de artigos científicos alta em revistas de impacto e com participação docente e discente na sua grande maioria; 4) aumento progressivo e substancial da captação de recursos e busca de patentes; 5) aumento progressivo dos intercâmbios internacionais com produção conjunta; 6) visibilidade através de novo site bilíngue e atualizado semanalmente; 7) inúmeras atividades de solidariedade em pesquisa, mas também em Serviços de Saúde para a população e mesmo no ensino básico; 8) rigorosa seleção dos alunos (através de análise de projeto, currículo e programa de estágio docente); 9) manutenção de índices elevados de produção dos docentes; 10) preparação de novos docentes para orientação através de participação como co-orientação e envolvimento no programa para se adequar às necessidades. O Programa de Pós-Graduação em Cirurgia Translacional passou por momentos difíceis e que através de uma série de medidas, ajustes e a colaboração e compreensão do seu corpo docente pode sair da nota 3 e quase fechamento, para um nível de excelência mantendo nota 6 em três triênios seguidos.

  3. Study on extrusion process of SiC ceramic matrix

    NASA Astrophysics Data System (ADS)

    Dai, Xiao-Yuan; Shen, Fan; Ji, Jia-You; Wang, Shu-Ling; Xu, Man

    2017-11-01

    In this thesis, the extrusion process of SiC ceramic matrix has been systematically studied.The effect of different cellulose content on the flexural strength and pore size distribution of SiC matrix was discussed.Reselts show that with the increase of cellulose content, the flexural strength decreased.The pore size distribution in the sample was 1um-4um, and the 1um-2um concentration was more concentrated. It is found that the cellulose content has little effect on the pore size distribution.When the cellulose content is 7%, the flexural strength of the sample is 40.9Mpa. At this time, the mechanical properties of the sample are the strongest.

  4. Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy.

    PubMed

    Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

    2015-01-01

    The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration.

  5. Primary intraosseous squamous cell carcinoma of the mandible arising de novo.

    PubMed

    Shamim, Thorakkal

    2009-07-01

    Primary intraosseous squamous cell carcinoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th to 7th decades of life. The tumour is characterized by progressive swelling of the jaw, pain and loosening of teeth. Microscopically, the lesion is showing foci of keratinising cells separated by collagenous connective tissue stroma. A case of primary intraosseous squamous cell carcinoma of mandible arising de novo in a 40-year-old man is reported.

  6. Creatine and guanidinoacetate content of human milk and infant formulas: implications for creatine deficiency syndromes and amino acid metabolism.

    PubMed

    Edison, Erica E; Brosnan, Margaret E; Aziz, Khalid; Brosnan, John T

    2013-09-28

    Creatine is essential for normal neural development; children with inborn errors of creatine synthesis or transport exhibit neurological symptoms such as mental retardation, speech delay and epilepsy. Creatine accretion may occur through dietary intake or de novo creatine synthesis. The objective of the present study was to determine how much creatine an infant must synthesise de novo. We have calculated how much creatine an infant needs to account for urinary creatinine excretion (creatine's breakdown product) and new muscle lay-down. To measure an infant's dietary creatine intake, we measured creatine in mother's milk and in various commercially available infant formulas. Knowing the amount of milk/formula ingested, we calculated the amount of creatine ingested. We have found that a breast-fed infant receives about 9 % of the creatine needed in the diet and that infants fed cows' milk-based formula receive up to 36 % of the creatine needed. However, infants fed a soya-based infant formula receive negligible dietary creatine and must rely solely on de novo creatine synthesis. This is the first time that it has been shown that neonatal creatine accretion is largely due to de novo synthesis and not through dietary intake of creatine. This has important implications both for infants suffering from creatine deficiency syndromes and for neonatal amino acid metabolism.

  7. Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting.

    PubMed

    Bhoo-Pathy, Nirmala; Verkooijen, Helena Marieke; Tan, Ern-Yu; Miao, Hui; Taib, Nur Aishah Mohd; Brand, Judith S; Dent, Rebecca A; See, Mee-Hoong; Subramaniam, ShriDevi; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har

    2015-11-05

    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.

  8. A novel approach using long‐read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders

    PubMed Central

    Gudmundsson, Sanna; Johansson, Josefin; Ameur, Adam; Stattin, Eva‐Lena; Annerén, Göran; Malmgren, Helena; Frykholm, Carina

    2017-01-01

    Abstract Objective De novo mutations contribute significantly to severe early‐onset genetic disorders. Even if the mutation is apparently de novo, there is a recurrence risk due to parental germ line mosaicism, depending on in which gonadal generation the mutation occurred. Methods We demonstrate the power of using SMRT sequencing and ddPCR to determine parental origin and allele frequencies of de novo mutations in germ cells in two families whom had undergone assisted reproduction. Results In the first family, a TCOF1 variant c.3156C>T was identified in the proband with Treacher Collins syndrome. The variant affects splicing and was determined to be of paternal origin. It was present in <1% of the paternal germ cells, suggesting a very low recurrence risk. In the second family, the couple had undergone several unsuccessful pregnancies where a de novo mutation PTPN11 c.923A>C causing Noonan syndrome was identified. The variant was present in 40% of the paternal germ cells suggesting a high recurrence risk. Conclusions Our findings highlight a successful strategy to identify the parental origin of mutations and to investigate the recurrence risk in couples that have undergone assisted reproduction with an unknown donor or in couples with gonadal mosaicism that will undergo preimplantation genetic diagnosis. PMID:28921562

  9. A novel approach using long-read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders.

    PubMed

    Wilbe, Maria; Gudmundsson, Sanna; Johansson, Josefin; Ameur, Adam; Stattin, Eva-Lena; Annerén, Göran; Malmgren, Helena; Frykholm, Carina; Bondeson, Marie-Louise

    2017-11-01

    De novo mutations contribute significantly to severe early-onset genetic disorders. Even if the mutation is apparently de novo, there is a recurrence risk due to parental germ line mosaicism, depending on in which gonadal generation the mutation occurred. We demonstrate the power of using SMRT sequencing and ddPCR to determine parental origin and allele frequencies of de novo mutations in germ cells in two families whom had undergone assisted reproduction. In the first family, a TCOF1 variant c.3156C>T was identified in the proband with Treacher Collins syndrome. The variant affects splicing and was determined to be of paternal origin. It was present in <1% of the paternal germ cells, suggesting a very low recurrence risk. In the second family, the couple had undergone several unsuccessful pregnancies where a de novo mutation PTPN11 c.923A>C causing Noonan syndrome was identified. The variant was present in 40% of the paternal germ cells suggesting a high recurrence risk. Our findings highlight a successful strategy to identify the parental origin of mutations and to investigate the recurrence risk in couples that have undergone assisted reproduction with an unknown donor or in couples with gonadal mosaicism that will undergo preimplantation genetic diagnosis. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.

  10. Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

    PubMed

    Allen, Richard J; Musante, Cynthia J

    2017-01-01

    Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

  11. Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

    PubMed Central

    Allen, Richard J; Musante, Cynthia J

    2017-01-01

    Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole. PMID:28469410

  12. Detection of de novo single nucleotide variants in offspring of atomic-bomb survivors close to the hypocenter by whole-genome sequencing.

    PubMed

    Horai, Makiko; Mishima, Hiroyuki; Hayashida, Chisa; Kinoshita, Akira; Nakane, Yoshibumi; Matsuo, Tatsuki; Tsuruda, Kazuto; Yanagihara, Katsunori; Sato, Shinya; Imanishi, Daisuke; Imaizumi, Yoshitaka; Hata, Tomoko; Miyazaki, Yasushi; Yoshiura, Koh-Ichiro

    2018-03-01

    Ionizing radiation released by the atomic bombs at Hiroshima and Nagasaki, Japan, in 1945 caused many long-term illnesses, including increased risks of malignancies such as leukemia and solid tumours. Radiation has demonstrated genetic effects in animal models, leading to concerns over the potential hereditary effects of atomic bomb-related radiation. However, no direct analyses of whole DNA have yet been reported. We therefore investigated de novo variants in offspring of atomic-bomb survivors by whole-genome sequencing (WGS). We collected peripheral blood from three trios, each comprising a father (atomic-bomb survivor with acute radiation symptoms), a non-exposed mother, and their child, none of whom had any past history of haematological disorders. One trio of non-exposed individuals was included as a control. DNA was extracted and the numbers of de novo single nucleotide variants in the children were counted by WGS with sequencing confirmation. Gross structural variants were also analysed. Written informed consent was obtained from all participants prior to the study. There were 62, 81, and 42 de novo single nucleotide variants in the children of atomic-bomb survivors, compared with 48 in the control trio. There were no gross structural variants in any trio. These findings are in accord with previously published results that also showed no significant genetic effects of atomic-bomb radiation on second-generation survivors.

  13. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype.

    PubMed

    Beaujard, M-P; Jouannic, J-M; Bessières, B; Borie, C; Martin-Luis, I; Fallet-Bianco, C; Portnoï, M-F

    2005-06-01

    To present the prenatal diagnosis of a de novo terminal inversion duplication of the short arm of chromosome 4 and a review of the literature. An amniocentesis for chromosome analysis was performed at 33 weeks' gestation because ultrasound examination showed a female fetus with multiple abnormalities consisting of severe intrauterine growth retardation, microcephaly, a cleft lip and renal hypoplasia. Cytogenetic analysis and FISH studies of the cultured amniocytes revealed a de novo terminal inversion duplication of the short arm of chromosome 4 characterized by a duplication of 4p14-p16.1 chromosome region concomitant with a terminal deletion 4p16.1-pter. The karyotype was thus: 46,XX, inv dup del (4)(:p14-->p16.1::p16.1-->qter). The parents opted to terminate the pregnancy. Fetopathological examination showed dysmorphic features and abnormalities consistent with a Wolf-Hirschhorn syndrome (WHS) diagnosis, clinical manifestations of partial 4p trisomy being mild. Although relatively rare, inverted duplications have been reported repeatedly in an increasing number of chromosomes. Only two previous cases with de novo inv dup del (4p) and one with tandem dup 4p have been reported, all of them associated with a 4pter deletion. We report the first case diagnosed prenatally. Breakpoints are variable, resulting in different abnormal phenotype. In our case, clinical manifestations resulted in a WHS phenotype.

  14. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

    PubMed

    Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

    2013-12-01

    De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

  15. Essential role of Bordetella NadC in a quinolinate salvage pathway for NAD biosynthesis.

    PubMed

    Brickman, Timothy J; Suhadolc, Ryan J; McKelvey, Pamela J; Armstrong, Sandra K

    2017-02-01

    Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase. Genomic analyses of taxonomically related Bordetella and Achromobacter species also indicated the presence of an 'orphan' nadC and the absence of nadA and nadB. When supplied as the sole NAD precursor, quinolinate promoted B. bronchiseptica growth, and the ability to use it required nadC. Co-expression of Bordetella nadC with the nadB and nadA genes of Paraburkholderia phytofirmans allowed B. bronchiseptica to grow in the absence of supplied pyridines, indicative of de novo NAD synthesis and functional confirmation of Bordetella NadC activity. Expression of nadC in B. bronchiseptica was influenced by nicotinic acid and by a NadQ family transcriptional repressor, indicating that these organisms prioritize their use of pyridines for NAD biosynthesis. © 2016 John Wiley & Sons Ltd.

  16. De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

    PubMed Central

    Guella, Ilaria; Huh, Linda; McKenzie, Marna B.; Toyota, Eric B.; Bebin, E. Martina; Thompson, Michelle L.; Cooper, Gregory M.; Evans, Daniel M.; Buerki, Sarah E.; Adam, Shelin; Van Allen, Margot I.; Nelson, Tanya N.; Connolly, Mary B.; Farrer, Matthew J.

    2016-01-01

    Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report. PMID:27872899

  17. Exploring the combinatorial space of complete pathways to chemicals.

    PubMed

    Wang, Lin; Ng, Chiam Yu; Dash, Satyakam; Maranas, Costas D

    2018-04-06

    Computational pathway design tools often face the challenges of balancing the stoichiometry of co-metabolites and cofactors, and dealing with reaction rule utilization in a single workflow. To this end, we provide an overview of two complementary stoichiometry-based pathway design tools optStoic and novoStoic developed in our group to tackle these challenges. optStoic is designed to determine the stoichiometry of overall conversion first which optimizes a performance criterion (e.g. high carbon/energy efficiency) and ensures a comprehensive search of co-metabolites and cofactors. The procedure then identifies the minimum number of intervening reactions to connect the source and sink metabolites. We also further the pathway design procedure by expanding the search space to include both known and hypothetical reactions, represented by reaction rules, in a new tool termed novoStoic. Reaction rules are derived based on a mixed-integer linear programming (MILP) compatible reaction operator, which allow us to explore natural promiscuous enzymes, engineer candidate enzymes that are not already promiscuous as well as design de novo enzymes. The identified biochemical reaction rules then guide novoStoic to design routes that expand the currently known biotransformation space using a single MILP modeling procedure. We demonstrate the use of the two computational tools in pathway elucidation by designing novel synthetic routes for isobutanol. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  18. Infant mortality in Novo Hamburgo: associated factors and cardiovascular causes.

    PubMed

    Brum, Camila de Andrade; Stein, Airton Tetelbom; Pellanda, Lucia Campos

    2015-04-01

    Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables 'age at death', 'gestational age' and 'birth weight'. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

  19. Plasma HVA levels following debrisoquine administration do not reflect cerebral dopamine loss in early Parkinson's disease.

    PubMed

    Rose, S; Hindmarsh, J G; Steiger, M J; Bhatt, M; Quinn, N P; Jenner, P; Marsden, C D

    1994-06-01

    Plasma levels of homovanillic acid (pHVA) following debrisoquine (DBQ) administration may be indicative of central dopaminergic activity. The effect of DBQ (10-20 mg) administration on pHVA in young healthy volunteers was studied to establish a protocol for use in de novo patients with Parkinson's disease. Subsequently, pHVA in de novo patients with Parkinson's disease were measured and compared to young healthy volunteers. Following DBQ (10 mg) administration to healthy volunteers, pHVA fell with time to a maximum of 62% of control values at 6 h. The decrease in pHVA was not affected by loading with DBQ (10 mg) 10 h previously (pHVA: 67.6 +/- 5.8% of preDBQ levels) or increasing the dose to 20 mg (56.1 +/- 11.8% of preDBQ levels) compared to a single 10 mg dose of debrisoquine (66.5 +/- 4.5% of preDBQ levels). pHVA was reduced in both de novo patients with Parkinson's disease and in healthy volunteers following DBQ (10 mg) administration. However, there was no difference in pHVA before or after DBQ administration when comparing the two groups. These results suggest that, following DBQ administration, pHVA does not reflect dopamine neuronal loss in de novo patients with Parkinson's disease, so it is unlikely to detect the disease before the clinical symptoms manifest themselves.

  20. First de novo whole genome sequencing and assembly of the pink-footed goose.

    PubMed

    Pujolar, J M; Dalén, L; Olsen, R A; Hansen, M M; Madsen, J

    2018-03-01

    Annotated genomes can provide new perspectives on the biology of species. We present the first de novo whole genome sequencing for the pink-footed goose. In order to obtain a high-quality de novo assembly the strategy used was to combine one short insert paired-end library with two mate-pair libraries. The pink-footed goose genome was assembled de novo using three different assemblers and an assembly evaluation was subsequently performed in order to choose the best assembler. For our data, ALLPATHS-LG performed the best, since the assembly produced covers most of the genome, while introducing the fewest errors. A total of 26,134 genes were annotated, with bird species accounting for virtually all BLAST hits. We also estimated the substitution rate in the pink-footed goose, which can be of use in future demographic studies, by using a comparative approach with the genome of the chicken, the mallard and the swan goose. A substitution rate of 1.38×10 -7 per nucleotide per generation was obtained when comparing the genomes of the two closely-related goose species (the pink-footed and the swan goose). Altogether, we provide a valuable tool for future genomic studies aiming at particular genes and regions of the pink-footed goose genome as well as other bird species. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II.

    PubMed

    Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan

    2014-06-01

    Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral cortex by triazolobenzodiazepines

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

    Obata, T.; Yamamura, H.I.

    1988-01-01

    The effects of triazolobenzodiazepines of GABA-stimulated /sup 36/Cl/sup -/ uptake by membrane vesicles from rat cerebral cortex were examined. Triazolam and alprazolam showed a significant enhancement of GABA-stimulated /sup 36/Cl/sup -/ uptake at 0.01-10 uM. On the other hand, adinazolam showed a small enhancement at 0.1-1 uM followed by a significant inhibition of GABA-stimulated /sup 36/Cl/sup -/ uptake at 100 uM. The enhancement of GABA-stimulated /sup 36/Cl/sup -/ uptake by 1 uM alprazolam was antagonized by Ro15-1788, a benzodiazepine antagonist, but the inhibition of this response by 30 uM adinazolam was not antagonized by Ro15-1788. These results indicate that triazolobenzodiazepinesmore » enhanced GABA-stimulated /sup 36/Cl/sup -/ uptake through benzodiazepine receptors. High concentrations of adinazolam inhibit GABA-stimulated /sup 36/Cl/sup -/ uptake which may be due to the direct blockade of GABA-gated chloride channel. 23 references, 4 figures.« less

  3. Selumetinib-based therapy in uveal melanoma patient-derived xenografts

    PubMed Central

    Decaudin, Didier; El Botty, Rania; Diallo, Béré; Massonnet, Gerald; Fleury, Justine; Naguez, Adnan; Raymondie, Chloé; Davies, Emma; Smith, Aaron; Wilson, Joanne; Howes, Colin; Smith, Paul D.; Cassoux, Nathalie; Piperno-Neumann, Sophie; Roman-Roman, Sergio; Némati, Fariba

    2018-01-01

    The prognosis of metastatic uveal melanoma (UM) is among the worst of all human cancers. The identification of near-ubiquitous GNAQ/GNA11 mutations and the activation of MAPK signaling in UM have raised hopes of more effective, targeted therapies, based on MEK inhibition, for example. We evaluated the potential of drug combinations to increase the efficacy of the MEK inhibitor selumetinib (AZD6244, ARRY-142886), in UM cell lines and Patient-Derived Xenografts. We first evaluated the combination of selumetinib and DTIC. We found that DTIC did not improve the in vitro or in vivo antitumor efficacy of selumetinib, consistent with the outcome of the SUMIT clinical trial assessing the efficacy of this combination in UM. We then tested additional selumetinib combinations with the chemotherapy agent docetaxel, the ERK inhibitor AZ6197, and the mTORC1/2 inhibitor, vistusertib (AZD2014). Combinations of selumetinib with ERK and mTORC1/2 inhibitors appeared to be the most effective in UM PDX models. PMID:29774094

  4. Immunostaining, dehydration, and clearing of mouse embryos for ultramicroscopy.

    PubMed

    Becker, Klaus; Jährling, Nina; Saghafi, Saiedeh; Dodt, Hans-Ulrich

    2013-08-01

    This protocol describes the preparation of mouse embryos for ultramicroscopy (UM), a powerful imaging technique that achieves precise and accurate three-dimensional (3D) reconstructions of intact macroscopic specimens with micrometer resolution. In UM, a specimen in the size range of ∼1-15 mm is illuminated perpendicular to the observation pathway by two thin counterpropagating sheets of laser light. In combination with fluorescein isothiocyanate (FITC) immunostaining, UM allows visualization of somatic motor and sensorial nerve fibers in whole mouse embryos. Even the fine branches of the sensomotoric fibers can be visualized over a distance of up to several millimeters. In this protocol, mouse embryos are fixed and immunostained in preparation for UM. Because UM requires the excitation light sheet to travel throughout the entire horizontal width of the specimen, specimens usually have to be rendered transparent before microscope inspection. Here, the embryos are dehydrated in ethanol and then cleared in a solution of benzyl alcohol and benzyl benzoate.

  5. The mental health of unaccompanied refugee minors on arrival in the host country.

    PubMed

    Vervliet, Marianne; Meyer Demott, Melinda A; Jakobsen, Marianne; Broekaert, Eric; Heir, Trond; Derluyn, Ilse

    2014-02-01

    Despite increasing numbers of unaccompanied refugee minors (UM) in Europe and heightened concerns for this group, research on their mental health has seldom included the factor "time since arrival." As a result, our knowledge of the mental health statuses of UM at specific points in time and over periods in their resettlement trajectories in European host countries is limited. This study therefore examined the mental health of UM shortly after their arrival in Norway (n = 204) and Belgium (n = 103) through the use of self-report questionnaires (HSCL-37A, SLE, RATS, HTQ). High prevalence scores of anxiety, depression and posttraumatic stress disorder (PTSD) symptoms were found. In addition, particular associations were found with the number of traumatic events the UM reported. The results indicate that all UM have high support needs on arrival in the host country. Longitudinal studies following up patterns of continuity and change in their mental health during their trajectories in the host country are necessary. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  6. Driving bubbles out of glass

    NASA Technical Reports Server (NTRS)

    Mattox, D. M.

    1981-01-01

    Surface tension gradient in melt forces gas bubbles to surface, increasing glass strength and transparency. Conventional chemical and buoyant fining are extremely slow in viscous glasses, but tension gradient method moves 250 um bubbles as rapidly as 30 um/s. Heat required for high temperature part of melt is furnished by stationary electrical or natural-gas heater; induction and laser heating are also possible. Method has many applications in industry processes.

  7. Genetic heterogeneity in uveal melanoma assessed by multiplex ligation-dependent probe amplification.

    PubMed

    Dopierala, Justyna; Damato, Bertil E; Lake, Sarah L; Taktak, Azzam F G; Coupland, Sarah E

    2010-10-01

    To determine intratumor genetic heterogeneity in uveal melanoma (UM) by multiplex ligation-dependent probe amplification (MLPA) in formalin-fixed, paraffin-embedded (FFPE) tumor tissues. DNA was extracted from whole tumor sections and from two to nine different areas microdissected from 32 FFPE UMs. Thirty-one loci on chromosomes 1, 3, 6, and 8 were tested with MLPA for copy number changes. The tumor was considered heterogeneous at a locus if (1) the difference in dosage quotients (DQs) of any two areas was 0.2 or more, and (2) the DQs of the areas belonged to different ranges. Comparison of MLPA data obtained from microdissected areas of the UMs showed heterogeneity in 1 to 26 examined loci in 24 (75%) tumors, with only 25% of the tumors being homogeneous. Intratumor heterogeneity of 3p12.2, 6p21.2, and 8q11.23 was most common, occurring in >30% of the UMs. Gains of chromosome 3 were observed in four UMs, with three of these tumors showing the highest degree of heterogeneity. Copy number variation was associated with differences in tumor cell type, but not with differences in tumor pigmentation or reactive inflammation. UMs with genetic heterogeneity across multiple sample sites showed equivocal MLPA results when the whole tumor section was examined. These results suggest that different clones dilute MLPA results. Heterogeneity of chromosomal abnormalities of chromosomes 1, 3, 6, and 8 is present in most UMs. This heterogeneity causes equivocal MLPA results. One random tumor sample may not be representative of the whole tumor and, therefore, may be insufficient for prognostic testing.

  8. Genomic insight into pathogenicity of dematiaceous fungus Corynespora cassiicola

    PubMed Central

    Looi, Hong Keat; Toh, Yue Fen; Yew, Su Mei; Na, Shiang Ling; Tan, Yung-Chie; Chong, Pei-Sin; Khoo, Jia-Shiun; Yee, Wai-Yan; Ng, Kee Peng

    2017-01-01

    Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient’s contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases. The assembly size of UM 591 genome is 41.8 Mbp, and a total of 13,531 (≥99 bp) genes have been predicted. UM 591 is enriched with genes that encode for glycoside hydrolases, carbohydrate esterases, auxiliary activity enzymes and cell wall degrading enzymes. Virulent genes comprising of CAZymes, peptidases, and hypervirulence-associated cutinases were found to be present in the fungal genome. Comparative analysis result shows that UM 591 possesses higher number of carbohydrate esterases family 10 (CE10) CAZymes compared to other species of fungi in this study, and these enzymes hydrolyses wide range of carbohydrate and non-carbohydrate substrates. Putative melanin, siderophore, ent-kaurene, and lycopene biosynthesis gene clusters are predicted, and these gene clusters denote that UM 591 are capable of protecting itself from the UV and chemical stresses, allowing it to adapt to different environment. Putative sterigmatocystin, HC-toxin, cercosporin, and gliotoxin biosynthesis gene cluster are predicted. This finding have highlighted the necrotrophic and invasive nature of UM 591. PMID:28149676

  9. Origins Space Telescope: The Far Infrared Imager and Polarimeter FIP

    NASA Astrophysics Data System (ADS)

    Staguhn, Johannes G.; Chuss, David; Howard, Joseph; Meixner, Margaret; Vieira, Joaquin; Amatucci, Edward; Bradley, Damon; Carter, Ruth; Cooray, Asantha; Flores, Anel; Leisawitz, David; Moseley, Samuel Harvey; Wollack, Edward; Origins Space Telescope Study Team

    2018-01-01

    The Origins Space Telescope (OST)* is the mission concept for the Far-Infrared Surveyor, one of the four science and technology definition studies of NASA Headquarters for the 2020 Astronomy and Astrophysics Decadal survey. The current "concept 1", which envisions a cold (4K) 9m space telescope, includes 5 instruments, providing a wavelength coverage ranging from 6um and 667um. The achievable sensitivity of the observatory will provide three to four orders of magnitude of improvement in sensitivity over current observational capabilities, allowing to address a wide range of new and so far inaccessible scientific questions, ranging from bio-signatures on exo-planets to mapping primordial H_2 from the "dark ages" before the universe went through the phase of re-ionization.Here we present the Far Infrared Imager and Polarimeter (FIP) for OST. The cameral will cover four bands, 40um, 80um, 120um, and 240um. It will allow for differential polarimetry in those bands with the ability to observe two colors in polarimtery mode simultaneously, while all four bands can be observed simultaneously in total power mode. While the confusion limit will be reached in only 32ms at 240um, at 40um the source density on the sky is so low, that at the angular resolution of 1" of OST at this wavelength there will be no source confusion, even for the longest integration times. Science topics that can be addressed by FIP include but are not limited to galactic and extragalactic magnetic field studies, Deep Galaxy Surveys, and Outer Solar System objects..*Origins will enable flagship-quality general observing programs led by the astronomical community in the 2030s. We welcome you to contact the Science and Technology Definition Team (STDT) with your science needs and ideas by emailing us at ost_info@lists.ipac.caltech.edu

  10. Measuring Broadband IR Irradiance in the Direct Solar Beam and Recent Developments

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

    Reda, Ibrahim; Andreas, Afshin; Dooraghi, Mike

    2016-12-14

    Solar and atmospheric science radiometers such as pyranometers, pyrheliometers, and photovoltaic cells are calibrated with traceability to a consensus reference which is maintained by Absolute Cavity Radiometers (ACRs). An ACR is an open cavity with no window, developed to measure the extended broadband spectrum of the terrestrial direct solar beam irradiance that extends beyond the ultraviolet and infrared bands; i.e. below 0.2 um and above 50 um, respectively. On the other hand, the pyranometers and pyrheliometers were developed to measure broadband shortwave irradiance from approximately 0.3 um to 3 um, while the present photovoltaic cells are limited to the spectralmore » range of approximately 0.3 um to 1 um. The broadband mismatch of ACR versus such radiometers causes discrepancy in radiometers' calibration methods that has not been discussed or addressed in the solar and atmospheric science literature. Pyrgeometers, which measure the atmospheric longwave irradiance, are also used for solar and atmospheric science applications and calibrated with traceability to a consensus reference, yet they are calibrated during nighttime only, because no consensus reference has been established for the daytime longwave irradiance. This poster describes a method to measure the broadband longwave irradiance in the terrestrial direct solar beam from 3 um to 50 um, as a first step that might be used to help develop calibration methods to address the mismatch between broadband ACR and shortwave radiometers, and the lack of a daytime reference for pyrgeometers. The described method is used to measure the irradiance from sunrise to sunset; the irradiance varied from approximately 1 Wm-2 to 16 Wm-2 with an estimated uncertainty of 1.5 Wm-2, for a solar zenith angle range from 80 degrees to 16 degrees, respectively. Recent development shows that there is greater than 1.1 percent bias in measuring shortwave solar irradiance.« less

  11. Identification of optimum sequencing depth especially for de novo genome assembly of small genomes using next generation sequencing data.

    PubMed

    Desai, Aarti; Marwah, Veer Singh; Yadav, Akshay; Jha, Vineet; Dhaygude, Kishor; Bangar, Ujwala; Kulkarni, Vivek; Jere, Abhay

    2013-01-01

    Next Generation Sequencing (NGS) is a disruptive technology that has found widespread acceptance in the life sciences research community. The high throughput and low cost of sequencing has encouraged researchers to undertake ambitious genomic projects, especially in de novo genome sequencing. Currently, NGS systems generate sequence data as short reads and de novo genome assembly using these short reads is computationally very intensive. Due to lower cost of sequencing and higher throughput, NGS systems now provide the ability to sequence genomes at high depth. However, currently no report is available highlighting the impact of high sequence depth on genome assembly using real data sets and multiple assembly algorithms. Recently, some studies have evaluated the impact of sequence coverage, error rate and average read length on genome assembly using multiple assembly algorithms, however, these evaluations were performed using simulated datasets. One limitation of using simulated datasets is that variables such as error rates, read length and coverage which are known to impact genome assembly are carefully controlled. Hence, this study was undertaken to identify the minimum depth of sequencing required for de novo assembly for different sized genomes using graph based assembly algorithms and real datasets. Illumina reads for E.coli (4.6 MB) S.kudriavzevii (11.18 MB) and C.elegans (100 MB) were assembled using SOAPdenovo, Velvet, ABySS, Meraculous and IDBA-UD. Our analysis shows that 50X is the optimum read depth for assembling these genomes using all assemblers except Meraculous which requires 100X read depth. Moreover, our analysis shows that de novo assembly from 50X read data requires only 6-40 GB RAM depending on the genome size and assembly algorithm used. We believe that this information can be extremely valuable for researchers in designing experiments and multiplexing which will enable optimum utilization of sequencing as well as analysis resources.

  12. De novo autoimmune hepatitis after liver transplantation.

    PubMed

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

    2007-10-01

    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin inhibitors supports the view held by most specialists in autoimmune hepatitis that these drugs, even though effective in acute disease, are not helpful in the long-term management of autoimmune liver diseases.

  13. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.

    PubMed

    Barclay, Sarah F; Rand, Casey M; Borch, Lauren A; Nguyen, Lisa; Gray, Paul A; Gibson, William T; Wilson, Richard J A; Gordon, Paul M K; Aung, Zaw; Berry-Kravis, Elizabeth M; Ize-Ludlow, Diego; Weese-Mayer, Debra E; Bech-Hansen, N Torben

    2015-08-25

    Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation.

  14. Cancer Cells Differentially Activate and Thrive on De Novo Lipid Synthesis Pathways in a Low-Lipid Environment

    PubMed Central

    Daniëls, Veerle W.; Smans, Karine; Royaux, Ines; Chypre, Melanie

    2014-01-01

    Increased lipogenesis is a hallmark of a wide variety of cancers and is under intense investigation as potential antineoplastic target. Although brisk lipogenesis is observed in the presence of exogenous lipids, evidence is mounting that these lipids may adversely affect the efficacy of inhibitors of lipogenic pathways. Therefore, to fully exploit the therapeutic potential of lipid synthesis inhibitors, a better understanding of the interrelationship between de novo lipid synthesis and exogenous lipids and their respective role in cancer cell proliferation and therapeutic response to lipogenesis inhibitors is of critical importance. Here, we show that the proliferation of various cancer cell lines (PC3M, HepG2, HOP62 and T24) is attenuated when cultured in lipid-reduced conditions in a cell line-dependent manner, with PC3M being the least affected. Interestingly, all cell lines - lipogenic (PC3M, HepG2, HOP62) as well as non-lipogenic (T24) - raised their lipogenic activity in these conditions, albeit to a different degree. Cells that attained the highest lipogenic activity under these conditions were best able to cope with lipid reduction in term of proliferative capacity. Supplementation of the medium with very low density lipoproteins, free fatty acids and cholesterol reversed this activation, indicating that the mere lack of lipids is sufficient to activate de novo lipogenesis in cancer cells. Consequently, cancer cells grown in lipid-reduced conditions became more dependent on de novo lipid synthesis pathways and were more sensitive to inhibitors of lipogenic pathways, like Soraphen A and Simvastatin. Collectively, these data indicate that limitation of access to exogenous lipids, as may occur in intact tumors, activates de novo lipogenesis is cancer cells, helps them to thrive under these conditions and makes them more vulnerable to lipogenesis inhibitors. These observations have important implications for the design of new antineoplastic strategies targeting the cancer cell's lipid metabolism. PMID:25215509

  15. Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

    PubMed

    Lucidi, P; Porcellati, F; Marinelli Andreoli, A; Candeloro, P; Cioli, P; Bolli, G B; Fanelli, C G

    2017-06-06

    This study measured the insulin concentration (Ins [C] ) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). Measurements included Ins [C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. In vials of NPH(R+) (assumed to be 100%), Ins [C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively. Likewise, in pen cartridges, Ins [C] in the clear phase of NPH(R-) was<1%, but 182±33%, 204±22% and 229±62% in the cloudy phases of Novo, Lilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). Ins [C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Characteristics of De Novo Acute Myeloid Leukemia Patients in Palestine: Experience of An-Najah National University Hospital

    PubMed

    Abuhelwa, Ziad; Al Shaer, Qasem; Taha, Sari; Ayoub, Khubaib; Amer, Riad

    2017-09-27

    Objective: To describe the characteristics of de novo acute myeloid leukemia (AML) in the Palestinian population. Study design and setting: A retrospective chart review study was conducted at An-Najah National University Hospital (NNUH) during the period of January, 2014 to December, 2016. Methodology: The medical records of AML patients treated at NNUH were reviewed. All patients at least 16 years of age diagnosed with de novo AML and started on induction chemotherapy were included. Descriptive statistics were employed to analyze the data. Results: Out of 88 patients diagnosed with AML during the study period, 64 had de novo AML and were included. Median age at diagnosis was 36 years, with a male to female ratio of 1.13:1. Two thirds of the cases were from the West Bank and the remainder were from Gaza. Major complaints at presentation were fatigue (64.1%), fever (46.9%), respiratory tract infections (39.1%) and bruising (28.1%). Hepatomegaly was present in 23.4% and splenomegaly in 34.4%. At presentation, the median white blood cells (WBC) count, hemoglobin (Hb) concentration and platelet count were 30. 5x109/L, 9.3g/ dL, and 39.5 x109/L, respectively. According to the French American British (FAB) classification, M4 was the most common subtype (32.8%) followed by M3 (21.9%). After a single cycle of induction chemotherapy complete remission (CR) was seen in 26 (41.9%) and non-remission (NR) in 17 (27.4%), while 19 patients (30.6%) died during the first admission for induction. Conclusion: The characteristics of de novo AML in Palestinian patients are comparable to published data elsewhere. M4 was the most common subtype. The outcome of the first cycle of induction chemotherapy was slightly inferior to the published data for M3 patients. Further studies are warranted to identify possible causes. Creative Commons Attribution License

  17. Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy

    PubMed Central

    Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

    2015-01-01

    The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration. PMID:27081548

  18. De novo interstitial tandem duplication of chromosome 4(q21-q28)

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

    Navarro, E.G.; Ramon, F.J.H.; Jimenez, R.D.

    1996-03-29

    We describe a girl with a previously unreported de novo duplication of chromosome 4q involving segment q21-q28. Clinical manifestations included growth and psychomotor retardation, facial asymmetry, hypotelorism, epicanthic folds, mongoloid slant of palpebral fissures, apparently low-set auricles, high nasal bridge, long philtrum, small mouth, short neck, low-set thumbs, and bilateral club foot. This phenotype is compared with that of previously reported cases of duplication 4q. 12 refs., 3 figs., 1 tab.

  19. SearchGUI: A Highly Adaptable Common Interface for Proteomics Search and de Novo Engines.

    PubMed

    Barsnes, Harald; Vaudel, Marc

    2018-05-25

    Mass-spectrometry-based proteomics has become the standard approach for identifying and quantifying proteins. A vital step consists of analyzing experimentally generated mass spectra to identify the underlying peptide sequences for later mapping to the originating proteins. We here present the latest developments in SearchGUI, a common open-source interface for the most frequently used freely available proteomics search and de novo engines that has evolved into a central component in numerous bioinformatics workflows.

  20. Inhibition of Fatty Acid Synthase in Prostate Cancer by Orlistat, a Novel Therapeutic

    DTIC Science & Technology

    2007-11-01

    up large amount of proteins and lipids through their daily diet . Therefore, the levels of FAS in most tissues are low. In human tissue, FAS is...in the type and level of fats in diet and inhibition of de novo lipogenesis may hold a great promise in the prevention and treatment of cancers. Lipids...synthesis, and multiple signaling pathways. Some lipids are obtained exclusively from diet , whereas others can also be synthesized de novo. A large

  1. Early progressive encephalopathy in boys and MECP2 mutations.

    PubMed

    Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

    2006-07-11

    MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

  2. Type-I Insulin-Like Growth Factor Receptor (IGF1R)-Estrogen Receptor (ER) Crosstalk Contributes to Antiestrogen Therapy Resistance in Breast Cancer Cells

    DTIC Science & Technology

    2013-02-01

    penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR...great success in treating estrogen receptor (ER) positive breast cancer. However, both acquired and de novo resistance to this therapy prevents it from...has shown great success in treating estrogen receptor (ER) positive breast tumors. However, both acquired and de novo resistance to this therapy

  3. UM-PRS: An implementation of the procedural reasoning system for multirobot applications

    NASA Technical Reports Server (NTRS)

    Lee, Jaeho; Huber, Marcus J.; Durfee, Edmund H.; Kenny, Patrick G.

    1994-01-01

    The Procedural Reasoning System (PRS) is used in applications where predetermined situations might arise. The UM-PRS provides a reasoning system that represents robotic applications even in unpredictable domains, such as the robotic reconnaissance task domain outlined here. UM-PRS incorporates a changing context, rather than relying solely on a prearranged plan. The UM-PRS here provides representation important in the reasoning and interface between a mission plan and the executable map of an outdoor vehicle that changes its behavior based on what it comes in contact with in its environment. PRS is thus used in the dynamic control of such a vehicle, providing the basis for coordinating the joint task of multiple robotic vehicles by the their individual observations and representation.

  4. VizieR Online Data Catalog: FIR spectra of AGNs from Herschel (Fernandez-Ontiveros+, 2016)

    NASA Astrophysics Data System (ADS)

    Fernandez-Ontiveros, J. A.; Spinoglio, L.; Pereira-Santaella, M.; Malkan, M. A.; Andreani, P.; Dasyra, K. M.

    2016-11-01

    The combination of Herschel/PACS during its 3.5yr of operational life and Spitzer/IRS allows us to cover the fine-structure emission lines from the mid- to the far-IR (10-200um in the rest-frame) for all the galaxies in the sample. This database was completed with the Herschel/SPIRE published values of the [NII]205um, and [CI]371,609um line fluxes (mainly from Kamenetzky+ 2016ApJ...829...93K). Table 8 collects published mid-IR (10-35um) fine-structure line fluxes measured with Spitzer/IRS for our samples of AGN and starburst galaxies. These values were complemented with unpublished IRS observations from the Spitzer archive. (10 data files).

  5. Two low coverage bird genomes and a comparison of reference-guided versus de novo genome assemblies.

    PubMed

    Card, Daren C; Schield, Drew R; Reyes-Velasco, Jacobo; Fujita, Matthew K; Andrew, Audra L; Oyler-McCance, Sara J; Fike, Jennifer A; Tomback, Diana F; Ruggiero, Robert P; Castoe, Todd A

    2014-01-01

    As a greater number and diversity of high-quality vertebrate reference genomes become available, it is increasingly feasible to use these references to guide new draft assemblies for related species. Reference-guided assembly approaches may substantially increase the contiguity and completeness of a new genome using only low levels of genome coverage that might otherwise be insufficient for de novo genome assembly. We used low-coverage (∼3.5-5.5x) Illumina paired-end sequencing to assemble draft genomes of two bird species (the Gunnison Sage-Grouse, Centrocercus minimus, and the Clark's Nutcracker, Nucifraga columbiana). We used these data to estimate de novo genome assemblies and reference-guided assemblies, and compared the information content and completeness of these assemblies by comparing CEGMA gene set representation, repeat element content, simple sequence repeat content, and GC isochore structure among assemblies. Our results demonstrate that even lower-coverage genome sequencing projects are capable of producing informative and useful genomic resources, particularly through the use of reference-guided assemblies.

  6. Triacylglycerol synthesis in goat mammary gland. The effect of ATP, Mg2+ and glycerol 3-phosphate on the esterification of fatty acids synthesized de novo.

    PubMed Central

    Hansen, H O; Grunnet, I; Knudsen, J

    1984-01-01

    Goat mammary-gland microsomal fraction by itself induces synthesis of medium-chain-length fatty acids by goat mammary fatty acid synthetase and incorporates short- and medium-chain fatty acids into triacylglycerol. Addition of ATP in the absence or presence of Mg2+ totally inhibits triacylglycerol synthesis from short- and medium-chain fatty acids, and severely inhibits synthesis de novo of medium-chain fatty acids. The inhibition by ATP of fatty acid synthesis and triacylglycerol synthesis de novo can be relieved by glycerol 3-phosphate. The effect of ATP could not be mimicked by the non-hydrolysable ATP analogue, adenosine 5'-[beta,gamma-methylene]triphosphate and could not be shown to be caused by inhibition of the diacylglycerol acyltransferase by a phosphorylation reaction. Possible explanations for the mechanism of the inhibition by ATP are discussed, and a hypothetical model for its action is outlined. PMID:6547605

  7. ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

    DOE PAGES

    Le, Thuc M.; Poddar, Soumya; Capri, Joseph R.; ...

    2017-08-14

    It is known that leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the diseasemore » in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.« less

  8. Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development.

    PubMed

    Wang, Qiang; Li, Miaoxin; Yang, Zhenxing; Hu, Xun; Wu, Hei-Man; Ni, Peiyan; Ren, Hongyan; Deng, Wei; Li, Mingli; Ma, Xiaohong; Guo, Wanjun; Zhao, Liansheng; Wang, Yingcheng; Xiang, Bo; Lei, Wei; Sham, Pak C; Li, Tao

    2015-12-15

    Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents (N = 90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p < 9.1 × 10(-3)), and in prenatal temporal and parietal regions (Bonferroni corrected p < 0.03). Also, four prenatal anatomical subregions (VCF, MFC, OFC and ITC) have shown significant enrichment of connectedness in co-expression networks. Moreover, four genes (LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease.

  9. Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development

    PubMed Central

    Wang, Qiang; Li, Miaoxin; Yang, Zhenxing; Hu, Xun; Wu, Hei-Man; Ni, Peiyan; Ren, Hongyan; Deng, Wei; Li, Mingli; Ma, Xiaohong; Guo, Wanjun; Zhao, Liansheng; Wang, Yingcheng; Xiang, Bo; Lei, Wei; Sham, Pak C; Li, Tao

    2015-01-01

    Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents (N = 90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p < 9.1 × 10−3), and in prenatal temporal and parietal regions (Bonferroni corrected p < 0.03). Also, four prenatal anatomical subregions (VCF, MFC, OFC and ITC) have shown significant enrichment of connectedness in co-expression networks. Moreover, four genes (LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. PMID:26666178

  10. Dietary Effects on Stable Carbon Isotope Composition of Fatty Acids in Polar and Neutral Fractions of Intramuscular Fat of Lambs.

    PubMed

    van Leeuwen, Katryna A; Camin, Federica; Jerónimo, Eliana; Vasta, Valentina; Prenzler, Paul D; Ryan, Danielle; Bessa, Rui J B

    2017-11-01

    In this study we measured δ 13 C values of the main fatty acids (FA) present in neutral and polar intramuscular lipids of meat samples from 24 lambs, fed with four different diets supplemented with sunflower and linseed oil and the tanniferous shrub Cistus ladanifer L. The objective was to understand if the increase in intramuscular fat observed in lambs fed simultaneously C. ladanifer and oil was explained mostly by incorporation of diet derived FA or by increased de novo FA synthesis. De novo FA synthesis was evaluated by 13 C enrichment (‰) of 16:0 in intramuscular lipids compared to bulk diet or compared to dietary 16:0. Oil reduced 13 C enrichment of 16:0 in muscle lipid but had no effect when the diet included C. ladanifer (P value <0.01). Thus, dietary C. ladanifer blocked the inhibitory effects of lipid supplementation on de novo FA synthesis.

  11. de novo computational enzyme design.

    PubMed

    Zanghellini, Alexandre

    2014-10-01

    Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. New observations on maternal age effect on germline de novo mutations.

    PubMed

    Wong, Wendy S W; Solomon, Benjamin D; Bodian, Dale L; Kothiyal, Prachi; Eley, Greg; Huddleston, Kathi C; Baker, Robin; Thach, Dzung C; Iyer, Ramaswamy K; Vockley, Joseph G; Niederhuber, John E

    2016-01-19

    Germline mutations are the source of evolution and contribute substantially to many health-related processes. Here we use whole-genome deep sequencing data from 693 parents-offspring trios to examine the de novo point mutations (DNMs) in the offspring. Our estimate for the mutation rate per base pair per generation is 1.05 × 10(-8), well within the range of previous studies. We show that maternal age has a small but significant correlation with the total number of DNMs in the offspring after controlling for paternal age (0.51 additional mutations per year, 95% CI: 0.29, 0.73), which was not detectable in the smaller and younger parental cohorts of earlier studies. Furthermore, while the total number of DNMs increases at a constant rate for paternal age, the contribution from the mother increases at an accelerated rate with age.These observations have implications related to the incidence of de novo mutations relating to maternal age.

  13. De novo reciprocal translocation t(5;11)(q22;p15) associated with hydrops fetalis (reciprocal translocation and hydrops fetalis).

    PubMed

    Pala, Halil Gursoy; Artunc-Ulkumen, Burcu; Uyar, Yildiz; Bal, Filiz; Baytur, Yesim Bulbul; Koyuncu, Faik Mumtaz

    2015-02-01

    This is a case of a prenatally diagnosed non-immune hydrops fetalis (NIHF) associated with translocation t(5;11)(q22;p15). An association between NIHF and this translocation has not been reported previously. The patient was referred to the perinatology clinic with hydrops fetalis diagnosis at 23 weeks' gestation. We noted that the fetus had bilateral pleural effusion, ascites, widespread subcutaneous edema, membranous ventricular septal defect, hypoplastic fifth finger middle phalanx, clinodactyly, single umbilical artery. We performed cordocentesis. Chromosomal analysis on blood showed a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 11 with karyotype of 46,XX,t(5;11)(q22;p15). We present prenatal diagnosis of a de novo translocation (5;11) in a hydropic fetus with ultrason abnormalities. In our case, karyotype analysis of the fetus, mother and father provided evidence of a de novo translocation, that might explain the NIHF.

  14. Two low coverage bird genomes and a comparison of reference-guided versus de novo genome assemblies

    USGS Publications Warehouse

    Card, Daren C.; Schield, Drew R.; Reyes-Velasco, Jacobo; Fujita, Matthre K.; Andrew, Audra L.; Oyler-McCance, Sara J.; Fike, Jennifer A.; Tomback, Diana F.; Ruggiero, Robert P.; Castoe, Todd A.

    2014-01-01

    As a greater number and diversity of high-quality vertebrate reference genomes become available, it is increasingly feasible to use these references to guide new draft assemblies for related species. Reference-guided assembly approaches may substantially increase the contiguity and completeness of a new genome using only low levels of genome coverage that might otherwise be insufficient for de novo genome assembly. We used low-coverage (~3.5–5.5x) Illumina paired-end sequencing to assemble draft genomes of two bird species (the Gunnison Sage-Grouse, Centrocercus minimus, and the Clark's Nutcracker, Nucifraga columbiana). We used these data to estimate de novo genome assemblies and reference-guided assemblies, and compared the information content and completeness of these assemblies by comparing CEGMA gene set representation, repeat element content, simple sequence repeat content, and GC isochore structure among assemblies. Our results demonstrate that even lower-coverage genome sequencing projects are capable of producing informative and useful genomic resources, particularly through the use of reference-guided assemblies.

  15. [Analysis of genomic DNA methylation level in radish under cadmium stress by methylation-sensitive amplified polymorphism technique].

    PubMed

    Yang, Jin-Lan; Liu, Li-Wang; Gong, Yi-Qin; Huang, Dan-Qiong; Wang, Feng; He, Ling-Li

    2007-06-01

    The level of cytosine methylation induced by cadmium in radish (Raphanus sativus L.) genome was analysed using the technique of methylation-sensitive amplified polymorphism (MSAP). The MSAP ratios in radish seedling exposed to cadmium chloride at the concentration of 50, 250 and 500 mg/L were 37%, 43% and 51%, respectively, and the control was 34%; the full methylation levels (C(m)CGG in double strands) were at 23%, 25% and 27%, respectively, while the control was 22%. The level of increase in MSAP and full methylation indicated that de novo methylation occurred in some 5'-CCGG sites under Cd stress. There was significant positive correlation between increase of total DNA methylation level and CdCl(2) concentration. Four types of MSAP patterns: de novo methylation, de-methylation, atypical pattern and no changes of methylation pattern were identified among CdCl(2) treatments and the control. DNA methylation alteration in plants treated with CdCl(2) was mainly through de novo methylation.

  16. HALO--a Java framework for precise transcript half-life determination.

    PubMed

    Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf

    2010-05-01

    Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo.

  17. Single-molecule sequencing and chromatin conformation capture enable de novo reference assembly of the domestic goat genome.

    PubMed

    Bickhart, Derek M; Rosen, Benjamin D; Koren, Sergey; Sayre, Brian L; Hastie, Alex R; Chan, Saki; Lee, Joyce; Lam, Ernest T; Liachko, Ivan; Sullivan, Shawn T; Burton, Joshua N; Huson, Heather J; Nystrom, John C; Kelley, Christy M; Hutchison, Jana L; Zhou, Yang; Sun, Jiajie; Crisà, Alessandra; Ponce de León, F Abel; Schwartz, John C; Hammond, John A; Waldbieser, Geoffrey C; Schroeder, Steven G; Liu, George E; Dunham, Maitreya J; Shendure, Jay; Sonstegard, Tad S; Phillippy, Adam M; Van Tassell, Curtis P; Smith, Timothy P L

    2017-04-01

    The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus) based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping. These combined technologies produced what is, to our knowledge, the most continuous de novo mammalian assembly to date, with chromosome-length scaffolds and only 649 gaps. Our assembly represents a ∼400-fold improvement in continuity due to properly assembled gaps, compared to the previously published C. hircus assembly, and better resolves repetitive structures longer than 1 kb, representing the largest repeat family and immune gene complex yet produced for an individual of a ruminant species.

  18. Single-molecule sequencing and chromatin conformation capture enable de novo reference assembly of the domestic goat genome

    PubMed Central

    Bickhart, Derek M.; Rosen, Benjamin D.; Koren, Sergey; Sayre, Brian L.; Hastie, Alex R.; Chan, Saki; Lee, Joyce; Lam, Ernest T.; Liachko, Ivan; Sullivan, Shawn T.; Burton, Joshua N.; Huson, Heather J.; Nystrom, John C.; Kelley, Christy M.; Hutchison, Jana L.; Zhou, Yang; Sun, Jiajie; Crisà, Alessandra; de León, F. Abel Ponce; Schwartz, John C.; Hammond, John A.; Waldbieser, Geoffrey C.; Schroeder, Steven G.; Liu, George E.; Dunham, Maitreya J.; Shendure, Jay; Sonstegard, Tad S.; Phillippy, Adam M.; Van Tassell, Curtis P.; Smith, Timothy P.L.

    2018-01-01

    The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus), based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping. These combined technologies produced the most continuous de novo mammalian assembly to date, with chromosome-length scaffolds and only 649 gaps. Our assembly represents a ~400-fold improvement in continuity due to properly assembled gaps compared to the previously published C. hircus assembly, and better resolves repetitive structures longer than 1 kb, representing the largest repeat family and immune gene complex ever produced for an individual of a ruminant species. PMID:28263316

  19. Midgut tissue of male pine engraver , Ips pini, synthesizes monoterpenoid pheromone component ipsdienol de novo

    NASA Astrophysics Data System (ADS)

    Hall, Gregory M.; Tittiger, Claus; Andrews, Gracie L.; Mastick, Grant S.; Kuenzli, Marilyn; Luo, Xin; Seybold, Steven J.; Blomquist, Gary J.

    2002-02-01

    For over three decades the site and pathways of bark beetle aggregation pheromone production have remained elusive. Studies on pheromone production in Ips spp. bark beetles have recently shown de novo biosynthesis of pheromone components via the mevalonate pathway. The gene encoding a key regulated enzyme in this pathway, 3-hydroxy-3-methylglutaryl-CoA reductase ( HMG-R), showed high transcript levels in the anterior midgut of male pine engravers, Ips pini (Say) (Coleoptera:Scolytidae). HMG-R expression in the midgut was sex, juvenile hormone, and feeding dependent, providing strong evidence that this is the site of acyclic monoterpenoid (ipsdienol) pheromone production in male beetles. Additionally, isolated midgut tissue from fed or juvenile hormone III (JH III)-treated males converted radiolabeled acetate to ipsdienol, as assayed by radio-HPLC. These data support the de novo production of this frass-associated aggregation pheromone component by the mevalonate pathway. The induction of a metazoan HMG-R in this process does not support the postulated role of microorganisms in ipsdienol production.

  20. Data of first de-novo transcriptome assembly of a non-model species, hawksbill sea turtle, Eretmochelys imbricate, nesting of the Colombian Caribean.

    PubMed

    Hernández-Fernández, Javier

    2017-12-01

    The hawksbill sea turtle, Eretmochelys imbricata, is an endangered species of the Caribbean Colombian coast due to anthropic and natural factors that have decreased their population levels. Little is known about the genes that are involved in their immune system, sex determination, aging and others important functions. The data generated represents RNA sequencing and the first de-novo assembly of transcripts expressed in the blood of the hawksbill sea turtle. The raw FASTQ files were deposited in the NCBI SRA database with accession number SRX2653641. A total of 5.7 Gb raw sequence data were obtained, corresponding to 47,555,108 raw reads. Trinity was used to perform a first de-novo assembly, and we were able to identify 47,586 transcripts of the female hawksbill turtle transcriptome with an N50 of 1100 bp. The obtained transcriptome data will be useful for further studies of the physiology, biochemistry and evolution in this species.

  1. ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

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

    Le, Thuc M.; Poddar, Soumya; Capri, Joseph R.

    It is known that leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the diseasemore » in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.« less

  2. De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

    PubMed

    Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

    2014-06-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

  3. A girl with West syndrome and autistic features harboring a de novo TBL1XR1 mutation.

    PubMed

    Saitsu, Hirotomo; Tohyama, Jun; Walsh, Tom; Kato, Mitsuhiro; Kobayashi, Yu; Lee, Ming; Tsurusaki, Yoshinori; Miyake, Noriko; Goto, Yu-Ichi; Nishino, Ichizo; Ohtake, Akira; King, Mary-Claire; Matsumoto, Naomichi

    2014-10-01

    Recently, de novo mutations in TBL1XR1 were found in two patients with autism spectrum disorders. Here, we report on a Japanese girl presenting with West syndrome, Rett syndrome-like and autistic features. Her initial development was normal until she developed a series of spasms at 5 months of age. Electroencephalogram at 7 months showed a pattern of hypsarrhythmia, which led to a diagnosis of West syndrome. Stereotypic hand movements appeared at 8 months of age, and autistic features such as deficits in communication, hyperactivity and excitability were observed later, at 4 years and 9 months. Whole exome sequencing of the patient and her parents revealed a de novo TBL1XR1 mutation [c.209 G>A (p.Gly70Asp)] occurring at an evolutionarily conserved amino acid in an F-box-like domain. Our report expands the clinical spectrum of TBL1XR1 mutations to West syndrome with Rett-like features, together with autistic features.

  4. Damaging de novo mutations diminish motor skills in children on the autism spectrum

    PubMed Central

    Buja, Andreas; Volfovsky, Natalia; Krieger, Abba M.; Lord, Catherine; Lash, Alex E.; Wigler, Michael; Iossifov, Ivan

    2018-01-01

    In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills). PMID:29434036

  5. A Rare Case of De Novo Gigantic Ovarian Abscess within an Endometrioma

    PubMed Central

    Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

    2010-01-01

    We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one. PMID:20589187

  6. De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis.

    PubMed

    Haas, Brian J; Papanicolaou, Alexie; Yassour, Moran; Grabherr, Manfred; Blood, Philip D; Bowden, Joshua; Couger, Matthew Brian; Eccles, David; Li, Bo; Lieber, Matthias; MacManes, Matthew D; Ott, Michael; Orvis, Joshua; Pochet, Nathalie; Strozzi, Francesco; Weeks, Nathan; Westerman, Rick; William, Thomas; Dewey, Colin N; Henschel, Robert; LeDuc, Richard D; Friedman, Nir; Regev, Aviv

    2013-08-01

    De novo assembly of RNA-seq data enables researchers to study transcriptomes without the need for a genome sequence; this approach can be usefully applied, for instance, in research on 'non-model organisms' of ecological and evolutionary importance, cancer samples or the microbiome. In this protocol we describe the use of the Trinity platform for de novo transcriptome assembly from RNA-seq data in non-model organisms. We also present Trinity-supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples and approaches to identify protein-coding genes. In the procedure, we provide a workflow for genome-independent transcriptome analysis leveraging the Trinity platform. The software, documentation and demonstrations are freely available from http://trinityrnaseq.sourceforge.net. The run time of this protocol is highly dependent on the size and complexity of data to be analyzed. The example data set analyzed in the procedure detailed herein can be processed in less than 5 h.

  7. Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15.

    PubMed

    Pesz, Karolina; Pienkowski, Victor Murcia; Pollak, Agnieszka; Gasperowicz, Piotr; Sykulski, Maciej; Kosińska, Joanna; Kiszko, Magdalena; Krzykwa, Bogusława; Bartnik-Głaska, Magdalena; Nowakowska, Beata; Rydzanicz, Małgorzata; Sasiadek, Maria Małgorzata; Płoski, Rafał

    2018-04-03

    Mapping of de novo balanced chromosomal translocations (BCTs) in patients with sporadic poorly characterized disease(s) is an unbiased method of finding candidate gene(s) responsible for the observed symptoms. We present a paediatric patient suffering from epilepsy, developmental delay (DD) and atrial septal defect IIº (ASD) requiring surgery. Karyotyping indicated an apparently balanced de novo reciprocal translocation 46,XX,t(3;4)(p25.3;q31.1), whereas aCGH did not reveal any copy number changes. Using shallow mate-pair whole genome sequencing and direct Sanger sequencing of breakpoint regions we found that translocation disrupted SLC6A1 and NAA15 genes. Our results confirm two previous reports indicating that loss of function of a single allele of SLC6A1 causes epilepsy. In addition, we extend existing evidence that disruption of NAA15 is associated with DD and with congenital heart defects. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Evolution of the alternative AQP2 gene: Acquisition of a novel protein-coding sequence in dolphins.

    PubMed

    Kishida, Takushi; Suzuki, Miwa; Takayama, Asuka

    2018-01-01

    Taxon-specific de novo protein-coding sequences are thought to be important for taxon-specific environmental adaptation. A recent study revealed that bottlenose dolphins acquired a novel isoform of aquaporin 2 generated by alternative splicing (alternative AQP2), which helps dolphins to live in hyperosmotic seawater. The AQP2 gene consists of four exons, but the alternative AQP2 gene lacks the fourth exon and instead has a longer third exon that includes the original third exon and a part of the original third intron. Here, we show that the latter half of the third exon of the alternative AQP2 arose from a non-protein-coding sequence. Intact ORF of this de novo sequence is shared not by all cetaceans, but only by delphinoids. However, this sequence is conservative in all modern cetaceans, implying that this de novo sequence potentially plays important roles for marine adaptation in cetaceans. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Interphase FISH for BCR-ABL1 rearrangement on neutrophils: A decisive tool to discriminate a lymphoid blast crisis of chronic myeloid leukemia from a de novo BCR-ABL1 positive acute lymphoblastic leukemia.

    PubMed

    Balducci, Estelle; Loosveld, Marie; Rahal, Ilhem; Boudjarane, John; Alazard, Emilie; Missirian, Chantal; Lafage-Pochitaloff, Marina; Michel, Gérard; Zattara, Hélène

    2018-02-01

    Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML. This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL. Copyright © 2017 John Wiley & Sons, Ltd.

  10. De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.

    PubMed

    Eichenberger, Michael; Hansson, Anders; Fischer, David; Dürr, Lara; Naesby, Michael

    2018-06-01

    Anthocyanins (ACNs) are plant secondary metabolites responsible for most of the red, purple and blue colors of flowers, fruits and vegetables. They are increasingly used in the food and beverage industry as natural alternative to artificial colorants. Production of these compounds by fermentation of microorganisms would provide an attractive alternative. In this study, Saccharomyces cerevisiae was engineered for de novo production of the three basic anthocyanins, as well as the three main trans-flavan-3-ols. Enzymes from different plant sources were screened and efficient variants found for most steps of the biosynthetic pathway. However, the anthocyanidin synthase was identified as a major obstacle to efficient production. In yeast, this enzyme converts the majority of its natural substrates leucoanthocyanidins into the off-pathway flavonols. Nonetheless, de novo biosynthesis of ACNs was shown for the first time in yeast and for the first time in a single microorganism. It provides a framework for optimizing the activity of anthocyanidin synthase and represents an important step towards sustainable industrial production of these highly relevant molecules in yeast.

  11. An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

    PubMed

    Werling, Donna M; Brand, Harrison; An, Joon-Yong; Stone, Matthew R; Zhu, Lingxue; Glessner, Joseph T; Collins, Ryan L; Dong, Shan; Layer, Ryan M; Markenscoff-Papadimitriou, Eirene; Farrell, Andrew; Schwartz, Grace B; Wang, Harold Z; Currall, Benjamin B; Zhao, Xuefang; Dea, Jeanselle; Duhn, Clif; Erdman, Carolyn A; Gilson, Michael C; Yadav, Rachita; Handsaker, Robert E; Kashin, Seva; Klei, Lambertus; Mandell, Jeffrey D; Nowakowski, Tomasz J; Liu, Yuwen; Pochareddy, Sirisha; Smith, Louw; Walker, Michael F; Waterman, Matthew J; He, Xin; Kriegstein, Arnold R; Rubenstein, John L; Sestan, Nenad; McCarroll, Steven A; Neale, Benjamin M; Coon, Hilary; Willsey, A Jeremy; Buxbaum, Joseph D; Daly, Mark J; State, Matthew W; Quinlan, Aaron R; Marth, Gabor T; Roeder, Kathryn; Devlin, Bernie; Talkowski, Michael E; Sanders, Stephan J

    2018-05-01

    Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutations, coding regions still exhibited the strongest associations. Thus, in autism, the contribution of de novo noncoding variation is probably modest in comparison to that of de novo coding variants. Robust results from future WGS studies will require large cohorts and comprehensive analytical strategies that consider the substantial multiple-testing burden.

  12. Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.

    PubMed

    Takata, Atsushi; Miyake, Noriko; Tsurusaki, Yoshinori; Fukai, Ryoko; Miyatake, Satoko; Koshimizu, Eriko; Kushima, Itaru; Okada, Takashi; Morikawa, Mako; Uno, Yota; Ishizuka, Kanako; Nakamura, Kazuhiko; Tsujii, Masatsugu; Yoshikawa, Takeo; Toyota, Tomoko; Okamoto, Nobuhiko; Hiraki, Yoko; Hashimoto, Ryota; Yasuda, Yuka; Saitoh, Shinji; Ohashi, Kei; Sakai, Yasunari; Ohga, Shouichi; Hara, Toshiro; Kato, Mitsuhiro; Nakamura, Kazuyuki; Ito, Aiko; Seiwa, Chizuru; Shirahata, Emi; Osaka, Hitoshi; Matsumoto, Ayumi; Takeshita, Saoko; Tohyama, Jun; Saikusa, Tomoko; Matsuishi, Toyojiro; Nakamura, Takumi; Tsuboi, Takashi; Kato, Tadafumi; Suzuki, Toshifumi; Saitsu, Hirotomo; Nakashima, Mitsuko; Mizuguchi, Takeshi; Tanaka, Fumiaki; Mori, Norio; Ozaki, Norio; Matsumoto, Naomichi

    2018-01-16

    Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A rare case of de novo gigantic ovarian abscess within an endometrioma.

    PubMed

    Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

    2010-06-01

    We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one.

  14. De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal Correctional Clients.

    PubMed

    DeLisi, Matt; Tahja, Katherine N; Drury, Alan J; Elbert, Michael J; Caropreso, Daniel E; Heinrichs, Timothy

    2018-01-01

    Adult antisocial behavior is almost always predated by delinquency during childhood or adolescence; however, there is also evidence of adult-onset criminal offending. This study examined this controversial subgroup of offenders using self-reported and official data from a total population of federal correctional clients selected from the Midwestern United States. Difference of means t-tests, chi-square tests, and logistic regression models found that 11.7% of clients had an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring at age 60 years or older. This group-introduced as de novo advanced adult-onset offenders-had high socioeconomic status, mixed evidence of adverse childhood experiences, and virtually no usage of drugs with the exception of alcohol. These offenders were primarily convicted of social security and white-collar crimes and evinced remarkably low psychopathology and criminal risk. More research is needed to replicate the phenomenon of de novo advanced adult-onset offending. © 2017 American Academy of Forensic Sciences.

  15. Damaging de novo mutations diminish motor skills in children on the autism spectrum.

    PubMed

    Buja, Andreas; Volfovsky, Natalia; Krieger, Abba M; Lord, Catherine; Lash, Alex E; Wigler, Michael; Iossifov, Ivan

    2018-02-20

    In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills). Copyright © 2018 the Author(s). Published by PNAS.

  16. Monitoring the Near-infrared Volcanic Flux from Io's Jupiter-facing Hemisphere from Fan Mountain Observatory

    NASA Astrophysics Data System (ADS)

    Skrutskie, Michael F.; Nelson, Matthew J.; Schmidt, Carl

    2016-10-01

    Fan Mountain Observatory, near Charlottesville, Virginia, is a dark-sky site that supports a number of telescopes including a 31-inch reflecting telescope equipped with a 1024x1024 HgCdTe 1-2.5 um (YJHK) imager. Reflected sunlight ordinarily overwhelms Io's comparatively weak K-band (2.0-2.4 um) volcanic emission in unresolved observations, however when Io is eclipsed in Jupiter's shadow even a small infrared-equipped telescope can detect Io's volcanic emission. The Fan Mountain Infrared Camera observed Io in eclipse at regular intervals, typically weekly, during the few months before and after Jupiter's March 2016 opposition. When in eclipse Io's Jupiter-facing hemisphere is oriented toward Earth with sub-Earth longitudes at the time of observation ranging from 345 - 360 degrees (pre-opposition) to 0 - 15 degrees (post-opposition). A K-band filter (2.04-2.42 um) provided a bulk measurement of Io's volcanic flux weighted largely toward the 2.4 um end of this filter given the typical 500K color temperature of the volcanic emission. Most epochs also included observation in a narrowband filter centered at 2.12 um that, when combined with the broadband "long" wavelength measurement, provided a proxy for color temperature. The K-band flux of Io varied by more than 2 magnitudes during the 7 month observation interval. The [2.12 um - K-band] color of the emission strongly correlated with the K-band flux in the expected sense that the color temperature of the emission increased when Io's broadband volcanic flux was the greatest. One epoch of TripleSpec near-IR Io eclipse spectroscopy (0.90 - 2.45 um; R~3000) from the Apache Point Observatory 3.5-meter telescope provided ground truth for transforming the filter photometry into quantitative temperatures.

  17. Genome analysis of Daldinia eschscholtzii strains UM 1400 and UM 1020, wood-decaying fungi isolated from human hosts

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

    Chan, Chai Ling; Yew, Su Mei; Ngeow, Yun Fong

    Background: Daldinia eschscholtzii is a wood-inhabiting fungus that causes wood decay under certain conditions. It has a broad host range and produces a large repertoire of potentially bioactive compounds. However, there is no extensive genome analysis on this fungal species. Results: Two fungal isolates (UM 1400 and UM 1020) from human specimens were identified as Daldinia eschscholtzii by morphological features and ITS-based phylogenetic analysis. Both genomes were similar in size with 10,822 predicted genes in UM 1400 (35.8 Mb) and 11,120 predicted genes in UM 1020 (35.5 Mb). A total of 751 gene families were shared among both UM isolates,more » including gene families associated with fungus-host interactions. In the CAZyme comparative analysis, both genomes were found to contain arrays of CAZyme related to plant cell wall degradation. Genes encoding secreted peptidases were found in the genomes, which encode for the peptidases involved in the degradation of structural proteins in plant cell wall. In addition, arrays of secondary metabolite backbone genes were identified in both genomes, indicating of their potential to produce bioactive secondary metabolites. Both genomes also contained an abundance of gene encoding signaling components, with three proposed MAPK cascades involved in cell wall integrity, osmoregulation, and mating/filamentation. Besides genomic evidence for degrading capability, both isolates also harbored an array of genes encoding stress response proteins that are potentially significant for adaptation to living in the hostile environments. In conclusion: Our genomic studies provide further information for the biological understanding of the D. eschscholtzii and suggest that these wood-decaying fungi are also equipped for adaptation to adverse environments in the human host.« less

  18. Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

    PubMed Central

    Fox, D A; Millard, J A; Kan, L; Zeldes, W S; Davis, W; Higgs, J; Emmrich, F; Kinne, R W

    1990-01-01

    Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. Images PMID:2212003

  19. Mental health problems of undocumented migrants (UMs) in the Netherlands: a qualitative exploration of help-seeking behaviour and experiences with primary care

    PubMed Central

    Teunissen, Erik; Sherally, Jamilah; van den Muijsenbergh, Maria; Dowrick, Chris; van Weel-Baumgarten, Evelyn; van Weel, Chris

    2014-01-01

    Objective To explore health-seeking behaviour and experiences of undocumented migrants (UMs) in general practice in relation to mental health problems. Design Qualitative study using semistructured interviews and thematic analysis. Participants 15 UMs in the Netherlands, varying in age, gender, country of origin and education; inclusion until theoretical saturation was reached. Setting 4 cities in the Netherlands. Results UMs consider mental health problems to be directly related to their precarious living conditions. For support, they refer to friends and religion first, the general practitioner (GP) is their last resort. Barriers for seeking help include taboo on mental health problems, lack of knowledge of and trust in GPs competencies regarding mental health and general barriers in accessing healthcare as an UM (lack of knowledge of the right to access healthcare, fear of prosecution, financial constraints and practical difficulties). Once access has been gained, satisfaction with care is high. This is primarily due to the attitude of the GPs and the effectiveness of the treatment. Reasons for dissatisfaction with GP care are an experienced lack of time, lack of personal attention and absence of physical examination. Expectations of the GP vary, medication for mental health problems is not necessarily seen as a good practice. Conclusions UMs often see their precarious living conditions as an important determinant of their mental health; they do not easily seek help for mental health problems and various barriers hamper access to healthcare for them. Rather than for medication, UMs are looking for encouragement and support from their GP. We recommend that barriers experienced in seeking professional care are tackled at an institutional level as well as at the level of GP. PMID:25416057

  20. Comparison of gene delivery techniques for therapeutic angiogenesis ultrasound-mediated destruction of carrier microbubbles versus direct intramuscular injection.

    PubMed

    Kobulnik, Jeremy; Kuliszewski, Michael A; Stewart, Duncan J; Lindner, Jonathan R; Leong-Poi, Howard

    2009-10-27

    This study was designed to compare the efficacy of angiogenic gene delivery by ultrasound-mediated (UM) destruction of intravenous carrier microbubbles to direct intramuscular (IM) injections. Current trials of gene therapy for angiogenesis remain limited by suboptimal, invasive delivery techniques. Hind-limb ischemia was produced by iliac artery ligation in 99 rats. In 32 rats, UM delivery of green fluorescent protein (GFP)/vascular endothelial growth factor-165 (VEGF(165)) plasmid deoxyribonucleic acid was performed. Thirty-five animals received IM injections of VEGF(165)/GFP plasmid. Remaining rats received no treatment. Before delivery (day 14 after ligation) and at days 17, 21, and 28 and week 8 after ligation, microvascular blood volume and microvascular blood flow to the proximal hind limbs were assessed by contrast-enhanced ultrasound (n = 8 per group). Total transfection was assessed by reverse transcriptase-polymerase chain reaction, and localization of transfection was determined by immunohistochemistry. By day 28, both IM and UM delivery of VEGF(165) produced significant increases in microvascular blood volume and microvascular blood flow. Whereas increases in microvascular blood volume were similar between treatment groups, microvascular blood flow was greater (p < 0.005) in UM-treated animals as compared with IM-treated animals, persisting to week 8. The VEGF(165)/GFP messenger ribonucleic acid expression was greater (p < 0.05) for IM-treated animals. A strong GFP signal was detected for both groups and was localized to focal perivascular regions and myocytes around injection sites for IM and to the vascular endothelium of arterioles/capillaries in a wider distribution for UM delivery. Despite lower transfection levels, UM delivery of VEGF(165) is as effective as IM injections. The UM delivery results in directed vascular transfection over a wider distribution, which may account for the more efficient angiogenesis.

  1. Mental health problems of undocumented migrants in the Netherlands: A qualitative exploration of recognition, recording, and treatment by general practitioners.

    PubMed

    Teunissen, Erik; Van Bavel, Eric; Van Den Driessen Mareeuw, Francine; Macfarlane, Anne; Van Weel-Baumgarten, Evelyn; Van Den Muijsenbergh, Maria; Van Weel, Chris

    2015-06-01

    To explore the views and experiences of general practitioners (GPs) in relation to recognition, recording, and treatment of mental health problems of undocumented migrants (UMs), and to gain insight in the reasons for under-registration of mental health problems in the electronic medical records. Qualitative study design with semi-structured interviews using a topic guide. Sixteen GPs in the Netherlands with clinical expertise in the care of UMs. GPs recognized many mental health problems in UMs. Barriers that prevented them from recording these problems and from delivering appropriate care were their low consultation rates, physical presentation of mental health problems, high number of other problems, the UM's lack of trust towards health care professionals, and cultural differences in health beliefs and language barriers. Referrals to mental health care organizations were often seen as problematic by GPs. To overcome these barriers, GPs provided personalized care as far as possible, referred to other primary care professionals such as social workers or mental health care nurses in their practice, and were a little less restrictive in prescribing psychotropics than guidelines recommended. GPs experienced a variety of barriers in engaging with UMs when identifying or suspecting mental health problems. This explains why there is a gap between the high recognition of mental health problems and the low recording of these problems in general practice files. It is recommended that GPs address mental health problems more actively, strive for continuity of care in order to gain trust of the UMs, and look for opportunities to provide mental care that is accessible and acceptable for UMs.

  2. Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO.

    PubMed

    Di Paola, Rosanna; Cordaro, Marika; Crupi, Rosalia; Siracusa, Rosalba; Campolo, Michela; Bruschetta, Giuseppe; Fusco, Roberta; Pugliatti, Pietro; Esposito, Emanuela; Cuzzocrea, Salvatore

    2016-08-01

    Myocardial infarction is the leading cause of death, occurs after prolonged ischemia of the coronary arteries. Restore blood flow is the first intervention help against heart attack. However, reperfusion of the arteries leads to ischemia/reperfusion injury (I/R). The fatty acid amide palmitoylethanolamide (PEA) is an endogenous compound widely present in living organisms, with analgesic and anti-inflammatory properties. The present study evaluated the effect of ultramicronized palmitoylethanolamide (PEA-um) treatment on the inflammatory process associated with myocardial I/R. Myocardial ischemia reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-um, was administered (10 mg/kg) 15 min after ischemia and 1 h after reperfusion. In this study, we demonstrated that PEA-um treatment reduces myocardial tissue injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin) expression, proinflammatory cytokines (TNF-α, IL-1β) production, nitrotyrosine and PAR formation, nuclear factor kB expression, and apoptosis (Fas-L, Bcl-2) activation. In addition to study whether the protective effect of PEA-um on myocardial ischemia reperfusion injury is also related to the activation of PPAR-α, in a separate set of experiments it has been performed myocardial I/R in PPARα mice. Genetic ablation of peroxisome proliferator activated receptor (PPAR)-α in PPAR-αKO mice exacerbated Myocardial ischemia reperfusion injury when compared with PPAR-αWT mice. PEA-um induced cardioprotection in PPAR-α wild-type mice, but the same effect cannot be observed in PPAR-αKO mice. Our results have clearly shown a modulation of the inflammatory process, associated with myocardial ischemia reperfusion injury, following administration of PEA-um.

  3. Contralateral prophylactic mastectomy rate stable at major Canadian breast cancer center.

    PubMed

    Roberts, Amanda; Sandhu, Lakhbir; Cil, Tulin D; Hofer, Stefan O P; Zhong, Toni

    2016-06-10

    To examine trends of contralateral prophylactic mastectomy (CPM) rates at a Canadian academic breast cancer center. A single-institution retrospective cohort study was completed. Women of any age who underwent at least a unilateral mastectomy (UM) for primary unilateral breast carcinoma between January 1, 2004 and December 31, 2010 were included. Patients who underwent CPM on the same day as UM were isolated to create two distinct cohorts. Patient and procedure characteristics were compared across groups using R software (version 3.1.0). The percentage of CPMs per year was determined. The Cochrane-Armitage test was used to assess the trend of CPMs over time. A P value of < 0.05 was considered significant. A total of 811 women met the inclusions/exclusion criteria; 759 (93.6%) underwent UM alone and 52 (6.4%) underwent UM with immediate CPM. The absolute number of procedures (UM and UM + CPM) increased over time, from 83 in 2004 to 147 in 2010 reflecting an increase in mastectomy volume. Annual CPM rates did not increase over time (P = 0.7) and varied between 2.6% to 10.7%. Family history of breast cancer [OR 3.6 (1.8-7.3)] and immediate reconstruction [10.0 (5.2-19.3)] were both significantly associated with CPM. Women who underwent CPM were younger (median age CPM 49 years vs UM 52 years, P < 0.0001) but age less than 50 years was not statistically associated with increased rates of CPM. CPM rates from 2004 to 2010 at a high-volume Canadian breast cancer center did not increase over time, in contrast to trends observed in the United States.

  4. First Asteroid Spectrometric Observations with BTA: 3045 Alois

    NASA Astrophysics Data System (ADS)

    Busarev, V. V.; Burenkov, A. N.; Pramskij, A. G.

    2001-11-01

    BTA, Russian 6-m telescope, was mainly used for faint stars and extragalactic objects observations. We have firstly performed with the telescope spectrometric observations of a main belt asteroid, 3045 Alois, and are planning to use it for Centaurs and Kuiper Belt objects spectrometry. We have obtained some results of the observations. Spectra of Alois were recorded on two nights of March 2001 (29/30 and 30/31) with a long slit spectrograph (UAGS + CCD) in the .38-.80 um spectral range. HD105633 (G5) [1] considered as a solar analog was also observed, and the data were used for calculation the asteroid reflectance spectra. It was found that reflectance spectra of Alois obtained on different nights have various continuum slopes and absorption features. The reflectance spectrum on 29/30 March had a flat continuum in the range .44-.65 um and absorption bands at .5 um (ab. 7 % with respect to the continuum) similar to that found on the E-type asteroid 2035 Stearns [2], and at .80 um (ab. 25 %). Another one on 30/31 March had a red continuum in the range .40-.67 um and absorption bands at .43 um (ab. 6 %) resembling absorption features found on some C-, M- and S-type asteroids [3, 4], and at .80 um (ab. 17 %). From the data and taking into account the mean heliocentric distance of 3045 Alois (3.13 AU) we suppose that the asteroid having irregular spectral characteristics may be of M- or E-type and possibly hydrated. Unfortunately, its albedo and rotational period remain still unknown. [1] Mermilliod J.-C. (1994) Bull. Inf. CDS 45, 3. [2] Fornasier S. and Lazzarine M. (2001) Icarus 152, 127-133. [3] Vilas F. et al. (1993) Icarus 102, 225-231. [4] Busarev V. V. (2001) LPSC XXXII, abs. 1927.

  5. Genome analysis of Daldinia eschscholtzii strains UM 1400 and UM 1020, wood-decaying fungi isolated from human hosts

    DOE PAGES

    Chan, Chai Ling; Yew, Su Mei; Ngeow, Yun Fong; ...

    2015-11-18

    Background: Daldinia eschscholtzii is a wood-inhabiting fungus that causes wood decay under certain conditions. It has a broad host range and produces a large repertoire of potentially bioactive compounds. However, there is no extensive genome analysis on this fungal species. Results: Two fungal isolates (UM 1400 and UM 1020) from human specimens were identified as Daldinia eschscholtzii by morphological features and ITS-based phylogenetic analysis. Both genomes were similar in size with 10,822 predicted genes in UM 1400 (35.8 Mb) and 11,120 predicted genes in UM 1020 (35.5 Mb). A total of 751 gene families were shared among both UM isolates,more » including gene families associated with fungus-host interactions. In the CAZyme comparative analysis, both genomes were found to contain arrays of CAZyme related to plant cell wall degradation. Genes encoding secreted peptidases were found in the genomes, which encode for the peptidases involved in the degradation of structural proteins in plant cell wall. In addition, arrays of secondary metabolite backbone genes were identified in both genomes, indicating of their potential to produce bioactive secondary metabolites. Both genomes also contained an abundance of gene encoding signaling components, with three proposed MAPK cascades involved in cell wall integrity, osmoregulation, and mating/filamentation. Besides genomic evidence for degrading capability, both isolates also harbored an array of genes encoding stress response proteins that are potentially significant for adaptation to living in the hostile environments. In conclusion: Our genomic studies provide further information for the biological understanding of the D. eschscholtzii and suggest that these wood-decaying fungi are also equipped for adaptation to adverse environments in the human host.« less

  6. Aircraft Natural/Artificial Icing

    DTIC Science & Technology

    2009-02-12

    LWC are 0.1 to 0.8 g/m3 for stratiform clouds and 0.2 to 2.5 g/m3 for cumuliform clouds. The drop size distribution in the cloud is usually...cloud hydrometeor size distributions from 0.5 to 50 um, particle shape (discrimination between water and ice), particle optical properties (refractive...index), precipitation size distributions from 25 um to 1550 um, liquid water content from 0.01 to 3 gm-3 and aircraft velocity and atmospheric

  7. Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

    DTIC Science & Technology

    2013-09-01

    proliferation using this protocol as reported or with any modifications tested Medium Y27632 (uM) Hydrocortisone (ug/mL) Insulin (ug/mL) rhEGF...0 + + 0 + + 0 + 0 Medium Y27632 (uM) Hydrocortisone (ug/mL) Insulin (ug/mL) rhEGF (ng/mL) Adenine (ug/mL) Result...reported (1) except for cholera toxin, which was toxic to this tumor under these conditions 17 Medium Y27632 (uM) Hydrocortisone (ug/mL

  8. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.

    PubMed

    Ambrosini, Grazia; Sawle, Ashley D; Musi, Elgilda; Schwartz, Gary K

    2015-10-20

    Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth.Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations.

  9. Unsaponifiable matter from oil of green coffee beans: cosmetic properties and safety evaluation.

    PubMed

    Wagemaker, Tais A L; Campos, Patrícia M B G Maia; Fernandes, Ana Sofia; Rijo, Patrícia; Nicolai, Marisa; Roberto, Amílcar; Rosado, Catarina; Reis, Catarina; Rodrigues, Luis M; Carvalho, Cássia Regina Limonta; Maia, Nilson Borlina; Guerreiro Filho, Oliveiro

    2016-10-01

    Unsaponifiable matter (UM), a fraction of green coffee oil (GCO) contains functional compounds responsible for desirable cosmetic properties such as UV-B absorption. To evaluate oil content and sun protection factor (SPF) variability of the two most important species of coffee and, the toxic and cytotoxic effects, as well as cosmetic properties, including antioxidant and antimicrobial activities of UM obtained from green Coffea arabica seed oil. The safety and potential cosmetic properties of UM extracted from green coffee oil (GCO) were evaluated by the brine shrimp viability and the MTT cytotoxicity assays. The SPF and antioxidant activity were evaluated using in vitro methods. Relevant cytotoxicity was found against keratinocytes for concentrations ≥25 µg/mL and in the brine shrimp assay (LC50 24 µg/mL). Antimicrobial and antioxidant activities (IC50 1448 µg/mL) were low in UM but SPF was 10 times higher than in GCO. UM is a novel potential UV-B absorbent but its use as a cosmetic ingredient should be better considered due to the considerable cytotoxicity shown in the experimental conditions described.

  10. Medusa consumption and prey selection of silver pomfret Pampus argenteus juveniles

    NASA Astrophysics Data System (ADS)

    Liu, Chunsheng; Zhuang, Zhimeng; Chen, Siqing; Shi, Zhaohong; Yan, Jingping; Liu, Changlin

    2014-01-01

    The current study explored Aurelia aurita and Rhopilema esculent um consumption by silver pomfret juveniles, as well as their prey selection between the two jellyfish species. Silver pomfret juveniles weighing 1±0.1 g actively preyed on both the species. Their daily A. aurita consumption was 11.6 times their own body weights regardless of the size of A. aurita medusae. Their daily R. esculent um consumption was 13, 9.1, 5, and 4.1 times their own body weights when the R. esculentum medusae were 10, 20, 30, and 40 mm in bell diameter, respectively. The survival rates of the R. esculent um were higher than those of the A. aurita. When the R. esculent um medusae were more than 30 mm in bell diameter, their survival rate exceeded 92%. Silver pomfrets serve as a type of potential predators on A. aurita in coastal waters, and they have little influence on R. esculent um with a size exceeding 30 mm. Besides, A. aurita may be able to be used as fish prey in silver pomfret artificial breeding.

  11. Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting

    PubMed Central

    Bhoo-Pathy, Nirmala; Verkooijen, Helena Marieke; Tan, Ern-Yu; Miao, Hui; Taib, Nur Aishah Mohd; Brand, Judith S.; Dent, Rebecca A.; See, Mee-Hoong; Subramaniam, ShriDevi; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har

    2015-01-01

    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient’s demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996–2000, 2001–2005 and 2006–2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996–2000, 7% in 2001–2005, and 9% in 2006–2010. Patients in 2006–2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%–28·2%), 28·8% (95% CI: 23·4%–34·2%), and 33·6% (95% CI: 28·8%–38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study. PMID:26536962

  12. GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT.

    PubMed

    Schünemann, Holger J; Wiercioch, Wojtek; Brozek, Jan; Etxeandia-Ikobaltzeta, Itziar; Mustafa, Reem A; Manja, Veena; Brignardello-Petersen, Romina; Neumann, Ignacio; Falavigna, Maicon; Alhazzani, Waleed; Santesso, Nancy; Zhang, Yuan; Meerpohl, Jörg J; Morgan, Rebecca L; Rochwerg, Bram; Darzi, Andrea; Rojas, Maria Ximenas; Carrasco-Labra, Alonso; Adi, Yaser; AlRayees, Zulfa; Riva, John; Bollig, Claudia; Moore, Ainsley; Yepes-Nuñez, Juan José; Cuello, Carlos; Waziry, Reem; Akl, Elie A

    2017-01-01

    Guideline developers can: (1) adopt existing recommendations from others; (2) adapt existing recommendations to their own context; or (3) create recommendations de novo. Monetary and nonmonetary resources, credibility, maximization of uptake, as well as logical arguments should guide the choice of the approach and processes. To describe a potentially efficient model for guideline production based on adoption, adaptation, and/or de novo development of recommendations utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks. We applied the model in a new national guideline program producing 22 practice guidelines. We searched for relevant evidence that informs the direction and strength of a recommendation. We then produced GRADE EtDs for guideline panels to develop recommendations. We produced a total of 80 EtD frameworks in approximately 4 months and 146 EtDs in approximately 6 months in two waves. Use of the EtD frameworks allowed panel members understand judgments of others about the criteria that bear on guideline recommendations and then make their own judgments about those criteria in a systematic approach. The "GRADE-ADOLOPMENT" approach to guideline production combines adoption, adaptation, and, as needed, de novo development of recommendations. If developers of guidelines follow EtD criteria more widely and make their work publically available, this approach should prove even more useful. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Impact of heat stress on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species

    NASA Astrophysics Data System (ADS)

    Kleist, E.; Mentel, T. F.; Andres, S.; Bohne, A.; Folkers, A.; Kiendler-Scharr, A.; Rudich, Y.; Springer, M.; Tillmann, R.; Wildt, J.

    2012-07-01

    Changes in the biogenic volatile organic compound (BVOC) emissions from European beech, Palestine oak, Scots pine, and Norway spruce exposed to heat stress were measured in a laboratory setup. In general, heat stress decreased the de novo emissions of monoterpenes, sesquiterpenes and phenolic BVOC. Decreasing emission strength with heat stress was independent of the tree species and whether the de novo emissions being constitutive or induced by biotic stress. In contrast, heat stress induced emissions of green leaf volatiles. It also amplified the release of monoterpenes stored in resin ducts of conifers probably due to heat-induced damage of these resin ducts. The increased release of monoterpenes could be strong and long lasting. But, despite of such strong monoterpene emission pulses, the net effect of heat stress on BVOC emissions from conifers can be an overall decrease. In particular during insect attack on conifers the plants showed de novo emissions of sesquiterpenes and phenolic BVOC which exceeded constitutive monoterpene emissions from pools. The heat stress induced decrease of these de novo emissions was larger than the increased release caused by damage of resin ducts. We project that global change induced heat waves may cause increased BVOC emissions only in cases where the respective areas are predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOC. Otherwise the overall effect of heat stress will be a decrease in BVOC emissions.

  14. Building a Better Fragment Library for De Novo Protein Structure Prediction

    PubMed Central

    de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

    2015-01-01

    Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

  15. Tiled Microarray Identification of Novel Viral Transcript Structures and Distinct Transcriptional Profiles during Two Modes of Productive Murine Gammaherpesvirus 68 Infection

    PubMed Central

    Cheng, Benson Yee Hin; Zhi, Jizu; Santana, Alexis; Khan, Sohail; Salinas, Eduardo; Forrest, J. Craig; Zheng, Yueting; Jaggi, Shirin; Leatherwood, Janet

    2012-01-01

    We applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in a time course of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently infected B cell line. During de novo infection, all open reading frames (ORFs) were transcribed and clustered into four major temporal groups that were overlapping yet distinct from clusters based on the phorbol ester-stimulated B cell reactivation time course. High-density transcript analysis at 2-h intervals during de novo infection mapped gene boundaries with a 20-nucleotide resolution, including a previously undefined ORF73 transcript and the MHV68 ORF63 homolog of Kaposi's sarcoma-associated herpesvirus vNLRP1. ORF6 transcript initiation was mapped by tiled array and confirmed by 5′ rapid amplification of cDNA ends. The ∼1.3-kb region upstream of ORF6 was responsive to lytic infection and MHV68 RTA, identifying a novel RTA-responsive promoter. Transcription in intergenic regions consistent with the previously defined expressed genomic regions was detected during both types of productive infection. We conclude that the MHV68 transcriptome is dynamic and distinct during de novo fibroblast infection and upon phorbol ester-stimulated B cell reactivation, highlighting the need to evaluate further transcript structure and the context-dependent molecular events that govern viral gene expression during chronic infection. PMID:22318145

  16. Activation of Nrf2 by H2O2: de novo synthesis versus nuclear translocation.

    PubMed

    Covas, Gonçalo; Marinho, H Susana; Cyrne, Luísa; Antunes, Fernando

    2013-01-01

    The most common mechanism described for the activation of the transcription factor Nrf2 is based on the inhibition of its degradation in the cytosol followed by its translocation to the nucleus. Recently, Nrf2 de novo synthesis was proposed as an additional mechanism for the rapid upregulation of Nrf2 by hydrogen peroxide (H2O2). Here, we describe a detailed protocol, including solutions, pilot experiments, and experimental setups, which allows exploring the role of H2O2, delivered either as a bolus or as a steady state, in endogenous Nrf2 translocation and synthesis. We also show experimental data, illustrating that H2O2 effects on Nrf2 activation in HeLa cells are strongly dependent both on the H2O2 concentration and on the method of H2O2 delivery. The de novo synthesis of Nrf2 is triggered within 5min of exposure to low concentrations of H2O2, preceding Nrf2 translocation to the nucleus which is slower. Evidence of de novo synthesis of Nrf2 is observed only for low H2O2 steady-state concentrations, a condition that is prevalent in vivo. This study illustrates the applicability of the steady-state delivery of H2O2 to uncover subtle regulatory effects elicited by H2O2 in narrow concentration and time ranges. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    PubMed

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p<0.001), but not 6days post-prime. Following a boost challenge, these memory CD8+ T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p>0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

    PubMed

    Zago, Alexandre C; Matte, Bruno S; Reginato, Luciana; Iturry-Yamamoto, Germán; Krepsky, Ana; Bergoli, Luiz Carlos C; Balvedi, Julise; Raudales, José C; Saadi, Eduardo K; Zago, Alcides J

    2012-01-01

    Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

  19. Functional characterization of the first filamentous fungal tRNA-isopentenyltransferase and its role in the virulence of Claviceps purpurea.

    PubMed

    Hinsch, Janine; Galuszka, Petr; Tudzynski, Paul

    2016-08-01

    In plants, cytokinins (CKs) are synthesized de novo or by the degradation of modified tRNAs. Recently, the first fungal de novo pathway was identified within the plant pathogen Claviceps purpurea. As the deletion of the de novo pathway did not lead to a complete loss of CKs, this work focuses on the tRNA-modifying protein tRNA-isopentenyltransferase (CptRNA-IPT). The contribution of this enzyme to the CK pool of Claviceps and the role of CKs in the host-pathogen interaction are emphasized. The effects of the deletion of cptRNA-ipt and the double deletion of cptRNA-ipt and the key gene of de novo biosynthesis cpipt-log on growth, CK biosynthesis and virulence were analyzed. In addition, the sites of action of CptRNA-IPT were visualized using reporter gene fusions. In addition to CK-independent functions, CptRNA-IPT was essential for the biosynthesis of cis-zeatin (cZ) and contributed to the formation of isopentenyladenine (iP) and trans-zeatin (tZ). Although ΔcptRNA-ipt was reduced in virulence, the 'CK-free' double deletion mutant was nearly apathogenic. The results prove a redundancy of the CK biosynthesis pathway in C. purpurea for iP and tZ formation. Moreover, we show, for the first time, that CKs are required for the successful establishment of a host-fungus interaction. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  20. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

    PubMed

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

    2014-12-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. Copyright© Ferrata Storti Foundation.

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