Efectos del material particulado (PM) sobre la salud y el medioambiente

EPA Pesticide Factsheets

El tamaño de las partículas se encuentra directamente vinculado con el potencial para provocar problemas de salud. La exposición a estas partículas puede afectar tanto a los pulmones como al corazón. También afectan el medioambiente.

Analisis de Alteraciones EN la Imagen Debidas a Descolimacion de un Telescopio

NASA Astrophysics Data System (ADS)

Cobos, F. J.; Galan, M. J.

1987-05-01

Podemos considerar, en términos generales, que los espejos de un telescopio tienen una calidad óptica intrínseca, entendiendo por ésta la que se ha obtenido como resultado, fundamentalmente, de la destreza del personal del Taller Optico, que considerará terminadas las superficies ópticas cuando éstas satisfagan los requisitos de diseño y las pruebas de evaluación pertinentes. Debemos esperar que, una vez instalados los espejos en el telescopio, no se altere esta calidad de la óptica por un funcionamiento inadecuado de partes mecánicas del mismo. En los últimos años, en la medida que los problemas de infraestructuratura de nuestros Observatorios se han ido resolviendo, se ha hecho más patente la necesidad de llevar a la instrumentación existente al máximo de su potencial y parte esencial de ésta la conforman los mismos te lescopios. Mejorar la calidad óptica de las imágenes obtenidas con ellos ha hecho que sea prioritario el realizar una investigación más sistemática de sus características. Este trabajo ha tenido como objetivo primordial el usar un programa de diseño óptico, en el caso particular del telescopio UNAM212, con el fin de calcular y obtener gráficamente los diagramas de manchas de imagenes en foco y extrafocales, tanto con la óptica perfectamente alineada como descolimándola (mediante pequenos giros y descentramientos de los espejos). De esta manera, se hizo una evaluación de los efectos que estas alteraciones simuladas producirían en las imágenes focales y extra focales para así poder compararlas con las que realmente se han observado. Asimismo, se ha buscado información bibliográfica, en particular sobre los efectos de giros y descentramientos en las imágenes extrafocales, en lo que se ref iere a la falta de concentricidad de los círculos que forman la "dona" y a la distribución de intensidad luminosa en la misma. De ésta, l futuro un proceso que, haciendo uso de los detectores bidimensionales, nos permita Ilevar a cabo una alineación más rigurosa de la óptica del telescopio y evaluar con precisión Si variaciones en el posicionado del misesperamos desarrollar en emo producen efectos de descolimación.

PubMed

Camporro, Fernando Astur; Gutierrez Magaldi, Ignacio; Bulacio, Exequiel

2017-09-08

Introducción: El tabaquismo es la primera causa evitable de muerte en el mundo. El cigarrillo electrónico (CE), es un dispositivo que simula a los cigarrillos convencionales y permite inhalar nicotina y otras sustancias de forma vaporizada, sin combustión de tabaco. Su conocimiento por parte de la población general, así como su comercialización y consumo viene en constante aumento. Es utilizado en todo el mundo con el objetivo de disminuir el consumo de tabaco, lograr su abandono o poder utilizarlo en lugares públicos donde el consumo de cigarrillos convencionales está prohibido. Efectos nocivos sobre la salud: Su utilización se ha asociado a neumonía lipoidea e irritación de la vía aérea superior y toxicidad por nicotina. Presenta sustancias cancerígenas como nitrosaminas, formaldeido y metales como el niquel, cromo y plomo. Aumenta la resistencia de la vía aérea, efecto que es similar al que se produce después de la inhalación del humo del tabaco. Eficacia para dejar de fumar: No hay hasta el momento trabajos que demuestren con poder estadístico y buena metodología que este producto sea eficaz para dejar de fumar.  Conclusiones: De acuerdo a la evidencia disponible, no podemos descartar que el uso del cigarrillo electrónico no tenga riesgos para la salud. La seguridad y eficacia de los cigarrillos electrónicos como ayuda para el abandono del hábito tabáquico no han sido demostradas.

[Not Available].

PubMed

Aguilera Eguía, Raúl; Jorquera Pino, Paula Jessica; Salgado, Claudia Jaqueline; Flores, Cherie

2016-07-19

Introducción: según la Organización Mundial de la Salud, la obesidad se puede definir como una acumulación anormal o excesiva de grasa que puede ser yatrogénica para la salud.Objetivo: resumir las revisiones sistemáticas Cochrane y no Cochrane que evalúen el efecto de la suplementación de calcio para la disminución del Índice de masa corporal en personas obesas.Materiales y métodos: se realizó una búsqueda en la base de datos Medline (1980 - septiembre de 2015), Metabuscador TripDatabase y Epistemonikos (hasta septiembre de 2015), Cochrane BVS (hasta septiembre de 2015); se buscó de forma manual en revistas relacionadas con el tema de interés; se buscaron actas de congresos y se realizaron seguimientos de referencias relevantes y se contactó con expertos en el área.Resultados: la búsqueda preliminar arrojó un total de 7.163 artículos potencialmente elegibles. Según los criterios de elegibilidad incluimos dos revisiones sistemáticas de estudios clínicos aleatorizados.Conclusión: el suplemento de calcio, al parecer, no incidiría en la disminución del índice de masa corporal, DM 0,12 (-0,62, 0,86); p = 0,75, presentando "muy baja evidencia" según GRADE, esto quiere decir que "presenta una gran incertidumbre sobre la estimación del efecto".

Ecologia de las lombrices de tierra

Treesearch

Grizelle Gonzalez

2014-01-01

De los organismos de suelo, las lombrices de tierra son las mas conocidas y a menudo son consideradas las mas importantes por su influencia en el funcionamiento de ecosistemas de suelo (Hendriz y Bohlen, 2002). Tienen un efecto significativo en la estructura del suelo, el ciclo de nutrimentos y ls productividad de las cosechas. En terminos de biomasa, generalmente...

Effects of a 12-hour shift on mood states and sleepiness of Neonatal Intensive Care Unit nurses.

PubMed

Ferreira, Tadeu Sartini; Moreira, Clarice Zinato; Guo, James; Noce, Franco

2017-03-09

To assess the effect of a 12-hour shift on mood states and sleepiness at the beginning and end of the shift. Quantitative, cross-sectional and descriptive study.It was conducted with 70 neonatal intensive care unit nurses. The Brunel Mood Scale (BRUMS), Karolinska Sleepiness Scale (KSS), and a socio-demographic profile questionnaire were administered. When the KSS and BRUMS scores were compared at the beginning of the shift associations were found with previous sleep quality (p ≤ 0.01), and quality of life (p ≤ 0.05). Statistical significant effects on BRUMS scores were also associated with previous sleep quality, quality of life, liquid ingestion, healthy diet, marital status, and shift work stress. When the beginning and end of the shift were compared, different KSS scores were seen in the group of all nurses and in the night shift one. Significant vigor and fatigue scores were observed within shift groups. A good night's sleep has positive effects on the individual`s mood states both at the beginning and the end of the shift. The self-perception of a good quality of life also positively influenced KSS and BRUMS scores at the beginning and end of the shift. Proper liquid ingestion led to better KSS and BRUMS scores. Evaluar el efecto de un turno de 12 horas en estados de ánimo y somnolencia al principio y al final del turno. Estudio cuantitativo, transversal y descriptivo.Se realizó con 70 enfermeras de unidades de cuidados intensivos neonatales. Se administró la Escala de Humor Brunel (BRUMS), la Escala de Somnolencia de Karolinska (KSS) y un cuestionario de perfil sociodemográfico. Cuando se compararon las puntuaciones de KSS y BRUMS al comienzo del turno se encontraron asociaciones con calidad de sueño previa (p ≤ 0,01) y calidad de vida (p ≤ 0,05). Los efectos estadísticos significativos en las puntuaciones de BRUMS también se asociaron con la calidad previa del sueño, la calidad de vida, la ingestión de líquidos, la dieta saludable, el estado civil y el estrés laboral por turnos. Cuando se compararon el comienzo y el final del turno, se observaron diferentes puntuaciones de KSS en el grupo de todos los enfermeros y en el turno de noche. Se observaron puntuaciones significativas de vigor y fatiga dentro de los grupos de turnos. Dormir bien de noche tiene efectos positivos en los estados de ánimo del individuo tanto al principio como al final del turno. La autopercepción de una buena calidad de vida también influyó positivamente en las puntuaciones KSS y BRUMS al inicio y al final del turno. La ingesta de líquidos adecuada condujo a mejores puntuaciones KSS y BRUMS.

[Not Available].

PubMed

Fernández Castillo, Rafael; Cañadas de la Fuente, Gustavo R; Cañadas de la Fuente, Guillermo A; De la Fuente Solana, Emilia Inmaculada; Esteban de la Rosa, Rafael José; Bravo Soto, Juan

2016-07-19

Introducción: la obesidad y el sobrepeso presentan efectos adversos sobre la salud, lo que contribuye a la aparición de enfermedades metabólicas y cardiovasculares que ponen en peligro la integridad del injerto.Objetivo: investigar la influencia del IMC pretrasplante renal sobre el funcionamiento del injerto renal al año de trasplante mediante el estudio de cuatro métodos distintos de medir la filtración glomerular.Material y métodos: en este trabajo se ha seguido a 1.336 pacientes de ambos sexos trasplantados renales; se les realizaron mediciones pretrasplante y postrasplante de parámetros bioquímicos, mediciones antropométricas y función renal mediante medidas de filtrado glomerular.Resultados: a mayor índice de masa corporal pretrasplante se produce una disminución del filtrado glomerular medido por cuatro métodos distintos, así como mayor porcentaje de rechazos.Conclusiones: un IMC elevado pretrasplante contribuye a la disfunción del injerto, a una disminución del filtrado glomerular y a complicaciones del injerto en el primer año postrasplante.

Estudio multifrecuencia del medio interestelar cercano a HD 192281

NASA Astrophysics Data System (ADS)

Arnal, E. M.; Cappa, C.; Cichowolski, S.; Pineault, S.; St-Louis, N.

Una de las causas que modifica la estructura y dinámica del medio interestelar es la acción que los vientos de las estrellas de gran masa ejercen sobre el mismo. En este trabajo, mediante el uso de datos interferométricos obtenidos en la banda de radio en la transición de 21-cm del Hidrógeno neutro y de imágenes de la emisión de continuo en las bandas de 408 y 1420 MHz, de imágenes HIRES del satélite IRAS en 60 y 100 micrones, y de observaciones de continuo obtenidas con radiotelescopios de disco simple en 2695, 4850 y 8350 MHz se ha realizado un estudio multifrecuencia de los efectos que los vientos estelares de HD 192281, una estrella de tipo espectral O5 Vn((f))p, han tenido sobre el medio interestelar que rodea a la misma.

Estudio multifrecuencia del medio interestelar cercano a HD 192281

NASA Astrophysics Data System (ADS)

Arnal, E. M.; Cappa, C. E.; Cichowolski, S.; Pineault, S.; St-Louis, N.

Una de las causas que modifica la estructura y dinámica del medio interestelar es la acción que los vientos de las estrellas de gran masa ejercen sobre el mismo. En este trabajo, mediante el uso de datos interferométricos obtenidos en la banda de radio en la transición de λ˜21-cm del hidrógeno neutro y de imágenes de la emisión de continuo en las bandas de 408 y 1420 MHz, de imágenes HIRES del satélite IRAS en 60 y 100μm, y de observaciones de continuo obtenidas con radiotelescopios de disco simple en 2695, 4850 y 8350 MHz se ha realizado un estudio multifrecuencia de los efectos que los vientos estelares de HD 192281, una estrella de tipo espectral O5,Vn((f))p, han tenido sobre el medio interestelar que rodea a la misma.

Efecto del Programa de Entrenamiento “Manejo del Dolor” en la Documentación de Enfermería en el Expediente Electrónico

PubMed Central

Monsiváis, María Guadalupe Moreno; Guzmán, Ma. Guadalupe Interial; Flores, Paz Francisco Sauceda; Arreola, Leticia Vázquez

2012-01-01

Resumen En el presente trabajo se muestra la importancia de entrenar al personal de enfermería para mejorar la documentación en el expediente electrónico. Se eligió el manejo del dolor por ser un área prioritaria; una alta proporción de pacientes en período post operatorio cursa con dolor, por lo tanto, la documentación debe ser útil para la toma de decisiones clínicas. Se implementó un programa de entrenamiento denominado “Manejo del Dolor” dirigido al personal de enfermería. Se utilizó la tecnología de la información como herramienta para fortalecer el conocimiento con base en la revisión sistemática de la literatura; el personal de enfermería participante seleccionó la mejor evidencia; posteriormente se trabajó en la transferencia de este conocimiento a la práctica a través del diseño de un protocolo para el manejo del dolor. Se concluye que el conocimiento del manejo del dolor es fundamental para que enfermería documente con mayor precisión sus intervenciones. PMID:24199106

Relevamiento de HI en el Hemisferio Austral

NASA Astrophysics Data System (ADS)

Arnal, E. M.; Bajaja, E.; Morras, R.; Pöppel, W. G. L.

Un nuevo relevamiento de HI de todo el Hemisferio Austral, comprendido entre -90o <= δ <= -25o, está siendo observado con la antena I del IAR. El mismo es realizado con alta sensibilidad (r.m.s.<= 0.07 K) y alta resolución espectral (1 Km/s). Un total de ~50000 posiciones en el cielo serán observadas, espaciadas en una grilla (lxb) de (0.5o x 0.5o). El intervalo de velocidades cubierto en este relevamiento abarca el rango -450 km/s a +450 km/s en el sistema LSR. Esta base de datos será corregida por efectos de ``stray radiation''. Al presente se ha observado ~70% del total del relevamiento. El mismo es complementario de uno similar realizado en el Hemisferio Norte por Hartman y Burton (1996), con cubrimiento espacial, sensibilidad, resoluciones espaciales y en velocidad, similares a los del IAR. El objetivo final de ambos relevamientos es disponer de una base de datos uniforme en todo el cielo.

PubMed

Litewka, Sergio G

2010-11-01

Argentina ha sido un campo fértil para los intentos de reforma del sector salud, en la búsqueda por mejorar la calidad de sus servicios y, consecuentemente, la accesibilidad y la equidad del mismo. Los resultados obtenidos no han sido proporcionales a los esfuerzos desarrollados. Aunque la bioética debería, como forma de reflexión interdisciplinaria, participar en la fundamentación de nuevas políticas sanitarias y sus efectos sobre los usuarios, parece haber permanecido ajena, en general, a los graves problemas derivados de la corrupción, prefiriendo enfocarse en cuestiones vinculadas a planteos abstractos de justicia y solidaridad, atribuyendo los fracasos a la imposición de modelos económicos foráneos.

[Not Available].

PubMed

Sendrós Madroño, José M

2016-06-03

La atención nutricional en el paciente oncohematológico debe formar parte del tratamiento global del paciente. Las alteraciones debidas a la localización de la neoplasia y los efectos secundarios del tratamiento oncoespecífico muchas veces dificultan o impiden la alimentación oral. Esto puede dar lugar a una desnutrición y es de gran importancia su detección, valoración e intervención temprana. El primer paso en la intervención nutricional es el consejo dietético. Este artículo muestra qué aspectos deben tenerse en cuenta para poder elaborar un consejo dietético y la importancia de que este sea individualizado. Se describen como ejemplo cuatro situaciones especiales, donde es necesario trasladar las recomendaciones nutricionales a un plan dietético. También se incide en el uso de los probióticos en pacientes inmunocomprometidos.

La Exploracion Del Contexto Social y Sus Efectos en el Programa de Espanol en Mexico Rural. (Exploring the Social Context Affecting a Pre-School Spanish Program in Rural Mexico).

ERIC Educational Resources Information Center

Finegold, Lynda

A major stumbling block for the implementation of Mexico's Global Development Plan has been the country's large rural population of Indians. One government strategy to integrate this sector into the mainstream of society has been to teach Spanish, the official language, as a second language, while at the same time fostering ethnic pride. The…

Vigilando la Calidad del Agua de los Grandes Rios de la Nacion: El Programa NASQAN del Rio Grande (Rio Bravo del Norte)

USGS Publications Warehouse

Lurry, Dee L.; Reutter, David C.; Wells, Frank C.; Rivera, M.C.; Munoz, A.

1998-01-01

La Oficina del Estudio Geologico de los Estados Unidos (U.S. Geological Survey, 0 USGS) ha monitoreado la calidad del agua de la cuenca del Rio Grande (Rio Bravo del Norte) desde 1995 como parte de la rediseiiada Red Nacional para Contabilizar la Calidad del Agua de los Rios (National Stream Quality Accounting Network, o NASOAN) (Hooper and others, 1997). EI programa NASOAN fue diseiiado para caracterizar las concentraciones y el transporte de sedimento y constituyentes quimicos seleccionados, encontrados en los grandes rios de los Estados Unidos - incluyendo el Misisipi, el Colorado y el Columbia, ademas del Rio Grande. En estas cuatro cuencas, el USGS opera actualmente (1998) una red de 40 puntos de muestreo pertenecientes a NASOAN, con un enfasis en cuantificar el flujo en masa (la cantidad de material que pasa por la estacion, expresado en toneladas por dial para cada constituyente. Aplicacando un enfoque consistente, basado en la cuantificacion de flujos en la cuenca del Rio Grande, el programa NASOAN esta generando la informacion necesaria para identificar fuentes regionales de diversos contaminantes, incluyendo sustancias qui micas agricolas y trazas elementos en la cuenca. EI efecto de las grandes reservas en el Rio Grande se puede observar segun los flujos de constituyentes discurren a 10 largo del rio. EI analisis de los flujos de constituyentes a escala de la cuenca proveera los medios para evaluar la influencia de la actividad humana sobre las condiciones de calidad del agua del Rio Grande.

[Not Available].

PubMed

Vizuet Vega, Norma Isela; Shamah Levy, Teresa; Gaona Pineda, Elsa Berenice; Cuevas Nasu, Lucía; Méndez Gómez-Humarán, Ignacio

2016-07-19

Introducción: la anemia es un factor de riesgo en la población infantil con consecuencias graves para su crecimiento y desarrollo. Los programas de ayuda alimentaria pueden contribuir a su prevención y control. Objetivo: estudiar la adherencia al consumo de suplementos y su relación con la prevalencia de anemia en niños menores de tres años de edad en San Luis Potosí, México beneficiarios del programa PROSPERA.Métodos: se realizó un análisis comparativo en niños de 12 a 36 meses que consumen diferentes suplementos alimenticios: 414 pertenecientes al grupo de intervención y 334 al de comparación. Se midió la hemoglobina (Hb) por Hemocue clasificando como anémicos a quienes tuvieron valores <110 g/l. Se aplicaron pruebas de t de Student y X2. Se estimaron efectos de intervención mediante el método de diferencias en diferencias y un puntaje de adherencia al consumo de suplementos.Resultados: al final del estudio la prevalencia de anemia disminuyó 11.2 pp en el grupo de intervención y 8.7 pp en el de comparación; la interacción del puntaje de adherencia por suplemento y etapa de observación mostró que la adherencia al consumo de Bebida láctea + Vitaniño reduce el riesgo de presentar anemia (p = 0,14). El consumo de Nutrisano + Vitaniño se asoció con menor riesgo (0,2), ambos con respecto al consumo de Nutrisano.Conclusiones: el programa PROSPERA tuvo efectos importantes en la disminución de las prevalencias de anemia. Se recomienda llevar a cabo acciones para mejorar la adherencia al consumo de suplementos alimenticios, a fIn de mejorar la efectividad de los programas.

QUALITY, HEALTH SYSTEM AND GOVERNANCE. THE ARGENTINEAN CASE

PubMed Central

Litewka, Sergio G.

2011-01-01

Argentina ha sido un campo fértil para los intentos de reforma del sector salud, en la búsqueda por mejorar la calidad de sus servicios y, consecuentemente, la accesibilidad y la equidad del mismo. Los resultados obtenidos no han sido proporcionales a los esfuerzos desarrollados. Aunque la bioética debería, como forma de reflexión interdisciplinaria, participar en la fundamentación de nuevas políticas sanitarias y sus efectos sobre los usuarios, parece haber permanecido ajena, en general, a los graves problemas derivados de la corrupción, prefiriendo enfocarse en cuestiones vinculadas a planteos abstractos de justicia y solidaridad, atribuyendo los fracasos a la imposición de modelos económicos foráneos. PMID:21660255

Efectos del huracán Georges en la composición de especies y estructura de un bosque secundario en el interior de Puerto Rico

Treesearch

A.E. Lugo; C.M. Domínguez Cristóbal; N. Méndez Irizarry

2005-01-01

From 1995 to 2003 we studied species composition and structure in a secondary subtropical wet forest in Utuado Puerto Rico. During September 21-22, 1998, hurricane Georges passed through the stand with maximum sustained winds of 184 km/h and gusts of 240 km/h. Species richness increased after the hurricane. While native species Miconia prasina reduced its Importance...

Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.

PubMed

Chung, W Joon; Goeckeler-Fried, Jennifer L; Havasi, Viktoria; Chiang, Annette; Rowe, Steven M; Plyler, Zackery E; Hong, Jeong S; Mazur, Marina; Piazza, Gary A; Keeton, Adam B; White, E Lucile; Rasmussen, Lynn; Weissman, Allan M; Denny, R Aldrin; Brodsky, Jeffrey L; Sorscher, Eric J

2016-01-01

Small molecules that correct the folding defects and enhance surface localization of the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) comprise an important therapeutic strategy for cystic fibrosis lung disease. However, compounds that rescue the F508del mutant protein to wild type (WT) levels have not been identified. In this report, we consider obstacles to obtaining robust and therapeutically relevant levels of F508del CFTR. For example, markedly diminished steady state amounts of F508del CFTR compared to WT CFTR are present in recombinant bronchial epithelial cell lines, even when much higher levels of mutant transcript are present. In human primary airway cells, the paucity of Band B F508del is even more pronounced, although F508del and WT mRNA concentrations are comparable. Therefore, to augment levels of "repairable" F508del CFTR and identify small molecules that then correct this pool, we developed compound library screening protocols based on automated protein detection. First, cell-based imaging measurements were used to semi-quantitatively estimate distribution of F508del CFTR by high content analysis of two-dimensional images. We evaluated ~2,000 known bioactive compounds from the NIH Roadmap Molecular Libraries Small Molecule Repository in a pilot screen and identified agents that increase the F508del protein pool. Second, we analyzed ~10,000 compounds representing diverse chemical scaffolds for effects on total CFTR expression using a multi-plate fluorescence protocol and describe compounds that promote F508del maturation. Together, our findings demonstrate proof of principle that agents identified in this fashion can augment the level of endoplasmic reticulum (ER) resident "Band B" F508del CFTR suitable for pharmacologic correction. As further evidence in support of this strategy, PYR-41-a compound that inhibits the E1 ubiquitin activating enzyme-was shown to synergistically enhance F508del rescue by C18, a small molecule corrector. Our combined results indicate that increasing the levels of ER-localized CFTR available for repair provides a novel route to correct F508del CFTR.

Population size and selection intensity effects on short-term response for a selection index in Tribolium.

PubMed

Campo, J L; Turrado, H

1997-01-12

The effects of population size and selection intensity on the short-term response to selection were investigated in an experiment with Tribolium, using a two-trait empirical selection index for pupal and adult weights. Twenty lines were selected following a factorial design of five population sizes (1, 2, 4, 8, and 16 pairs of parents) and four selection intensities (20, 25, 33, and 50%), with three replicates. For each replicate, an unselected control with 16 pairs of parents was produced. There were four generations of selection per line. Selection response was significant in all lines with the 20% selection intensity and/or the 16-pair population size. Selection intensity and population size were significant effects and there was significant interaction between them. Higher selection intensities produced more overall significant response to selection (20% > (25% = 33%) > 50%); this significance was also found for the 16-pair population size. There was an overall significant difference among population sizes, with the larger population sizes giving more response than the smaller sizes (16-pair = 8-pair = 4-pair) > (2-pair = 1-pair); this significance was also found for the 20% selection intensity. There was a good agreement between observed and expected responses, except for the 50% selection intensity and/or 1-pair population size; expected values in generation 1 overestimated observed values. The realized heritability was similar in all lines. With equal and high numbers of individuals scored, it was better to choose a high selection intensity than a large population size. The results show that the effect of population size cannot be ignored, even in short-term selection response; the main influence of population size is through selection differential. RESUMEN: Los efectos del tamaño de población y la intensidad de selección sobre la respuesta a corto plazo para un índice de selección en Tribolium Los efectos del tamaño de población y la intensidad de selección sobre la respuesta a la selección a corto plazo fueron estudiados en un experimento con Tribolium usando un índice empírico de selección para dos caracteres (peso de pupa y peso adulto). Se seleccionaron 20 líneas siguiendo un modelo factorial de cinco tamaños de población (1, 2, 4, 8 y 16 pares de padres) y cuatro intensidades de selección (20, 25, 33 y 50%), con tres repeticiones. En cada repetición, había una línea control sin seleccionar con 16 pares de padres. Se hicieron cuatro generaciones de selección, por línea. La respuesta a la selección fue significativa en todas las líneas con el 20% de intensidad de selección y/o 16 pares de padres. Tanto la intensidad de selección como el tamaño de población fueron efectos significativos y hubo interacción significativa entre ellos. Las intensidades de selección más altas produjeron significativamente más respuesta en general (20% > (25% = 33%) > 50%), y esta significación se mantenía cuando el tamaño de población era de 16 pares de padres. Hubo diferencias significativas entre tamaños de población, dando los mayores tamaños más respuesta en general que los menores tamaños (16 pares = 8 pares = 4 pares) > (2 pares = 1 par), manteniendose esta significación para la intensidad de selección del 20%. La concordancia entre las respuestas observadas y las esperadas era buena, excepto cuando la intensidad de selección era 50% y/o el tamaño de población era 1 par de padres; los valores esperados en la generación 1 sobreestimaban los valores observados. La heredabilidad realizada fue similar en todas las líneas. Cuando el número total de animales era igual y alto, era mejor elegir una intensidad de selección alta que un tamaño de población grande. Los resultados indican que el efecto del tamaño de población no se puede ignorar incluso en experimentos de selección a corto plazo, y que la influencia principal de este efecto es a través del diferencial de selección. 1997 Blackwell Verlag GmbH.

Chemical Biology Probes from Advanced DNA-encoded Libraries.

PubMed

Salamon, Hazem; Klika Škopić, Mateja; Jung, Kathrin; Bugain, Olivia; Brunschweiger, Andreas

2016-02-19

The identification of bioactive compounds is a crucial step toward development of probes for chemical biology studies. Screening of DNA-encoded small molecule libraries (DELs) has emerged as a validated technology to interrogate vast chemical space. DELs consist of chimeric molecules composed of a low-molecular weight compound that is conjugated to a DNA identifier tag. They are screened as pooled libraries using selection to identify "hits." Screening of DELs has identified numerous bioactive compounds. Some of these molecules were instrumental in gaining a deeper understanding of biological systems. One of the main challenges in the field is the development of synthesis methodology for DELs.

Regulación del flujo sanguíneo uterino. I. Funciones de estrógeno y receptores estrogénicos α/β en el endotelio vascular uterino durante el embarazo

PubMed Central

Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

2015-01-01

Resumen El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsable por las adaptaciones endoteliales uterinas durante el embarazo al corto y largo plazo. Las diferencias moleculares y estructurales, junto con los diferentes efectos causados por estos receptores en las células y los tejidos, sugieren que su función varía dependiendo de la manera en la cual el estrógeno se comunica con sus receptores. En ésta revisión bibliográfica se discuten la función del estrógeno y sus receptores clásicos en las adaptaciones cardiovasculares durante el embarazo y la expresión de los Res in vivo e in vitro en el endotelio de la arteria uterina durante el ciclo ovárico y el embarazo, a la vez comparado con la expresión en endotelio arterial de tejidos reproductivos y no reproductivos. Estos temas integran el conocimiento actual de este amplio campo científico con interpretaciones e hipótesis diversas relacionadas con los efectos estrogénicos mediados bien sea por uno o los dos REs. Esta revisión también incluye la relación con las adaptaciones vasodilatadoras y angiogénicas requeridas para modular el dramático incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113750

El uso de la neuromodulación para el tratamiento del temblor

PubMed Central

Bendersky, Damián; Ajler, Pablo; Yampolsky, Claudio

2014-01-01

Introducción: El temblor puede ser un desorden incapacitante y el tratamiento de primera línea para estos pacientes es farmacológico. Sin embargo, este tratamiento puede llevar a una reducción satisfactoria del temblor en sólo el 50% de los pacientes con temblor esencial. La talamotomía era el tratamiento de elección para el temblor refractario al tratamiento médico hasta que comenzó a utilizarse la estimulación cerebral profunda (ECP) del núcleo ventral intermedio (Vim) del tálamo. En la actualidad, raramente se realiza la talamotomía. Métodos: Este artículo es una revisión no sistemática de las indicaciones, resultados, parámetros de programación y técnica quirúrgica de la ECP del Vim para el tratamiento del temblor. Resultados: Aunque los resultados clínicos son similares usando la talamotomía o la ECP del Vim, la primera causa más efectos adversos que la última. Además, la ECP puede ser usada bilateralmente, mientras que la talamotomía tiene un alto riesgo de causar disartria cuando se realiza de ambos lados. La ECP del Vim logró una adecuada mejoría del temblor en varias series de pacientes con temblor causado por temblor esencial, enfermedad de Parkinson o esclerosis múltiple. Además del Vim, hay otros blancos que están siendo usados por varios autores, tales como la zona incerta y las radiaciones prelemniscales. Conclusión: La ECP del Vim es un tratamiento útil para el temblor incapacitante refractario al tratamiento médico. Es esencial realizar una precisa selección de pacientes, así como utilizar una técnica quirúrgica correcta. Aún se desconoce el mejor blanco estereotáctico para el temblor, aunque el Vim es el más usado. PMID:25165613

Efectos Especiales de Anclaje (Estudio sobre Regresiones de Juicios Condicionales). Parte 2: Invariancia del Juicio No-Condicional Como Valor Estandar Para el Juicio Condicional (Special Effects of Anchoring (Study of Regression of Conditional Judgements) Part 2: Invariance of Unconditional Judgments as Standard Value for the Conditional Judgment). Publication No. 31.

ERIC Educational Resources Information Center

Lopez Alonso, A. O.

From the best-fit lines corresponding to sets of families of conditional judgements, the constant stimulus family and the constant condition family, both defined for a same scale object, the coordinate values of the point of intersection of both lines (indifference point) are obtained. These values are studied in relation to the mean values of the…

PubMed

Bueno Vargas, Pilar; Manzano Martín, Manuel; López-Aliaga, Inmaculada; López Pedrosa, José M ª

2016-09-20

Introducción: la gestación y lactancia están relacionadas con pérdidas temporales en la densidad mineral ósea (DMO) materna. Una suplementación con calcio podría resultar beneficiosa para evitar la pérdida de masa ósea del esqueleto materno. Otros nutrientes como los prebióticos han sido identificados como responsables de un incremento en la absorción de minerales, pudiendo condicionar la mineralización ósea.Objetivo: estudiar el efecto de la suplementación de la dieta materna con el prebiótico inulina enriquecida con oligofructosa, durante la gestación y la lactancia sobre el contenido mineral óseo (CMO) y la DMO al final del periodo de lactancia.Métodos: las ratas gestantes fueron alimentadas con dieta estándar (grupo CC), dieta fortificada en calcio (grupo Ca) o enriquecida con el prebiótico inulina enriquecida con oligofructosa (grupo Pre) hasta el final del periodo de lactancia. Posteriormente se evaluó el CMO y DMO por absorciometría de rayos X (DEXA) y el pH del contenido cecal.Resultados:en términos generales, el grupo Pre presenta los mayores valores absolutos de CMO y DMO de entre los tres grupos, siendo en la tibia significativamente diferentes en los grupos CC y Pre frente al grupo Ca. El pH del contenido cecal del grupo Pre es significativamente inferior al de los grupos CC y Ca.Conclusión:la suplementación con inulina enriquecida con oligofructosa, en condiciones nutricionales no deficientes en calcio, durante la gestación y la lactancia, ejerce una protección del esqueleto materno en las ratas y puede ser considerada como una estrategia nutricional para proteger la masa ósea materna en el periodo perinatal.

Hacia el consumo informado de tabaco en México: efecto de las advertencias con pictogramas en población fumadora

PubMed Central

Thrasher, James F; Pérez-Hernández, Rosaura; Arillo-Santillán, Edna; Barrientos-Gutiérrez, Inti

2015-01-01

Resumen Objetivo Evaluar el efecto de las advertencias sanitarias (AS) con pictogramas en las cajetillas de tabaco en adultos fumadores. Material y métodos Cohorte de fumadores con representatividad poblacional de siete ciudades mexi canas, antes (2010) y después (2011) de la implementación de AS con pictogramas (ASP). Para determinar el cambio en las variables sobre el impacto cognitivo y conductual de las advertencias, se estimaron modelos bivariados y ajustados de ecuaciones de estimación generalizada. En el Segundo levantamiento (2011), se estimaron modelos para determiner los factores que se asocian con el reporte de recordar cada advertencia que había entrado al mercado, además de los factores asociados con el autorreporte del impacto de cada advertencia vigente. Resultados Se observaron incrementos importantes de 2010 a 2011 en los conocimientos sobre los riesgos de fumar, los componentes tóxicos del tabaco y el número telefónico para recibir consejos sobre dejar de fumar. La recordación e impacto de las primeras advertencias con pictogramas parecen ser amplios y equitativos a través de la población fumadora. En comparación con 2010, un mayor nivel de ex fumadores entrevistados en 2011 reportaron que las advertencias habían influido mucho en dejar de fumar (RM=2.44, 95% IC 1.27–4.72). Conclusiones Las AS con pictogramas han logrado un impacto importante en el conocimiento y conducta, información relevante para la población y en tomadores de decisiones. PMID:22689162

[In Process Citation].

PubMed

Caravalí-Meza, Nuris Yohana; Jiménez-Cruz, Arturo; Bacardí-Gascón, Montserrat

2016-03-25

Antecedentes: se ha reportado una asociación entre el aumento del consumo de bebidas azucaradas y varias enfermedades metabólicas. Objetivo: evaluar el efecto del consumo de bebidas azucaradas sobre la obesidad en un periodo de 12 meses en mexicanos de 15 a 19 años. Métodos: el diseño del estudio fue prospectivo, con 12 meses de seguimiento. Se midieron el peso, la talla y la circunferencia de cintura (CC), y se calculó el puntaje z de índice de masa corporal (IMC). Se aplicó un cuestionario sobre consumo de 19 bebidas. Para evaluar la predicción del aumento de IMC y de CC como resultado del consumo de bebidas, se utilizó análisis de regresión logística binomial. Resultados: al final del estudio se evaluó al 89% (1.344). El promedio de edad fue de 15 años, 55% fueron mujeres. La prevalencia de sobre- peso y obesidad al final del estudio fue del 33%. Al final del estudio, un 25% de los participantes consumían más de 50 g de azúcar proveniente de las bebidas. Quienes consumieron 50 g de azúcar o más al día presentaron mayor riesgo de aumentar la CC ≥ 2 cm (RR = 1,19, IC 95%, 1,03-1,39, p = 0,02). Quienes mantuvieron el consumo de bebidas azucaradas durante 12 meses, al compararlo con los que disminuyeron el consumo a 10 g/día, presentaron 71% más probabilidades de aumentar a un puntaje de IMC ≥ 2 (RR = 1,71, IC 95%, 1,03-2,86, p = 0,039). Conclusión: el alto consumo de bebidas azucaradas aumentó las probabilidades de aumentar de peso y de circunferencia de cintura.

Reliability and construct validity of the Instrument to Measure the Impact of Valve Heart Disease on the Patient's Daily Life.

PubMed

Anjos, Daniela Brianne Martins Dos; Rodrigues, Roberta Cunha Matheus; Padilha, Kátia Melissa; Pedrosa, Rafaela Batista Dos Santos; Gallani, Maria Cecília Bueno Jayme

2016-12-19

evaluate the practicality, acceptability and the floor and ceiling effects, estimate the reliability and verify the convergent construct's validity with the instrument called the Heart Valve Disease Impact on daily life (IDCV) of the valve disease in patients with mitral and or aortic heart valve disease. data was obtained from 86 heart valve disease patients through 3 phases: a face to face interview for a socio-demographic and clinic characterization and then other two done through phone calls of the interviewed patients for application of the instrument (test and repeat test). as for the practicality and acceptability, the instrument was applied with an average time of 9,9 minutes and with 110% of responses, respectively. Ceiling and floor effects observed for all domains, especially floor effect. Reliability was tested using the test - repeating pattern to give evidence of temporal stability of the measurement. Significant negative correlations with moderate to strong magnitude were found between the score of the generic question about the impact of the disease and the scores of IDCV, which points to the validity of the instrument convergent construct. the instrument to measure the impact of valve heart disease on the patient's daily life showed evidence of reliability and validity when applied to patients with heart valve disease. avaliar a praticabilidade, aceitabilidade e os efeitos teto e chão, estimar a confiabilidade e verificar a validade de construto convergente do Instrumento para Mensuração do Impacto da Doença no Cotidiano do Valvopata em pacientes com valvopatia mitral e/ou aórtica. dados foram obtidos junto a 86 pacientes valvopatas por meio de três etapas: uma entrevista presencial para caracterização sociodemográfica e clínica e as duas outras realizadas por meio de contato telefônico para as aplicações do instrumento (Teste e teste de repetição). quanto à praticabilidade e aceitabilidade, o instrumento foi aplicado com tempo médio de 9,9 minutos e com 110% de respostas, respectivamente. Constatados efeitos teto e chão para todos os domínios, principalmente efeito chão. A confiabilidade foi testada por meio do teste-teste de repetição, obtendo-se evidências de estabilidade temporal da medida. Foram constatadas correlações negativas significantes de moderada a forte magnitude entre o escore da questão genérica sobre o impacto da doença e os escores do IDCV, o que aponta para validade de construto convergente do instrumento. o Instrumento para Mensuração do Impacto da Doença no Cotidiano do Valvopata apresentou evidências de confiabilidade e validade quando aplicado em pacientes com valvopatia. evaluar la viabilidad, aceptabilidad y los efectos techo y suelo, estimar la confiabilidad y verificar la validez de constructo convergente del Instrumento para Medir el Impacto en lo Cotidiano (IDCV) del sujeto con valvulopatías mitral y/o aórtica. los datos fueron obtenidos de 86 pacientes con valvulopatías por medio de tres etapas: una entrevista presencial para caracterización sociodemográfica y clínica y las otras dos realizadas por medio de contacto telefónico para las aplicaciones del instrumento (test y test de repetición). en cuanto a la viabilidad y aceptabilidad, el instrumento fue aplicado con un tiempo promedio de 9,9 minutos y con 110% de respuestas, respectivamente. Fueron constatados los efectos techo y suelo para todos los dominios, principalmente el efecto suelo. La confiabilidad fue comprobada por medio del test de repetición, obteniéndose evidencias de estabilidad temporal de la medida. Fueron constatadas correlaciones negativas significativas de moderada a fuerte magnitud entre el puntaje de la pregunta genérica sobre el impacto de la enfermedad y los puntajes del IDCV, lo que apunta para la validez de constructo convergente del instrumento. el instrumento para medir el impacto de la valvulopatía en lo cotidiano del sujeto, presentó evidencias de confiabilidad y validez cuando aplicado en pacientes con esa enfermedad.

Efectos de la irradiación iónica en hielos de moléculas carbonadas

NASA Astrophysics Data System (ADS)

Satorre, M. A.

En Astrofísica podemos encontrar numerosos contextos en los cuales se observan moléculas en estado sólido que, en condiciones estándar de presión y temperatura, se encontrarían como gases o líquidos. Dichas moléculas se denominan hielos y han sido observadas en nubes densas del medio interestelar, en envolturas circumestelares, en satélites del Sistema Solar, en cometas, etc. Los hielos pueden ser alterados en su composición química debido a diversos factores como por ejemplo variaciones de temperatura o aportes energéticos por parte de la irradiación, ya sea tanto de fotones ultravioleta como de iones. Dependiendo del escenario astrofísico que analicemos, unos factores cobran más importancia que otros. Los experimentos de laboratorio muestran el efecto que produce sobre la composición de los hielos la irradiación iónica, en particular sobre los que contenían alguna molécula con átomos de carbono. Dicha composición se analiza con espectroscopía IR en el rango de 2 a ˜ 25μ m. La aplicabilidad de los resultados de los experimentos es distinta dependiendo de la composición química inicial de los hielos, del tipo de ion utilizado y de la dosis total de irradiación. Existen efectos generales de la irradiación sobre la materia en los experimentos de relevancia astrofísica como son: - la formación de nuevas moléculas, que pueden incluir o no el ion incidente; - la progresiva pérdida de hidrógeno (carbonización) cuando irradiamos muestras que originalmente contienen una determinada relación carbono/hidrógeno; - la variación de la temperatura de sublimación que presentan algunos hielos. Esto puede suceder tanto en hielos que estaban presentes antes de la irradiación como en hielos formados por ésta. Se presentará el papel del ion en la formación de nuevas moléculas a partir de las que originalmente se encontraban en el hielo. Al penetrar en él, el ion provoca distintos procesos como rotura de enlaces y excitaciones electrónicas. En la mayor parte de los casos las especies producidas por la rotura del enlace, se recombinan volviendo a formar la molécula original. Sin embargo un pequeño porcentaje es capaz de formar nuevas moléculas. Si el ion queda implantado en el hielo y es reactivo (H+, C+,ldots) podría formar parte de una molécula nueva que incorpora un átomo que inicialmente no se encontraba presente en el hielo. También se presentará un contraejemplo para demostrar que no es posible asegurar que siempre que implantemos un ion reactivo, éste formará parte de nuevas moléculas en la mezcla. También se presentará la formación de nuevas moléculas a partir de la irradiación de hielos de metano, que llevan a la formación de otros compuestos como acetileno, eteno, etano,... en los cuales la relación C/H ha variado. Además de estos compuestos se forma también un residuo carbonoso (refractario) que es estable a temperatura ambiente y cuya composición química no es bien conocida. Por último, el aumento de la temperatura de sublimación es también una consecuencia de la irradiación, aunque la magnitud del aumento depende de la mezcla original y de la irradiación sufrida. Existen moléculas que llegan a variar su temperatura de sublimación en decenas de grados. Para el caso de moléculas carbonadas se forman especies por irradiación que son estables a temperatura ambiente. Con todo ello se muestra que los experimentos de laboratorio pueden ayudarnos a comprender la formación, destrucción y variación de las propiedades físicas de los hielos de interés astrofísico con la irradiación.

El nuevo panorama de la Dinámica Galáctica

NASA Astrophysics Data System (ADS)

Pivovaroff, Michael James

En general, la tendencia imperante en Dinámica Galáctica ha sido considerar que los movimientos estelares son básicamente regulares y que el caos no tiene mayor relevancia en los sistemas estelares. Sin embargo, en el último lustro se vienen acumulando pruebas de la importancia del movimiento caótico en ciertos sistemas estelares que existen en la naturaleza. Por una parte, sobre todo el grupo de David Merritt, lo ha mostrado en los casos de galaxias elípticas con concentraciones centrales de materia; por otra parte, en nuestro propio grupo, lo hemos mostrado para el caso de los satélites galácticos. Las consecuencias de estos hallazgos son tanto de tipo técnico, por la necesidad de construir modelos que contengan órbitas caóticas, como astrofísico, por los efectos del caos sobre la estacionariedad y evolución de los sistemas estelares en los que se presenta.

Refuge-effect hypothesis and the demise of the Dodo.

PubMed

Roberts, David L

2013-12-01

The Dodo was last sighted on the inshore island of Ile d'Ambre in 1662, nearly 25 years after the previous sighting on the mainland of Mauritius. It has been suggested that its survival on the inshore island is representative of the refuge effect. Understanding what constitutes significant persistence is fundamental to conservation. I tested the refuge-effect hypothesis for the persistence of the Dodo (Raphus cucullatus) on an inshore island beyond that of the mainland population. For a location to be considered a refuge, most current definitions suggest that both spatial and temporal isolation from the cause of disturbance are required. These results suggest the island was not a refuge for the Dodo because the sighting in 1662 was not temporally isolated from that of the mainland sightings. Furthermore, with only approximately 350 m separating Ile d'Ambre from the mainland of Mauritius, it is unlikely this population of Dodos was spatially isolated. Hipótesis del Efecto Refugio y la Desaparición del Dodo. © 2013 Society for Conservation Biology.

Astronomía Gamma desde El Leoncito

NASA Astrophysics Data System (ADS)

Rovero, A. C.; Colombo, E.; Sahade, J.; Weekes, T. C.

La astronomía gamma, en el extremo de energías detectadas hasta el presente, se encuentra en desarrollo en muchas partes del mundo y proporciona resultados sorprendentes a medida que la tecnología avanza en el desarrollo de nuevos detectores. La técnica Cherenkov Atmosférica es la utilizada para la detección, mediante telescopios en tierra, del efecto secundario causado por la radiación gamma de muy altas energías (E ≈ TeV). Por medio de telescopios o arreglos de detectores y utilizando la técnica mencionada, se han podido detectar algunas fuentes puntuales de mucha importancia astrofísica como la Nebulosa del Cangrejo y la galaxia de núcleo activo Markarian 421. El sistema instalado en San Juan, en cooperación con el grupo de Radiación Gamma del Observatorio Whipple, está constituído por tres colectores de 1.5m que registran pulsos de luz generados por las cascadas de partículas producidas por rayos cósmicos de todo tipo al entrar en la atmósfera terrestre. El sistema opera por barrido en ascención recta de la fuente observada que, para esta etapa del experimento, es el Centro Galáctico. Esta fuente extensa es conocida como emisor gamma de energías inferiores al TeV y ha sido observada anteriormente en este rango de energía desde el hemisferio norte pero con elevaciones bajas, situación no óptima para este tipo de técnica. Se presentan los primeros resultados del análisis de los datos obtenidos observando la región del Centro Galáctico, luego de dos años de observaciones, así como una descripción de la técnica Cherenkov Atmosférica y del equipo utilizado en la experiencia.

Distinción Empírica Entre Engagement y Trabajolismo en Enfermeras Hospitalarias de Japón: Efecto Sobre la Calidad del Sueño y el Desempeño Laboral

PubMed Central

Kubota, Kazumi; Shimazu, Akihito; Kawakami, Norito; Takahashi, Masaya; Nakata, Akinori; Schaufeli, Wilmar B.

2016-01-01

Objetivo El objetivo de este estudio es demostrar la distinción entre engagement y trabajolismo, estudiando su relación con la calidad del sueño y el desempeño laboral. Método Un total de 447 enfermeras de 3 hospitales de Japón fueron entrevistadas mediante un cuestionario autoadministrado que incluía la escala Utrecht (UWES, Utrecht Work Engagement Scale), la Escala de Adicción al Trabajo Holandesa (DUWAS, Dutch Workaholism Scale), preguntas sobre la calidad del sueño (7 ítems) con respecto a (1) dificultad para conciliar el sueño, (2) dificultad para mantener el sueño, (3) despertar temprano por la mañana, (4) dormirse o tomar siestas durante el día, (5) somnolencia diurna excesiva en el trabajo, (6) dificultad para despertarse por la mañana, y (7) despertar cansado en la mañana, y el Cuestionario sobre Salud y Desempeño (CSD) de la Organización Mundial de la Salud. Resultados Los modelos de ecuaciones estructurales demostraron que el engagement se relaciona positivamente con la calidad del sueño y el rendimiento laboral, mientras que el trabajolismo tiene una relación negativa con la calidad del sueño y el desempeño laboral. Conclusión Los resultados indican que el engagement y el trabajolismo son conceptualmente diferentes. El primero tiene una connotación positiva, mientras que el segundo se asocia de manera negativa al bienestar (buena calidad del sueño y buen rendimiento en el trabajo). PMID:26752805

Effects of the application of therapeutic massage in children with cancer: a systematic review.

PubMed

Rodríguez-Mansilla, Juan; González-Sánchez, Blanca; Torres-Piles, Silvia; Martín, Jorge Guerrero; Jiménez-Palomares, María; Bellino, Macarena Núñez

2017-06-08

to learn about the effects of the use of therapeutic massage in children with cancer. systematic review of controlled clinical trials The search was conducted in November 2014 in the following databases: Pubmed, CSIC, Dialnet, Scopus, Cochrane and PEDro. Inclusion criteria were: clinical trials, published in English or Spanish, analyzing the effects of massage on the different stages and types of childhood cancer (between 1 and 18 years old). of 1007 articles found, 7 met the inclusion criteria. Their authors use different massage techniques (Swedish massage, effleurage, petrissage, frictions, pressures), obtaining benefits in the symptoms present during the illness (decrease of pain, nausea, stress, anxiety and increase of white blood cells and neutrophils). therapeutic massage improves the symptoms of children with cancer, but there is a need for more research that may support the effects attributed to it. conocer los efectos del uso del masaje terapéutico en niños con cáncer. revisión sistemática de ensayos clínicos controlados la búsqueda se llevó a cabo en noviembre de 2014 en las bases de datos científicas: Pubmed, CSIC, Dialnet, Scopus, Cochrane y PEDro. Los criterios de inclusión han sido: ensayos clínicos, publicados en inglés o español, en los que se analizaran los efectos del masaje en las diferentes etapas y tipos de cáncer infantil (entre 1 y 18 años). de 1007 artículos localizados, 7 cumplieron los criterios de inclusión. Sus autores utilizan diferentes técnicas de masaje (masaje sueco, effleurage, petrissage, fricciones, presiones), obteniendo beneficios en los síntomas presentes durante la enfermedad (disminución del dolor, náuseas, estrés, ansiedad y aumento de glóbulos blancos y neutrófilos). el masaje terapéutico mejora los síntomas de los niños con cáncer, que respalden los efectos que se le atribuyen. conhecer os efeitos do uso da massagem terapêutica em crianças com câncer. revisão sistemática de ensaios clínicos controlados. A pesquisa foi realizada em novembro de 2014 em bases de dados científicas: Pubmed, CSIC, Dialnet, Scopus, Cochrane and PEDro. Os critérios de inclusão foram: ensaios clínicos, publicados em inglês ou espanhol, analisando os efeitos da massagem nas diferentes fases e tipos de câncer infantil (entre 1 e 18 anos). de 1007 artigos encontrados, 7 preencheram os critérios de inclusão. Os autores utilizam diferentes técnicas de massagem (massagem sueca, effleurage, petrissage, fricções, pressões), obtendo benefícios nos sintomas presentes durante a doença (diminuição da dor, náusea, estresse, ansiedade e aumento de glóbulos brancos e neutrófilos). a massagem terapêutica melhora os sintomas das crianças com câncer, mas são necessárias mais pesquisas que apoiem os efeitos atribuídos a ela.

Accounting for the Impact of Conservation on Human Well-Being

PubMed Central

Milner-Gulland, EJ; Mcgregor, JA; Agarwala, M; Atkinson, G; Bevan, P; Clements, T; Daw, T; Homewood, K; Kumpel, N; Lewis, J; Mourato, S; Palmer Fry, B; Redshaw, M; Rowcliffe, JM; Suon, S; Wallace, G; Washington, H; Wilkie, D

2014-01-01

Conservationists are increasingly engaging with the concept of human well-being to improve the design and evaluation of their interventions. Since the convening of the influential Sarkozy Commission in 2009, development researchers have been refining conceptualizations and frameworks to understand and measure human well-being and are starting to converge on a common understanding of how best to do this. In conservation, the term human well-being is in widespread use, but there is a need for guidance on operationalizing it to measure the impacts of conservation interventions on people. We present a framework for understanding human well-being, which could be particularly useful in conservation. The framework includes 3 conditions; meeting needs, pursuing goals, and experiencing a satisfactory quality of life. We outline some of the complexities involved in evaluating the well-being effects of conservation interventions, with the understanding that well-being varies between people and over time and with the priorities of the evaluator. Key challenges for research into the well-being impacts of conservation interventions include the need to build up a collection of case studies so as to draw out generalizable lessons; harness the potential of modern technology to support well-being research; and contextualize evaluations of conservation impacts on well-being spatially and temporally within the wider landscape of social change. Pathways through the smog of confusion around the term well-being exist, and existing frameworks such as the Well-being in Developing Countries approach can help conservationists negotiate the challenges of operationalizing the concept. Conservationists have the opportunity to benefit from the recent flurry of research in the development field so as to carry out more nuanced and locally relevant evaluations of the effects of their interventions on human well-being. Consideración del Impacto de la Conservación sobre el Bienestar Humano Resumen Los conservacionistas cada vez más se comprometen con el concepto del bienestar humano para mejorar el diseño y la evaluación de sus intervenciones. Desde la convención de la influyente Comisión Sarkozy en 2009, los investigadores del desarrollo han estado refinando las conceptualizaciones y los marcos de trabajo para entender y medir el bienestar humano y están comenzando a convergir con un entendimiento común de cuál es la mejor forma de hacer esto. En la conservación el término bienestar humano tiene un uso amplio, pero existe la necesidad de la orientación en su operación para medir los impactos de las intervenciones de la conservación sobre la gente. Presentamos un marco de trabajo para entender el bienestar humano que podría ser útil particularmente en la conservación. El marco de trabajo incluye tres condiciones: cumplir con las necesidades, perseguir objetivos y experimentar una calidad satisfactoria de vida. Resumimos algunas de las complejidades involucradas en la evaluación de los efectos del bienestar de las intervenciones de la conservación con el entendimiento de que el bienestar varía entre la gente, en el tiempo y con las prioridades del evaluador. Los retos clave para la investigación de los impactos del bienestar de las intervenciones de la conservación incluyen la necesidad de crear una colección de estudios de caso para trazar lecciones generalizables: hacer uso del potencial de la tecnología moderna para apoyar la investigación del bienestar; y contextualizar espacial y temporalmente las evaluaciones de los impactos de la conservación sobre el bienestar dentro del marco más amplio del cambio social. Existen caminos que atraviesan la confusión que rodea al término bienestar, y los marcos de trabajo existentes, como el del acercamiento de Bienestar en Países en Desarrollo, pueden ayudar a los conservacionistas a negociar los obstáculos de la operación del concepto. Los conservacionistas tienen la oportunidad de beneficiarse del frenesí reciente de investigación en el campo del desarrollo para así realizar evaluaciones más matizadas y relevantes localmente de los efectos de sus intervenciones sobre el bienestar humano. PMID:24641551

El efecto de la panfotocoagulación con láser en edema macular diabético con el fotocoagulador Pascal® versus el láser de argón convencional.

PubMed

Mahgoub, Mohamed M; Macky, Tamer A

2017-07-11

Objetivo: El objetivo de este estudio fue comparar el efecto de la panfotocoagulación (PFC) en el edema macular diabético (EMD) en pacientes con retinopatía diabética proliferativa (RDP) con el fotocoagulador Pascal® (FP) vs. un fotocoagulador con láser de argón convencional (FLAC). Métodos: Se aleatorizó el uso de FP o FLAC en ochenta ojos con RDP y EMD con afectación central de la mácula. Ambos grupos tuvieron una evaluación de base de mejor agudeza visual corregida y fueron examinados con tomografía de coherencia óptica y angiografía con fluoresceína. Resultados: El número medio de disparos de láser en los grupos de FP y FLAC fue 1.726,10 y 752,00 en la sesión 1 y 1.589,00 y 830,00 (p < 0,001) en la sesión 2, respectivamente. El grosor foveal central (GFC) medio antes de comenzar el estudio fue 306 ± 100 y 314 ± 98 en los grupos de FP y FLAC, respectivamente. A las 8 semanas, el GFC medio fue 332 ± 116 y 347 ± 111 en los grupos de FP y FLAC, respectivamente (p > 0,05). La MAVC media fue similar durante el periodo de estudio y no hubo ninguna diferencia significativa entre los grupos (p > 0,05). Conclusiones: El FP y el FLAC mostraron efectos similares en el EMD en ojos con RDP y fueron igualmente seguros sin un aumento significativo del GFC. © 2017 S. Karger AG, Basel.

A new approach to the study of therapeutic work in the transference.

PubMed

Pessier, J; Stuart, J

2000-02-01

This article proposes a new method for evaluating the effects of therapist and patient work in the transference. Work in the transference is often difficult for the patient, and may show a characteristic pattern of lag between a transference interpretation and its therapeutic effect. To account for this lag, we assessed patient responses to interpretations over the course of entire sessions. The narratives patients told about others, or Relationship Episodes (REs), were used as units of study. In a sample of three consecutive sessions taken from each of three psychodynamic cases, we identified several instances when transference work appeared to have an initial inhibitory effect, but facilitated progress over the course of the entire session. We recommend that to examine the effects of interpretations future studies use longer, more clinically meaningful segments of patient speech than have been used in the past. Dieser Beitrag propagiert eine neue Methode zur Evaluierung der Effekte von Übertragungsarbeit durch Therapeut und Patient. Arbeit in der Übertragung ist für den Patienten oftmals schwierig und zeigt häufig eine charakteristisches Muster von zeitlichen Verzögerungen bzgl. Übertragungsdeutungen und deren therapeutischen Effekten. Um diese zeitliche Verzögerung zu erklären, untersuchten wir die Reaktionen von Patienten auf derartige Deutungen im Verlauf ganzer Sitzungen. Narrative, in denen die Patienten über andere berichteten, also Beziehungsepisoden, dienten in dieser Studie als Einheit. In einter Stichprobe dreier aufeinanderfolgender Sitzugnen, die sich auf drei Fälle bezogen, identifizierten wir verschiedene Umstände, unter denen Übertragungsarbeit anfänglich einen hemmenden Affekt zu haben schien, letztlich aber den Gesamtverlauf der Sitzung günstig beeinflussten. Wir empfehlen, in Zukunft die Effekte von Übertragungsdeutungen auf der Basis längerer, klinische sinnvoller Segmente von Patientenäußerungen zu untersuchen als dies in der Vergangenheit der Fall war. Cet article propose une nouvelle méthode pour évaluer les effets du travail sur le transfert entre thérapeute et patient. Ce travail est souvent difficile pour le patient, et il peut y avoir un pattern caractéristique de délai entre une înterprétation de transfert et son effet thérapeutique. Pour expliquer ce délai, nous avons évalué les réponses des patients à des interprétatios au cours de séances entières. C'est les narrations des patients sur d'autres, ou Episodes Relationnels (ERs), qui ont constitué les unités de base de cette étude. Dans un échantillon de 3 séances consécutives venant de 3 cas psychodynamiques, nous avons identifié plusieurs moments où le traail sur le transfert semblait avoir un effet inhibitoire initial, mais favorisait le progrès en regardant la séance entière. Nous recommandons pour de futures études sur l'effet des interprétations de prendre des segments plus longs et cliniquement significatifs du récit du patient que ceux utilisés dans le passé. Este artículo propone un nuevo método para evaluar los efectos del trabajo de terapeuta y paciente en la transferencia. El trabajo en la transferencia es, con frecuencia, dificil para el paciente y puede mostrar un lapso característico entre una interpretación transferencial y sus efectos terapéuticos. Para explicar este lapso, hemos evaluado las respuestas del paciente a las interpretaciones a lo largo de sesiones enteras. Como unidad de estudio se usaron las narrativas de los pacientes acerca de otros, o sea, los episodios relacionales (REs). En una muestra de tres sesiones consecutivas tomadas de tres casos psicodinámicos, identificamos varioss casos en los que la trasferencia parecía tener un efecto inicial inhibitorio, aunque se vio que a lo largo de la sesión facilitaba el progreso. Recomendamos que, para examinar los efectos de las interpretaciones, los futuros estudios usen segmentos más largos y clínicamente más significativos del habia del paciente que los que se usaron en el pasado.

Generacion de Nuevas Capacidades en el Ejercito de Guatemala para el Combate al Trafico de Drogas y Delitos Conexos (Generating New Capacities within the Guatemalan Army in Order to Combat Drug Trafficking and Related Crimes)

DTIC Science & Technology

2014-06-13

la pérdida de control territorial por parte del Estado en el tema de seguridad y la poca credibilidad que la sociedad tiene en sus fuerzas...de seguridad civil y segundo: como efecto no buscado de la presión ejercida por el gobierno de Colombia y el de México en alianza con los Estados...naturales y líneas rectas que unen detalles topográficos fijados y descritos en el mismo Laudo. Para la defensa de la seguridad nacional, el Ejército

Efecto de la difusión y la velocidad en la ionización del átomo de Carbono

NASA Astrophysics Data System (ADS)

Rovira, M. G.; Fontenla, J. M.

The equations of statistical equilibrium for all ionization states of the atom are solved. The effects of diffusion and center of mass velocity are included. In order to estimate the modifications of the ionization curves, they were applied to the Carbon atom. To solve these equations, solar prominences' models obtained in a previous paper were adopted. They were extended to reach a temperature of 1.5 × 106 K and the complete model of the prominence was calculated. Ionization curves for different values of velocity, diffusion and medium models were obtained. The different models represent structures with different densities. Considerable modifications due to these effects are found.

Efecto del gas nebular sobre la dinámica de un protoplaneta Joviano

NASA Astrophysics Data System (ADS)

Cionco, R. G.; Brunini, A.

In order to describe a realist scenario to investigate the formation of giant planets, we analyze the physical structure of the primordial gaseous circumsolar disk, the environment where protoplanets growth. We calculate the gas drag efect onto embrios of 1 M⊕ at 5.2 AU with a new formulation of the dinamycal friction effect. We have found a strong radial migration of the protoplanet, that, in comparison whith the predictions of other formulations of gas drag is, at least, one order of magnitude larger. This result casts doubts about the possible survival of these kinds of planetary embrios. The implications for the modelling of the planetary systems are discussed.

Estudio fenomenologico del conocimiento curricular y conocimiento de contenido en maestros de matematica a nivel secundario

NASA Astrophysics Data System (ADS)

Cardona Tomassini, Ivan Javier

En esta investigacion se estudio el fenomeno del conocimiento de contenido y el conocimiento curricular de maestros de matermaticas y como estos dos componentes se reflejan en su conocimiento pedagogico del contenido. El conocimiento de contenido es el conocimiento que tienen los maestros de los contenidos de una disciplina y sobre la estructura de su organizacion (Shulman, 1986). El conocimiento curricular es el conocimiento que los maestros poseen sobre los componentes de un curriculo disenado para ensenar un topico de una materia especifica a un nivel particular, la variedad de instrumentos instruccionales disponibles para implementar el mismo y como utilizar los instrumentos curriculares disponibles (Ball & Bass, 2003; Choppin, 2009; Hill, Rowan, & Ball, 2005). Este estudio se enmarca en el paradigma cualitativo, teniendo como diseno el estudio fenomenologico (Lucca y Berrios, 2009; McMillan, 2004). Los participantes fueron seis maestros de matermaticas del nivel superior (10mo a 12mo grado). Al momento de la investigacion los participantes ensenaban en escuelas publicas o privadas de Puerto Rico. Para recolectar la informacion se utilizo un grupo focal en donde los maestros resolvieron seis ejercicios matematicos y posteriormente reflexionaron en forma grupal sobre las soluciones. Tambien se realizo un analisis de documentos de planificacion y se llevaron a cabo entrevistas semiestructuradas. Se exploraron los contenidos relacionados a la ecuacion de una recta, rectas verticales y horizontales, suma y multiplicacion de polinomios, resolucion de ecuaciones cuadraticas y distancia entre dos puntos del plano cartesiano. Los resultados muestran que los participantes tienen dominio procesal de los contenidos correspondientes a las rectas verticales y horizontales, la suma y multiplicacion de polinomios, el calculo distancia entre dos puntos del plano cartesiano. Sin embargo, se noto cierta dificultad en la explicacion conceptual de los contenidos relacionados a la ecuacion de la recta, las rectas verticales y horizontales y la solucion de ecuaciones cuadraticas. Lo cual permite concluir que los participantes demuestran mejor dominio del conocimiento procesal que del conocimiento conceptual. Estos es un reflejo del efecto de una instruccion enfocada en desarrollar los procesos algoritmicos ya que la explicacion con sentido de los procesos pasa a un segundo plano.

Morfología de la Coma del Cometa Hale - Bopp

NASA Astrophysics Data System (ADS)

Gil-Hutton, R.; Caballero, M.; Coldwell, G.; Cañada, M.; Godoy, G.; Trozzo, C.; Gómez, G.

Para lograr comprender plenamente los procesos físicos que se desarrollan en los núcleos cometarios y obtener un modelo que explique, no sólo su actividad, sino también sus efectos sobre la coma, es necesario obtener información detallada para el mayor número de cometas posible, siendo las características más interesantes para estudiar la ubicación de las regiones activas, la presencia de jets, las tasas de producción de gas y polvo y la interacción de la coma con el viento solar. En la actualidad, con técnicas de procesamiento de imágenes y tecnología CCD se pueden obtener este tipo de datos para cometas que ingresan al sistema solar interior y estudiar, de esta manera, la morfología de sus comas, tratando de correlacionar la actividad detectada con algún modelo teórico. En este trabajo se presenta un estudio parcial de la actividad desarrollada por el cometa Hale-Bopp, y sus efectos sobre la morfología de su coma, desde agosto de 1995 hasta la fecha en base a imágenes adquiridas con el telescopio de 0.76 m. de la Estación Astronómica Dr. Carlos Ulrrico Cesco.

Evolución Dinámica de Cúmulos Estelares Abiertos

NASA Astrophysics Data System (ADS)

de La Fuente Marcos, R.

Las estrellas que observamos no se formaron aisladamente, sino que lo hicieron en grupos o cúmulos. Estos sistemas estelares recibenel nombre de cúmulos estelares abiertos o galácticos cuando están constituidos por estrellas de la Población I. Los cúmulos abiertos se localizan preferentemente en el plano galáctico, y en muchos de ellos está teniendo lugar aún una activa formación estelar. El propósito principal de esta tesis doctoral es el estudio de la evolución dinámica de estos sistemas estelares por medio de simulaciones numéricas y de la comparación de sus resultados con datos observacionales. Con este fin se analizan los efectos que, sobre la dinámica de los cúmulos, ejercen varios fenómenos de interés astrofísico tales como el campo gravitatorio galáctico, la pérdida de masa causada por la evolución estelar y la presencia de binarias primordiales. En este trabajo se presentan los resultados de más de un centenar de modelos de cúmulos, con poblaciones comprendidas en el intervalo [100, 10.000] estrellas, calculados con NBODY5, un programa estándar en el campo de la Dinámica Estelar Experimental. De los mismos se deduce que el mecanismo principal que rige la dinámica de los cúmulos abiertos es la evolución estelar de su distribución de masas, encontrándose un comportamiento diferencial fuertemente dependiente de la población inicial del cúmulo. Los mecanismos responsables de la desintegración de los cúmulos abiertos son analizados en detalle, proponiéndose un modelo analítico que ajusta razonablemente los resultados de las simulaciones. Además, y con el fin de explicar el elevado número de sistemas múltiples observados en cúmulos abiertos, se estudian los efectos que, sobre los mismos, ejerce la presencia de una cierta fracción de binarias primordiales. El papel de las binarias tambiín depende de la riqueza del cúmulo y sus efectos se interrelacionan con aquellos debidos a la evolución estelar. Por último, se aborda la posibilidad de construir diagramas de Hertzsprung-Russell teóricos a partir de las simulaciones y compararlos con datos procedentes de cúmulos abiertos reales.

The novel c.247_249delTTC (p.F83del) GJB2 mutation in a family with prelingual sensorineural deafness.

PubMed

Petersen, Michael B; Grigoriadou, Maria; Koutroumpe, Maria; Kokotas, Haris

2012-07-01

Non-syndromic hearing loss is one of the most common hereditary determined diseases in human, and the disease is a genetically heterogeneous disorder. Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of non-syndromic recessive hearing impairment in many countries and are largely dependent on ethnic groups. Due to the high frequency of the c.35delG GJB2 mutation in the Greek population, we have previously suggested that Greek patients with sensorineural, non-syndromic deafness should be tested for the c.35delG mutation and the coding region of the GJB2 gene should be sequenced in c.35delG heterozygotes. Here we present on the clinical and molecular genetic evaluation of a family suffering from prelingual, sensorineural, non-syndromic deafness. A novel c.247_249delTTC (p.F83del) GJB2 mutation was detected in compound heterozygosity with the c.35delG GJB2 mutation in the proband and was later confirmed in the father, while the mother was homozygous for the c.35delG GJB2 mutation. We conclude that compound heterozygosity of the novel c.247_249delTTC (p.F83del) and the c.35delG mutations in the GJB2 gene was the cause of deafness in the proband and his father. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Modelo analítico del efecto de PRS sobre satélites GPS

NASA Astrophysics Data System (ADS)

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

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

Modality effect in false recognition: evidence from Chinese characters.

PubMed

Mao, Wei Bin; Yang, Zhi Liang; Wang, Lin Song

2010-02-01

Using the Deese/Roediger-McDermott (DRM) false memory method, Smith and Hunt ( 1998 ) first reported the modality effect on false memory and showed that false recall from DRM lists was lower following visual study than following auditory study, which led to numerous studies on the mechanism of modality effect on false memory and provided many competing explanations. In the present experiment, the authors tested the modality effect in false recognition by using a blocked presentation condition and a random presentation condition. The present experiment found a modality effect different from the results of the previous research; namely, false recognition was shown to be greater following visual study than following auditory study, especially in the blocked presentation condition rather than in the random presentation condition. The authors argued that this reversed modality effect may be due to different encoding and processing characteristics between Chinese characters and English words. Compared with English words, visual graphemes of critical lures in Chinese lists are likely to be activated and encoded in participants' minds, thus it is more difficult for participants to discriminate later inner graphemes from those items presented in visual modality. Hence visual presentation could lead to more false recognition than auditory presentation in Chinese lists. The results in the present experiment demonstrated that semantic activation occurring during the encoding and retrieve phases played an important role in modality effect in false recognition, and our findings might be explained by the activation-monitoring account. Utilisant la méthode de fausse mémoire de Deese/Roediger-McDermott (DRM), Smith et Hunt ( 1998 ) ont d'abord rendu compte de l'effet de modalité sur la fausse mémoire et ils ont montré que le faux rappel à partir des listes de DRM était plus faible suivant une étude visuelle plutôt qu'une étude auditive. Ceci a mené à plusieurs études sur le mécanisme de l'effet de modalité sur la fausse mémoire, lesquelles ont fourni plusieurs explications concurrentes. Dans la présente expérience, les auteurs ont testé l'effet de modalité dans la fausse reconnaissance en utilisant une condition de présentation fixe et une condition de présentation aléatoire. Cette expérience a révélé un effet de modalité différent des résultats obtenus dans les recherches antérieures. En effet, la fausse reconnaissance était plus élevée suivant une étude visuelle plutôt qu'une étude auditive, spécialement dans la condition de présentation fixe. Les auteurs suggèrent que cet effet de modalité inverse peut être dû à des caractéristiques d'encodage et de processus différentes entre les caractères chinois et les mots anglais. Comparativement aux mots anglais, les graphèmes visuels des leurres critiques dans les listes chinoises sont susceptibles d'être activés et encodés dans l'esprit des participants, rendant plus difficile de discriminer les graphèmes intériorisés plus tard de ces items présentés dans la modalité visuelle. Ainsi, la présentation visuelle pourrait mener à davantage de fausse reconnaissance que la présentation auditive dans les listes chinoises. Les résultats de la présente expérience ont démontré que l'activation sémantique se produisait durant l'encodage et que la phase de retrait jouait un rôle important dans l'effet de modalité dans la fausse reconnaissance. Nos résultats peuvent être expliqués par la théorie activation-contrôle. Utilizando el método de Deese/Roediger-McDermott (DRM) de falsa mamoria, Smith y Hunt ( 1998 ) fueron los primeros en encontrar el efecto de modalidad en la falsa memoria y demostraron que los falsos recuerdos del listado DRM fueron más bajos después de un estudio visual que después de un estudio auditivo lo cual llevó a varios estudios sobre el mecanismo del efecto de la modalidad sobre falsos recuerdos y proporcionó varias explicaciones que compiten entre sí. En el presente trabajo, los autores estudiaron el efecto de la modalidad en el falso reconocimiento utilizando una condición de presentación en bloques y otra condición de presentación de forma aleatoria. El presente experimento encontró un efecto de la modalidad diferente de los resultados de los estudios anteriores. En concreto, el reconocimiento falso ha resultado ser mayor después del estudio visual que después del estudio auditivo, especialmente en caso de la presentación en bloques en comparación con la condición de presentación aleatoria. Los autores argumentan que este efecto inverso de la modalidad puede ser causado por diferentes características de codificación y procesamiento entre caracteres chinos y palabras inglesas. En comparación con las palabras inglesas, los grafemas visuales de las palabras críticas en chino tienen probabilidad de ser activadas y codificadas en las mentes de los participantes, por tanto, es más difícil discriminar posteriores grafemas internos de los que fueron presentados en la modalidad visual. Por tanto, la presentación visual podría conducir a más falsos reconocimientos que la presentación auditiva en los listados de palabras chinas. Los resultados del presente experimento demostraron que la activación semántica durante las fases de codificación y recuperación jugó un rol importante en el efecto de falso reconocimiento según modalidad y que nuestros resultados se pueden explicar teniendo en cuenta la activación y la vigilancia.

Satisfaction with medication in coronary disease treatment: psychometrics of the Treatment Satisfaction Questionnaire for Medication.

PubMed

Liberato, Ana Carolina Sauer; Rodrigues, Roberta Cunha Matheus; São-João, Thaís Moreira; Alexandre, Neusa Maria Costa; Gallani, Maria Cecília Bueno Jayme

2016-06-07

to psychometrically test the Brazilian version of the Treatment Satisfaction Questionnaire for Medication - TSQM (version 1.4), regarding ceiling and floor effect, practicability, acceptability, reliability and validity. participants with coronary heart disease (n=190) were recruited from an outpatient cardiology clinic at a university hospital in Southeastern Brazil and interviewed to evaluate their satisfaction with medication using the TSQM (version 1.4) and adherence using the Morisky Self-Reported Measure of Medication Adherence Scale and proportion of adherence. The Ceiling and Floor effect were analyzed considering the 15% worst and best possible TSQM scores; Practicability was assessed by time spent during TSQM interviews; Acceptability by proportion of unanswered items and participants who answered all items; Reliability through the Cronbach's alpha coefficient and Validity through the convergent construct validity between the TSQM and the adherence measures. TSQM was easily applied. Ceiling effect was found in the side effects domain and floor effect in the side effects and global satisfaction domains. Evidence of reliability was close to satisfied in all domains. The convergent construct validity was partially supported. the Brazilian TSQM presents evidence of acceptability and practicability, although its validity was weakly supported and adequate internal consistency was observed for one domain. realizar o teste psicométrico da versão brasileira do Treatment Satisfaction Questionnaire for Medication - TSQM (versão 1.4) [Questionário Satisfação com Tratamento Medicamentoso] com relação aos efeitos de teto e chão, praticidade, aceitabilidade, confiabilidade e validade. os participantes com doença cardíaca coronária (n=190) foram recrutados num ambulatório de cardiologia de um hospital universitário no sudeste do Brasil e entrevistados para avaliar satisfação em relação ao tratamento medicamentoso através da TSQM (versão 1.4) e adesão através da Morisky Self-Reported Measure of Medication Adherence Scale [Medida de Auto-Relato de Adesão ao Tratamento Medicamentoso] e proporção de aderência. Os efeitos Teto e Chão foram analisados considerando os 15% piores e 15% melhores escores possíveis obtidos no TSQM; Praticidade foi avaliada pelo tempo gasto na aplicação do TSQM durante a entrevista; Aceitabilidade foi verificada pela proporção de itens não respondidos e participantes que responderam todos os itens; Confiabilidade foi verificada com o coeficiente alfa de Cronbach e Validade através da validade de construto convergente entre o TSQM e as medidas de adesão. o TSQM foi facilmente aplicado. O efeito teto foi encontrado no domínio efeitos colaterais e o efeito chão foi encontrado nos domínios efeitos colaterais e satisfação global. Evidência de confiabilidade foi próxima de satisfatória em todos os domínios. A validade de construto convergente foi parcialmente apoiada. a versão brasileira do TSQM apresenta evidência de aceitabilidade e praticidade embora sua validade tenha sido pouco apoiada e consistência interna adequada foi observada em um domínio. testar las propiedades psicométricas de la versión brasileña del Treatment Satisfaction Questionnaire for Medication - TSQM (versión 1.4), considerando los efectos techo y suelo, factibilidad, aceptabilidad, confiabilidad y validez. participantes con enfermedad coronaria (n=190) fueron reclutados de una clínica ambulatoria de cardiología en un hospital universitario en el sudeste de Brasil y entrevistados para evaluar su satisfacción con la medicación con el TSQM (versión 1.4) y su adhesión con la Morisky Self-Reported Measure of Medication Adherence Scale y proporción de adhesión. Los efectos techo y suelo fueron analizados considerando los 15% peores y mejores puntuaciones en el TSQM; la factibilidad fue evaluada por el tiempo gasto durante las entrevistas de TSQM; la aceptabilidad por la proporción de ítems no respondidos y participantes que contestaron a todos los ítems; la confiabilidad con el coeficiente alfa de Cronbach y la validez de constructo convergente entre el TSQM y las medidas de adhesión. el TSQM fue aplicado con facilidad. El efecto de techo fue encontrado en el dominio de los efectos secundarios y el efecto suelo en los dominios de efectos secundarios y satisfacción global. Las evidencias de confiabilidad fueron aproximadamente satisfechas en todos los dominios. La validez de constructo convergente fue parcialmente apoyada. la versión brasileña del TSQM presenta evidencias de aceptabilidad y factibilidad, a pesar del soporte débil a su validez y de la observación de consistencia interna adecuada para un dominio.

Salud mental en desastres naturales: estrategias interventivas con adultos mayores en sectores rurales de Chile.

PubMed

Osorio-Parraguez, Paulina; Espinoza, Adriana

2016-06-01

En el presente artículo se da a conocer una estrategia de intervención llevada a cabo con adultos mayores en la comuna de Paredones, sexta región de Chile, con posterioridad al terremoto y tsunami del 27 de febrero 2010 en Chile, en el contexto de una investigación sobre fortalezas y vulnerabilidades desplegadas por este grupo etario, con posterioridad a un desastre natural. Se presenta una descripción del desarrollo metodológico de la intervención y de los sustentos teóricos y conceptuales en los que se basa. Como resultado de este proceso, se propone una estrategia que trabaje a través de la identificación de las propias experiencias y fortalezas de los sujetos. De tal forma se minimizan los efectos negativos de los determinantes sociales de la salud (como la edad y el lugar de residencia) en contexto de crisis; permitiendo a los adultos mayores fortalecer sus recursos individuales y colectivos, en pro de su bienestar psicosocial. © The Author(s) 2015.

Expresiones de afecto de madres bilingües, Bilingual mothers' expressions of affect

PubMed Central

Shiro, Martha

2015-01-01

En la interacción de 10 madres bilingües con sus hijos de 30 meses se analiza la expresión de afectividad en L1 y en L2. Se identificaron las expresiones de emoción, volición y actitud epistémica en 30 interacciones espontáneas: i. 10 madres (español L1) hablando en L1; ii. 10 madres (español L1) hablando en inglés L2; y iii. 10 madres (inglés L1) hablando en L1. Los resultados sugieren que los usos de L2 difieren de los de L1 (inglés o español): la expresión de volición y actitud epistémica se asemeja al inglés L1, mientras que la expresión de las emociones se acerca al español L1. Estos hallazgos permiten explicar los usos del lenguaje expresivo de los bilingües y ayudan a determinar sus efectos en el desarrollo del lenguaje PMID:25844004

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

PubMed

Donaldson, Scott H; Pilewski, Joseph M; Griese, Matthias; Cooke, Jon; Viswanathan, Lakshmi; Tullis, Elizabeth; Davies, Jane C; Lekstrom-Himes, Julie A; Wang, Linda T

2018-01-15

Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D. This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day). Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV 1 (ppFEV 1 ) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV 1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV 1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all). These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT01531673).

Nuevos fenómenos en erupciones cometarias

NASA Astrophysics Data System (ADS)

Silva, A.

Se discuten aquí tres procesos físicos novedosos encontrados en la actividad de cometas: 1) El rol de una distribución de granos de hielo como fuente extendida de H2O en la coma, 2) El efecto de una discontinuidad en el plasma cometario, llamada Cometopausa, sobre la excitación del radical OH , y 3) La actividad por erupciones a grandes distancias heliocéntricas (r > 5 AU). Con respecto a 1) y 2), se presentan modelos que ajustan bien con las observaciones. En cuanto a 3), se presentan explicaciones posibles al fenómeno, y se trata el interesante caso de Chirón 2060, basándose en observaciones propias tomadas desde el CASLEO y datos anteriores.

Peligros de deslizamientos [Landslide Hazards

USGS Publications Warehouse

,

2000-01-01

Deslizamientos, flujos de escombrera y desastres geológicos similares provenientes de volcanes ocurren alrededor del mundo. Cada año estos desastres causan billones de dólares en pérdidas y un sinnúmero de fatalidades y heridos. El primer paso para reducir los efectos dañinos causados por estos desastres es el conocimiento y educación acerca de ellos. El Servicio Geológico de los Estados Unidos se dedica a educar una gran cantidad de personas a través de información e investigaciones acerca de peligros geológicos. Este documento está publicado en inglés y español y puede ser reproducido de cualquier forma para fomentar su distribución.

A systematic review and meta-analysis on the longitudinal relationship between eating pathology and depression.

PubMed

Puccio, Francis; Fuller-Tyszkiewicz, Matthew; Ong, Deborah; Krug, Isabel

2016-05-01

Undertake a meta-analysis to provide a quantitative synthesis of longitudinal studies that assessed the direction of effects between eating pathology and depression. A second aim was to use meta-regression to account for heterogeneity in terms of study-level effect modifiers. A systematic review was conducted on 42 studies that assessed the longitudinal relationship between eating pathology and depression. Of these 42 studies, multilevel random-effects meta-analyses were conducted on 30 eligible studies. Meta-analysis results showed that eating pathology was a risk factor for depression (rm  = 0.13) and that depression was a risk factor for eating pathology (rm  = 0.16). Meta-regression analyses showed that these effects were significantly stronger for studies that operationalized eating pathology as an eating disorder diagnosis versus eating pathology symptoms, and for studies that operationalized the respective outcome measure as a categorical variable (e.g., a diagnosis of a disorder or where symptoms were "present"/"absent") versus a continuous measure. Results also showed that in relation to eating pathology type, the effect of an eating disorder diagnosis and bulimic symptoms on depression was significantly stronger for younger participants. Eating pathology and depression are concurrent risk factors for each other, suggesting that future research would benefit from identifying factors that are etiological to the development of both constructs. Llevar a cabo un meta-análisis para proporcionar una síntesis cuantitativa de los estudios longitudinales que evaluaron la dirección de los efectos entre la alimentación patológica y la depresión. Un segundo objetivo fue utilizar la meta-regresión para dar cuenta de la heterogeneidad en términos de modificadores del efecto a nivel de estudio. MÉTODO: Una revisión sistemática se llevó a cabo en 42 estudios que evaluaron la relación longitudinal entre la alimentación patológica y la depresión. De estos 42 estudios, se realizaron meta-análisis de multinivel de efectos aleatorios en 30 estudios elegibles. Los resultados del meta-análisis mostraron que la alimentación patológica era un factor de riesgo para depresión (rm=0.13) y que la depresión era un factor de riesgo para la alimentación patológica (rm=0.16). Los análisis de meta-regresión mostraron que estos efectos eran significativamente más fuertes para estudios que operacionalizaban la alimentación patológica como un diagnóstico de trastorno de la conducta alimentaria versus síntomas de alimentación patológica, y para los estudios que operacionalizaban la medida respectiva de resultado como una variable categórica (e.g., un diagnóstico de trastorno o cuando los síntomas estaban "presentes"/"ausentes") versus una medida continua. Los resultados mostraron que en relación al tipo de alimentación patológica, el efecto de un diagnóstico de trastorno de la conducta alimentaria y síntomas bulímicos en la depresión era significativamente más fuerte para participantes más jóvenes. DISCUSIÓN: La alimentación patológica y la depresión son factores de riesgo concurrentes uno para el otro, lo que sugiere que la investigación futura se beneficiaría de identificar factores que son etiológicos al desarrollo de ambos constructos. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016;49:439-454). © 2015 Wiley Periodicals, Inc.

Bases para la elaboracion de unidades didacticas de calidad en el area de ciencias (Fisica y Quimica 3 deg ESO)

NASA Astrophysics Data System (ADS)

Maccioni, Elena Lucia

Este Trabajo Fin de Master tiene como objeto, el estudio previo de la educacion de la ciencia en la actualidad y mas destacable, del diseno de las unidades didacticas segun las metodologias mas frecuentes aplicadas por los diferentes sistemas educativos en el area de las Ciencias teniendo en cuenta la importancia y el efecto de la psicologia del alumnado y todo ello como no puede ser de otro modo bajo el corse de la Legislacion aplicable, Estatal, Autonomica y europea. Con estos antecedentes, se extrae cuales son las preguntas que deben contestarse en la elaboracion de una unidad didactica de calidad en el contexto, generacional (edad y sexo), del Proyecto Educativo de Centro, y de la Programacion del Departamento, discutiendo y justificando cada uno de los apartados en que estructuradamente dividiremos dicha Unidad, con un formato manejable, util, y dinamico en el tiempo que sea un verdadero instrumento educativo de aula. Teniendo en cuenta estas premisas, se procede a hacer una recopilacion de una misma unidad didactica publicada por diferentes editoriales, elegidas no al azar, sino en funcion de su penetracion editorial en nuestros centros de ESO, siendo las elegidas (SM y Oxford). Las diferentes unidades seleccionadas son analizadas de forma critica, atendiendo a los criterios generales de calidad bajo parametros cientificos y normativos, concluyendo con la aportacion final que es la redaccion de unas pautas cientifico-pedagogicas, para redactar unidades didacticas de calidad en el area de la Ciencias, en concreto en la Asignatura de Fisica y Quimica de 3º de ESO.

Comportamiento dinámico de asteroides en la región 23 < a < 26 UA

NASA Astrophysics Data System (ADS)

López García, F.

Los Kuiper Belt Objects (KBOs) pueden ser una fuente de origen de los cometas de corto período. Muchos de los KBOs observados parecen provenir, al igual que el sistema Pluton-Charonte, de órbitas resonantes con Neptuno. Los Centauros son objetos que dinámicamente provienen de órbitas inestables cuyo semieje mayor se encuentra entre las órbitas de Júpiter y Neptuno. Pudiera ser que estos cuerpos fueron expulsados desde la región del cinturón de Kuiper y se encuentran en un proceso de ``scattering" debido a los efectos gravitacionales de los planetas gigantes. Su tiempo de vida dinámico es de algunos millones de años. La evolución orbital de los objetos trans-Neptunianos nos permite conocer su comportamiento anterior, por eso, es importante su relación dinámica con la evolución orbital de Neptuno. El objeto de este trabajo es estudiar el comportamiento dinámico de partículas test que se encuentran entre las resonancias 3:2 con Neptuno y 2:3 con Urano, las cuales comprenden una región de 2 UA aproximadamente. Los primeros resultados indican que la mayoría de los objetos ficticios son eyectados hacia la parte externa del Sistema Solar, mientras que sólo una parte pequeña del total de objetos estudiados, aproximadamente un 7%, son eyectados hacia la parte interna del Sistema Solar, y en algunos casos sus órbitas pueden cruzar la órbita de los planetas terrestres.

PubMed

Gómez, Luis Alberto; Montoya, Gladis; Rivera, Hernán Mauricio; Hernández, Juan Carlos

2017-04-01

Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV).Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV.Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad.Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus.Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.

Correctors of the Major Cystic Fibrosis Mutant Interact through Membrane-Spanning Domains.

PubMed

Laselva, Onofrio; Molinski, Steven; Casavola, Valeria; Bear, Christine E

2018-06-01

The most common cystic fibrosis causing mutation is deletion of phenylalanine at position 508 (F508del), a mutation that leads to protein misassembly with defective processing. Small molecule corrector compounds: VX-809 or Corr-4a (C4) partially restores processing of the major mutant. These two prototypical corrector compounds cause an additive effect on F508del/cystic fibrosis transmembrane conductance regulator (CFTR) processing, and hence were proposed to act through distinct mechanisms: VX-809 stabilizing the first membrane-spanning domain (MSD) 1, and C4 acting on the second half of the molecule [consisting of MSD2 and/or nucleotide binding domain (NBD) 2]. We confirmed the effect of VX-809 in enhancing the stability of MSD1 and showed that it also allosterically modulates MSD2 when coexpressed with MSD1. We showed for the first time that C4 stabilizes the second half of the CFTR protein through its action on MSD2. Given the allosteric effect of VX-809 on MSD2, we were prompted to test the hypothesis that the two correctors interact in the full-length mutant protein. We did see evidence supporting their interaction in the full-length F508del-CFTR protein bearing secondary mutations targeting domain:domain interfaces. Disruption of the MSD1:F508del-NBD1 interaction (R170G) prevented correction by both compounds, pointing to the importance of this interface in processing. On the other hand, stabilization of the MSD2:F508del-NBD1 interface (by introducing R1070W) led to a synergistic effect of the compound combination on the total abundance of both the immature and mature forms of the protein. Together, these findings suggest that the two correctors interact in stabilizing the complex of MSDs in F508del-CFTR. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Analisis experimental de la propagacion en redes de area corporal para la banda de ultra wideband. experimental characterization of the propagation in ultra wideband body area networks

NASA Astrophysics Data System (ADS)

Garcia Serna, Ruben Gregorio

Diferentes dispositivos capaces de obtener informacion sobre parametros fisiologicos, cinematicos o contextuales del cuerpo pueden interconectarse de manera inalambrica dando lugar a las denominadas Redes de Area Corporal Inalambricas (WBAN, Wireless Body Area Networks). De entre las posibles tecnologias para establecer los enlaces, Ultra Wideband (UWB) esta captando cada vez un mayor interes debido a caracteristicas tales como el bajo nivel de potencia de transmision requerido (bajo nivel de exposicion a campos electromagneticos), el alto ancho de banda disponible y la alta resolucion temporal/espacial. El diseno de sistemas centrados en el cuerpo requiere de modelos de canal que describan de manera precisa la propagacion de senales en este tipo de entornos. Esta tesis se plantea con el objetivo de contribuir al estudio experimental de la propagacion en sistemas centrados en el cuerpo operando en la banda UWB. En primer lugar, se presenta un marco introductorio a las redes WBAN, sus elementos constitutivos, bandas de frecuencia, estandarizacion y modelos de canal. Ademas, se introducen los fundamentos de la tecnologia UWB y sus aplicaciones en este area. Seguidamente, se analiza en terminos de las perdidas de propagacion y la dispersion de retardo la propagacion en el canal off-body entre un transmisor fijo y un dispositivo receptor colocado sobre la superficie del cuerpo de un sujeto. Se considera la influencia de diferentes aspectos, tales como el entorno de medidas, la posicion de colocacion de una antena sobre el cuerpo y la postura adoptada por un sujeto. Finalmente, se analiza el canal de propagacion in-body considerando el movimiento relativo entre dos dispositivos causado por efecto de la respiracion. Las condiciones de propagacion en el interior del cuerpo se emulan por medio de un phantom liquido para UWB y la caracterizacion se plantea tanto en frecuencia, en terminos del modelado de la forma y el ensanchamiento del espectro Doppler, como en tiempo, por medio del estudio de la funcion de autocorrelacion y el tiempo de coherencia del canal.

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

NASA Astrophysics Data System (ADS)

Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

2010-12-01

Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

Relaciones entre el sueño y la adicción

PubMed Central

Cañellas, Francesca; de Lecea, Luis

2016-01-01

Resumen La interacción entre los trastornos del sueño y el abuso de sustancias es ya conocida, pero seguramente más compleja de lo que se pensaba. Existe tanto una relación positiva entre tener un trastorno por uso de substancias y sufrir un trastorno de sueño, como viceversa. Los efectos sobre el sueño dependen de la substancia utilizada, pero se ha demostrado que tanto durante su uso como en período de abstinencia los consumidores tienen diferentes problemas de sueño y fundamentalmente un sueño más fragmentado. Sabemos que hay que tener en cuenta los problemas de sueño para evitar recaídas en la adicción. Investigaciones recientes indican que el sistema hipocretinérgico definido por el neuropéptido hipocretina/orexina (Hcrt/ox), localizado en el hipotálamo lateral e implicado entre otros en la regulación del ciclo sueño-vigilia, jugaría un papel importante en las conductas adictivas. Diferentes estudios han demostrado interacciones entre el sistema hipocretinérgico, los circuitos de respuesta aguda al estrés y los sistemas de recompensa. También sabemos que la activación optogenética selectiva del sistema hipocretinérgico incrementa la probabilidad de la transición del sueño a la vigilia, y también es suficiente para iniciar un comportamiento compulsivo de recaída adictiva. La activación del sistema hipocretinérgico podría explicar la hipervigilia asociada al estrés y a la adicción. El mayor conocimiento de esta interacción permitiría entender mejor los mecanismos de la adicción y encontrar nuevas estrategias para el tratamiento de las adicciones. PMID:23241715

Neurobiología del autismo y TDAH mediante técnicas de neuroimagen: divergencias y convergencias

PubMed Central

Proal, Erika; Olvera, Jorge González; Blancas, Aurea S.; Chalita, Pablo J.; Castellanos, F. Xavier

2013-01-01

En el área clínica algunos síntomas del trastorno por déficit de atención e hiperactividad (TDAH), se presentan en los pacientes con trastorno del espectro autista (TEA). Se ha demostrado que existen alteraciones en circuitos cerebrales que impactan en fallas cognitivas y de comportamiento específicas de cada uno de estos trastornos. Sin embargo, han sido poco estudiados los correlatos cerebrales que hay detrás tanto de las similitudes como de las diferencias sintomatológicas. En la presente revisión se analizaron los estudios meta-analíticos existentes estructurales y funcionales en TDAH y TEA. Por un lado, se observaron convergencias en circuitos como el dorsal atencional, de funciones ejecutivas, visual, somatomotor y circuito de activación por defecto. Estas similitudes posiblemente explican las manifestaciones comórbidas entre los trastornos como la falla en la integración de información, motricidad fina y procesos atencionales específicos. Por otro lado, específicamente en el TDAH se observan déficits en el circuito de recompensa y ventral atencional, sistemas involucrados en la medición de efectos de reforzamiento y monitoreo atencional. En TEA los circuitos más afectados fueron los implicados en procesos de cognición social y lenguaje. En conclusión, existen correlatos neuronales en TEA que explican las manifestaciones clínicas tanto convergentes como divergentes presentes en TDAH. PMID:23897144

Dinámica y crecimiento de los granos de polvo en la nebulosa protoplanetaria

NASA Astrophysics Data System (ADS)

de La Fuente Marcos, Carlos

2001-06-01

En el escenario estándar de la formación planetaria, los planetesimales (cuerpos de tamaño kilométrico) crecen a partir de granos de polvo, similares a los interestelares, embebidos en un disco gaseoso denominado nebulosa protoplanetaria. Durante esta etapa, los movimientos del gas pueden tener gran influencia en la dinámica y el crecimiento de los granos de polvo, dado que el flujo kepleriano del gas frena el movimiento de los mismos haciendo que caigan hacia el Sol, y la turbulencia inhibe la inestabilidad gravitacional de la capa de polvo. Aunque se acepta que los planetesimales fueron los elementos constituyentes de los planetas, todavía se desconoce cómo se produjo la formación de los mismos. Por esta razón, en los estudios más recientes, existe un renovado interés por comprender mejor la evolución de la capa de polvo inmersa en el disco gaseoso de la Nebulosa. El gas que fluye en el disco puede engendrar estructuras carentes de simetría axial, como por ejemplo ondas espirales y vórtices, a partir de gran variedad de mecanismos de excitación e inestabilidad. En 1995, Barge y Sommeria pusieron de manifiesto que la existencia de vórtices gaseosos persistentes en la nebulosa solar tendría importantes consecuencias sobre la formación de los planetesimales y el posterior crecimiento de los planetas gigantes. La investigación desarrollada en esta Tesis analiza la relación entre el polvo y el gas debida al acoplamiento por fricción dinámica entre ambos; en concreto, se estudia el efecto del flujo medio del gas sobre la dinámica de las partículas de polvo. El primer objetivo es investigar en profundidad los procesos de captura y crecimiento de los granos de polvo dentro de un vórtice y su posible relevancia en cuanto a la formación de los planetesimales. El segundo objetivo es la exploración de los efectos de ondas espirales propagándose en el disco gaseoso sobre la dinámica y el crecimiento de las partículas. La presencia de líneas de corriente no circulares perturba significativamente el movimiento de las partículas alrededor del Sol e incrementa su vida media en la Nebulosa. El flujo medio del gas se modela de forma simple, analizándose la dinámica y el crecimiento de las partículas mediante simulaciones numéricas. Al incrementarse la vida media y la densidad superficial de las partículas sólidas, los mecanismos de confinamiento derivados de la presencia de vórtices y ondas espirales actuan sobre el material sólido de la Nebulosa (mediante agregación colisional o inestabilidades gravitacionales) de manera mucho más eficiente que la previamente considerada. Esto ofrece nuevas posibilidades para la formación de planetesimales y núcleos de planetas gigantes, y puede explicar la formación rápida de planetas extrasolares gigantes. Además, esta Tesis analiza la respuesta de las partículas, en un disco protoplanetario con un radio de 100 UA en torno a una estrella de tipo solar, al campo gravitatorio derivado de la presencia de dos estrellas compañeras ligadas en una órbita relativamente elongada (300-1600 UA). Para llevar a cabo este análisis, se han realizado una serie de simulaciones numéricas de configuraciones jerárquicas coplanares utilizando un programa FORTRAN que integra directamente las ecuaciones del movimiento con el objeto de modelar la presencia de las fuerzas gravitacionales y viscosas. El disco protoplanetario masivo se encuentra en torno a una de las componentes de la binaria. La evolución temporal del subdisco de polvo depende directamente de la naturaleza (directa o retrógrada) de la revolución relativa de la compañera estelar, y de la temperatura y la masa del disco circunestelar.

Seguridad del paciente en Radioterapia Intraoperatoria: Impacto de los elementos controlados por el Radiofisico

NASA Astrophysics Data System (ADS)

Tarjuelo, Juan Lopez

Introduccion: En la administracion de la radioterapia intervienen profesionales y equipos de tratamiento, por lo que existe el riesgo de error y se precisa que dicho equipamiento funcione conforme a lo esperado. A los radiofisicos les corresponde participar en las actividades de garantia o aseguramiento de la calidad, incluyendo el control de calidad de los equipos, y en la evaluacion de los riesgos asociados. La radioterapia intraoperatoria (RIO) es una tecnica radioterapica de intensificacion de dosis, altamente selectiva, dirigida a volumenes anatomicos restringidos durante el tratamiento quirurgico oncologico, basada en la administracion de una dosis absorbida alta por medio de un haz de electrones tras el examen visual directo del lecho tumoral. Como incorporar los ultimos avances en el refuerzo de la seguridad en radioterapia es una tarea ambiciosa y compleja, resulta mas concreta y de inmediata aplicacion su introduccion en la RIO. El objetivo es analizar los elementos que reducen los riesgos y aumentan la seguridad en la RIO y su dosimetria, y valorar la funcion del radiofisico en esta labor. Material y metodos: Se emplearon el planificador Radiance de GMV y el acelerador lineal de los tratamientos de RIO Elekta Precise, controlado con el verificador diario de haces Daily QA Check 1090 y medido con las camaras de ionizacion PPC 40, FC65-G y FC65-P de PTW-Freiburg, a su vez verificadas con fuentes radiactivas adecuadas de estroncio-90 modelos CDP y CDC de IBA Dosimetry. Se realizo un analisis de modos de fallo y efectos (failure mode and effect analysis, FMEA) con el fin de identificar los elementos que forman la RIO y aplicar las herramientas necesarias para la minimizacion de los riesgos y la mejora de la seguridad en la tecnica. Se estudiaron las verificaciones diarias de dicho acelerador Precise con el control estadistico de procesos (statistical process control, SPC) y se simularon intervenciones para devolverlo al estado llamado en control. El SPC tambien se uso para estudiar la estabilidad de las camaras de ionizacion mencionadas. Se realizo la dosimetria in vivo en 45 pacientes con MOSFET reforzados mobile TN-502RDM-H, pelicula radiocromica Gafchromic MD-55-2, y se elaboro un modelo teorico para explicar los datos. Por ultimo, al precisarse el uso en RIO de la simulacion virtual y del calculo de la dosis absorbida en el paciente virtual, se ha ilustrado este apartado con la aceptacion y el estado de referencia inicial del planificador de tratamientos modulados con calculo de Monte Carlo Elekta Monaco. Para ello se utilizaron la camara de ionizacion TW31016-0104 y la matriz seven29 de PTW-Freiburg, pelicula radiocromica Gafchromic EBT-2, y diferentes maniquies. Resultados: El FMEA identifico 57 modos de fallo y efectos potenciales. No se experimentaron sucesos relativos a una administracion inadecuada de la dosis absorbida. Se identificaron las revisiones dobles y por un par como claves para reducir los riesgos asociados al equipo de profesionales involucrado en la RIO. Se identificaron tambien oportunidades de mejora con el uso de la automatizacion y el enclavamiento. En cuanto al SPC, los indices de capacidad del proceso abarcaron de 1,6 a 9,3 para un nivel de especificaciones del +/-2%. Las intervenciones simuladas alcanzaron del 2% al 34% de las sesiones de medida. Las camaras de ionizacion Farmer derivaron en direcciones opuestas en un periodo de 6 anos; aunque ello no se aprecio en los informes de calibracion del laboratorio acreditado. No derivo la camara PPC-40. En la dosimetria in vivo, las medidas de los MOSFET no se desviaron significativamente de las medidas con pelicula. Los valores centrales de las dosis absorbidas quedaron entre la dosis absorbida prescrita y la maxima, con lo que indicaron un tratamiento correcto del lecho tumoral. Las anchuras de los intervalos de confianza de las dosis absorbidas esperadas segun el modelo teorico al nivel del 95% abarcaron del 8,6% al 14,7%. Las verificaciones de Monaco resultaron satisfactorias excepto en el caso de la transferencia de datos, que obligo a cambiar el flujo de trabajo. Conclusiones: El FMEA es crucial para priorizar las intervenciones reductoras del riesgo. Tipos diferentes de procesos fallidos se pueden eliminar o paliar con tipos diferentes de tales intervenciones. El SPC puede evaluar la variabilidad inherente del procedimiento monitorizador de haces de electrones, indica cuando intervenir para devolver un proceso al estado de control y si un proceso es capaz con respecto a unas especificaciones o requisitos establecidos. Es viable realizar dosimetria in vivo con un acelerador convencional fijo y obtener resultados satisfactorios en cada localizacion estudiada a pesar de su variabilidad. El modelo teorico desarrollado puede describir con exito resultados globales, aunque no puede explicar todos los datos experimentales. Se ha mostrado que un planificador puede funcionar correctamente en condiciones de laboratorio o trabajando solo; pero puede fallar cuando se conecta con otros equipos de radioterapia. Todos estos aspectos presentados y evaluados aqui constituyen competencias actuales o futuras, y deseables, de los radiofisicos, tanto en el campo de la RIO como en la extension a la radioterapia en su conjunto.

Modeling of adipose/blood partition coefficient for environmental chemicals.

PubMed

Papadaki, K C; Karakitsios, S P; Sarigiannis, D A

2017-12-01

A Quantitative Structure Activity Relationship (QSAR) model was developed in order to predict the adipose/blood partition coefficient of environmental chemical compounds. The first step of QSAR modeling was the collection of inputs. Input data included the experimental values of adipose/blood partition coefficient and two sets of molecular descriptors for 67 organic chemical compounds; a) the descriptors from Linear Free Energy Relationship (LFER) and b) the PaDEL descriptors. The datasets were split to training and prediction set and were analysed using two statistical methods; Genetic Algorithm based Multiple Linear Regression (GA-MLR) and Artificial Neural Networks (ANN). The models with LFER and PaDEL descriptors, coupled with ANN, produced satisfying performance results. The fitting performance (R 2 ) of the models, using LFER and PaDEL descriptors, was 0.94 and 0.96, respectively. The Applicability Domain (AD) of the models was assessed and then the models were applied to a large number of chemical compounds with unknown values of adipose/blood partition coefficient. In conclusion, the proposed models were checked for fitting, validity and applicability. It was demonstrated that they are stable, reliable and capable to predict the values of adipose/blood partition coefficient of "data poor" chemical compounds that fall within the applicability domain. Copyright © 2017. Published by Elsevier Ltd.

Calcium supplementation for reducing weight in people with obesity; an overview of systematic reviews

PubMed

Aguilera Eguía, Raúl; Jorquera Pino, Paula Jessica; Salgado, Claudia Jaqueline; Flores, Cherie

2016-09-20

Introducción: actualmente la obesidad es considerada un problema de salud pública, y en la mayor parte de los países ha evolucionado como una pandemia, presentando un incremento en su prevalencia y severidad.Objetivo:resumir las revisiones sistemáticas Cochrane y no Cochrane que evalúen el efecto de la suplementación de calcio en la disminución de grasa corporal en personas obesas.Materiales y métodos: se realizó una búsqueda en la base de datos Medline (1980-septiembre 2015), Metabuscador TripDatabase y Epistemonikos (hasta septiembre 2015), Cochrane BVS (hasta septiembre 2015), se buscó de forma manual en revistas relacionadas con el tema de interés, en actas de congresos, se realizó seguimiento de referencias relevantes y se contactó con expertos en el área.Resultados: la búsqueda preliminar arrojó un total de 7.163 artículos potencialmente elegibles, según los criterios de elegibilidad incluimos 2 revisiones sistemáticas de estudios clínicos aleatorizados.Conclusión: el suplemento de calcio al parecer sería efectivo en la disminución de grasa corporal, DM -0,51 (-1,27, 0,25); (p = 0,19), presentando "baja evidencia" según la metodología GRADE, esto quiere decir que "es muy probable que investigaciones adicionales tengan un impacto importante en la confianza de la estimación del efecto y es probable que cambie".

ATMOSPHERIC VOLATILE ORGANIC COMPOUND MEASUREMENTS DURING THE 1996 PASO DEL NORTE OZONE STUDY

EPA Science Inventory

Ambient air VOC samples were collected at surface air quality monitoring sites, near sources of interest, and aloft on the US (El Paso) and Mexican (Ciudad Juarez) side of the border during a six-week period of the 1996 Paso del Norte Ozone Study. Samples were collected at five...

Summary of a Gas Transport Tracer Test in the Deep Cerros Del Rio Basalts, Mesita del Buey, Los Alamos NM.

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

Stauffer, Philip H.; Rahn, Thomas A.; Ortiz, John Philip

Here we describe results from a tracer test in the Cerros del Rio basalt beneath Mesita del Buey, Technical Area 54 (TA-54) at Los Alamos National Laboratory (LANL or the Laboratory). This report follows from plans outlined in our previous Tracer Test Work Plan (LANL 2016). These activities were conducted by LANL to further characterize subsurface properties of the Cerros del Rio basalts at Material Disposal Area (MDA) L (Figure 1.1-1). The work presented follows from the “Interim Measures Work Plan for Soil-Vapor Extraction of Volatile Organic Compounds from Material Disposal Area L, Technical Area 54, Revision 1,” submitted tomore » the New Mexico Environment Department (NMED) in September 2014 (LANL 2014). Remediation of the MDA L vapor plume by soil-vapor extraction (SVE) is recommended as part of the final remedy in the “Corrective Measures Evaluation Report for Material Disposal Area L, Solid Waste Management Unit 54-006, at Technical Area 54, Revision 2” to meet a remedial action objective of preventing groundwater from being impacted above a regulatory standard by the transport of volatile organic compounds (VOCs) to groundwater through soil vapor (LANL 2011).« less

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

PubMed

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-08-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR

PubMed Central

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-01-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. PMID:26171232

Probing Conformational Rescue Induced by a Chemical Corrector of F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutant*

PubMed Central

Yu, Wilson; Chiaw, Patrick Kim; Bear, Christine E.

2011-01-01

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause loss of function of the CFTR channel on the apical surface of epithelial cells. The major CF-causing mutation, F508del-CFTR, is misfolded, retained in the endoplasmic reticulum, and degraded. Small molecule corrector compounds have been identified using high throughput screens, which partially rescue the trafficking defect of F508del-CFTR, allowing a fraction of the mutant protein to escape endoplasmic reticulum retention and traffic to the plasma membrane, where it exhibits partial function as a cAMP-regulated chloride channel. A subset of such corrector compounds binds directly to the mutant protein, prompting the hypothesis that they rescue the biosynthetic defect by inducing improved protein conformation. We tested this hypothesis directly by evaluating the consequences of a corrector compound on the conformation of each nucleotide binding domain (NBD) in the context of the full-length mutant protein in limited proteolytic digest studies. Interestingly, we found that VRT-325 was capable of partially restoring compactness in NBD1. However, VRT-325 had no detectable effect on the conformation of the second half of the molecule. In comparison, ablation of the di-arginine sequence, R553XR555 (F508del-KXK-CFTR), modified protease susceptibility of NBD1, NBD2, and the full-length protein. Singly, each intervention led to a partial correction of the processing defect. Together, these interventions restored processing of F508del-CFTR to near wild type. Importantly, however, a defect in NBD1 conformation persisted, as did a defect in channel activation after the combined interventions. Importantly, this defect in channel activation can be fully corrected by the addition of the potentiator, VX-770. PMID:21602569

Regulación del flujo sanguíneo uterino. II. Funciones de estrógeno y receptores estrogénicos α/β en acciones genómicas y no-genómicas del endotelio uterino *

PubMed Central

Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

2015-01-01

Resumen El embarazo está marcado por cambios y adaptaciones cardiovasculares que son importantes para el crecimiento y mantenimiento de la placenta y el feto. Durante este periodo, las adaptaciones vasculares uterinas manifiestan cambios clasificados como de corto o largo plazo los cuales están relacionados con adaptaciones vasodilatadoras, angiogénicas o de remodelación. El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsables por facilitar el incremento dramático en el fluido sanguíneo uterino necesario durante el embarazo. En ésta revisión bibliográfica se discuten la base estructural para la diversidad y selectividad funcional de los REs por el estrógeno, el papel de los REs sobre los efectos genómicos y no-genómicos en células endoteliales de arterias uterinas (CEAU). Estos temas integran el conocimiento científico sobre la regulación molecular de CEAU para mantener el incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113751

Abordaje a la Cisterna Ambiens

PubMed Central

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

2016-01-01

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

Measurement and evaluation of national family planning programs.

PubMed

Mauldin, W P

1967-03-01

RESUMEN: En los últimos quince años diez paises han inaugurado programas nacionales de planeamiento familiar: India, Pakistán, Corea del Sur, Taiwan, Turquía, Malasia, Ceilán, Túez, la República Arabe Unida, y Marruecos. Otros paises, incluyendo Tailandia, Hong Kong, Singapur, Kenya, Barbados, Trinidad y los Estados Unidos, apoyan y/o estimulan actividades de planeamiento familiar. En la mayor parte de los casos la razón fundamental del programa ha sido que si la tasa de crecimiento poblacional disminuyera, aumentaría la tasa de crecimiento económico.Las metas de largo alcance, expresadas típicamente en términos de reducir las tasa.de de natalidad o de crecimiento, tienen su ejemplo en el propósito de Pakistán de reducir su tasa de crecimiento a 26 para 1970; el de Corea de reducir su tasa de natalidad a 20 para 1971; y el de India de reducir su tasa de natalidad a 25 para 1973.Los objectivos intermedios, que cubren diversos aspectos del pro grama, incluyen metas específicas para un determinado mes a año, considerando personal, la adquisición de anticonceptivos, y el número de usarios por método. Las metas específicas anuales de aceptantes de dispositivos intrauterinos (IUD), para Taiwán, Corea, Túnez, Pakistán e India, son comunes, tanto por la naturaleza del artefacto, como por la facilidad de medición de los que continúan utilizándolos. El programa de evaluación en Taiwán, que trata de medir por diversos medios los efectos inmediatos, mediatos y de largo plazo del programa de planeamiento familiar sirve de modelo. El propósito de la evaiuación de un programa de planeamiento familiar es contribuir a la efectividad y eficiencia del programa, midiendo y analizando su progreso. Las áreas a medir pueden ser clasificadas como- (1) conocimiento acerca de; (2) actitudes hacia; (3) práctica de control de natalidad; y (4) nivel de fecundidad.Un buen sistema de evaluación debería incluir: A. Un buen conjunto de estadísticas de servicio presentadas en formularios estandarizados, en las siguienies formas: 1. Informes nensuales por áreas administrativas, sobre los actuales servicios de planeamiento familiar proporcionados en la actualidad, de carácter permanente o de larga duración (al presente, esterilización y IUD de acuerdo a las siguientes características del receptor: residencia, edad, paridad (número de hijos vivos por sexo), y donde se enteró del programa, si es posible "clase";(probablemente educación de la madre, pero posiblemente ocupación del esposo, ingreso, o equivalente); prácticas anticonceptivas anteriores; intervalo; y deseo de tener más hijos. En un programa grande estos datos pueden obtenerse en base a una muestra. 2. Informes mensuales sobre la distribución de suministros anticonceptivos (condones, píldoras, sustancias efervescentes, etc.), los primeros suministros deben ir acompañados de un registro de las características del recipiente, como anteriormente; los suministros subsecuentes se regietrarán sólo en volumen bruto. Esto también se aplicará al ritmo, donde éste método se enseñe a un número considerable de mujeres. 3. Informes regulares sobre las actividades de planeamiento familiar de médicos privados, como una estimación del efecto catalítico del programa del gobierno sobre ci sector privado. 4. Datos generates mensuales, ppr áreas admirtistrativas importantes, sabre: visitas domiciliarias, reuniones, cuñas radiates y televisadas, avisos en los periódicos y personal que trabaja. 5. Para propósitos de seguimiento una entrevi eta de campo cada 6 a 12 meses a cada N mujer de las listas para (1) y (2) arriba, en un total de 300 o 400, para conocer las tasas de continuación y las razones de abandono (ej: desea otro hijo, insatisfecha can ci método, otras). Las mue.stras podrían ser de 300 cada una, con una supuesta experiencia de 6, 12, 18 y 24 meses. B. Un buen conjunto de datos sobre costa (datos sobre cotos actulaes atribuíbles directamente al programa de planeamiento familiar) fraccionados par áreas principales y cinco a seis categorías de costos importantes tales coma: adminietración, personal de campo, publicidad, suministros, etc. C. Un buen conjunto de dates globales sobre la distribución de los suministros comerciales que puedan llegar tan cerca como sea posible del último consumidor, to cual significa probablemente obtener información de los mayoristas. D. Una encuesta de conocimientos, actitudes y prácticas (KAP) para una evaluación general cada dos años. Las preguntas básicas (además de las antes mencionadas y estatus marital y étnico cuando sea pertinente) son: actitud hacia e interés por la anticoncepción, número de niños por sexo, deseo de tener más hijos, prácticas anticonceptivas, experiencia sobre abortos, tal vez historia de embarazo (especialmente si esta producirá una tasa de fecundidad válida), aprobación del programa gubernamental (para uso politico), y si está actualmente embarazada (la única y mejor pregunta cuya respuesta habla del efecto sobre la tasa de natalidad). Administrativamente, la responsabilidad por la evalucion debe estar cerca al director, se debe tomar provisiones para obtener informes regulares (meneulaes) y especiales dirigidos a preguntar sobre política. El corolario es que el jefe de evaluación debe tener la confianza del director y debe estar al día en cuanto a las decisiones sabre la politics a seguir. Su trabajo consiste en extractar los aspectos principales que funcionan bien y los no operantes. En cuanto a costos, la evaluación debe hacerse sobre no más del 10 par ciento del costa del programa en paises pequeños (de menos de 30 milliones) y sabre no más del 5 per ciento en paises más grandes.Para medir en que forma el programa satisface el criterio final-la magnitud en que cambia la fecundidad-se debe realizar un trabajo más elaborado en el centro (Universidades, Consejos de población, etc.) para desarrollar una forma (a formas) segura de traducir las estadísticas de servicio en práticas y tal vez aún datos sobre suministro comercial en datos sabre tasas de natalidad. Esto incluye, par ejemplo, los esfuerzos para consolidar observaciones coma "cinco años-mujer de usa de IUD, a 400 condones equivalen a la prevención de un nacimiento," y esfuerzos como los de Pakistán de calcular tasas coma "años de protección de una pareja contra el embarazo."In the belief that a decrease in the rate of population growth will increase economic development, more than ten countries have inaugurated family planning programs in the past fifteen years. To provide a model for measuring the immediate, intermediate, and long-term effects of any such program, the authors use the Taiwan evaluation.The model suggests that a good system of evaluation should include monthly statistics on (1) participants, who are grouped by characteristics; (2) the distribution of supplies, reported at first by the characteristics of recipients, but after by gross volume only; (3) family planning activities of private physicians to measure the catalytic effect on the private sector; (4) new contacts and amount of advertising in mass media; (5) costs broken down by areas and by cost categories; and (6) distribution of commercial supplies. In addition, the program should conduct 300-400 interviews every 6-12 months to learn the rates of continuation and the rates and reasons for discontinuation. Finally, a KAP survey should be conducted every two years.The administration of the evaluation should be close to the director for policy decisions and for the ultimate work of evaluation-the finding of new ways to measure the main goal of change in fertility by the translation of statistics on Services provided and commercial supplies into birth rate data.

An Estimate of the Tidal Effects in the Dynamics of the Binary Galaxies

NASA Astrophysics Data System (ADS)

Junqueira, S.; de Freitas Pacheco, J. A.

1990-11-01

RESUMEN. Se ha estimado los efectos de marea en los pares dinamicos de galaxias elipticas. Para poder estudiar tales efectos hernos expandido el potencial gravitacional en potencias del cociente plr hasta en el orden 3 correspondientes a las fuerzas de marea. Hemos examina- do la influencia de este termino en el movimiento orbital. Se encon- tr6 el valor de M/LB = 10+7 (en unidades solares) para un ejemplo de 46 pares E-E usando Ia aproximaci6n de marea. De este resultado, no podemos concluir que existen alrededor de las galaxias halos grandes y obscuros. Hemos encontrado tambien que la suposici6n de masas puntuales es una buena aproximaci6n para el sistema fisico. Sin embargo, tal aproximaci6n sobreestima ligeramente el cociente masa-lurninosidad. ABSTRACT. In the present work we have estimated the tidal effects in the dynamics of pairs of elliptical galaxies. In order to study such effects we have expanded the gravitational potential in power of the ratio p/r up to order 3 corresponding to tidal forces. We examined the influence of this term in the orbital motion. The value of M/LB =lOi7 (in solar units) was found for a sample of 46 E-E pairs using the tidal approximation. From this result, we cannot conclude that large dark haloes exist around galaxies. We have also found that the assump- tion of point masses is a good approximation for the physical system. However, such an approximation overestimates slightly the mass-luminosity ratio. Keq wo't : GALAXIES-DYNAMICS

Expression of Neuronal and Inducible Nitric Oxide Synthase Isoforms and Generation of Protein Nitrotyrosine in Rat Brain Following Hypobaric Hypoxia

DTIC Science & Technology

2001-06-01

Promoci6n General del Conocimiento , Ministerio de Educaci6n y Cultura. We thank Mr. E. Sfnchez and directors and staff of the Hospital del Aire and CIMA... based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364: 626-632. Lowenstein, C.J

Novel Compound Heterozygous CLCNKB Gene Mutations (c.1755A>G/ c.848_850delTCT) Cause Classic Bartter Syndrome.

PubMed

Wang, Chunli; Chen, Ying; Zheng, Bixia; Zhu, Mengshu; Fan, Jia; Wang, Juejin; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

2018-02-14

Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother. Furthermore, we investigated the expression and protein trafficking change of c.848_850delTCT (TCT) and exon 15 deletion（E15）mutation in vitro. The E15 mutation markedly decreased the expression of ClC-Kb and resulted in a low-molecular-weight band (~55kD) trapping in the endoplasmic reticulum, while the TCT mutant only decreased the total and plasma membrane ClC-Kb protein expression but did not affect the subcellular localization. Finally, we studied the physiological functions of mutations by using whole-cell patch clamp and found that E15 or TCT mutation decreased the current of ClC-Kb/barttin channel. These results suggested that the compound defective mutations of CLCNKB gene are the molecular mechanism of the two cBS siblings.

Comportamiento del Helio en estrellas químicamente peculiares

NASA Astrophysics Data System (ADS)

Malaroda, S. M.; López García, Z.; Leone, F.; Catalano, F.

Las estrellas químicamente peculiares (CP) se caracterizan por tener deficiencias y sobreabundancias de algunos elementos químicos de hasta 106 veces la abundancia solar. Además presentan variaciones en las líneas espectrales. Se piensa que ello se debe a que los campos magnéticos presentes en este tipo de estrellas son principalmente dipolares, con un eje de simetría diferente del eje de rotación. La distribución de los elementos sobreabundantes y deficientes no es homogénea sobre la superficie estelar y las variaciones observadas serían una consecuencia directa de la rotación estelar. Entre los elementos con abundancia anómala se encuentra el Helio, cuyas líneas tienen intensidades que no son consistentes con una abundancia normal, que no puede ser determinada del modo usual, o sea, considerando una atmósfera con composición solar. Con el fin de determinar la abundancia de este elemento, se inició un estudio de estrellas anómalas de Helio, Hew y He strong. Además se determinarán las abundancias de otros elementos anómalos como ser el Si, Cr, Mg, Mn y Fe. Las mismas se determinan del modo tradicional, o sea: a) medida de los anchos equivalentes de las líneas de los distintos elementos analizados; b) adopción de la temperatura efectiva, gravedad y abundancia del Helio; c) cálculo del modelo de atmósfera d) comparación con las observaciones y reinicio de un proceso iterativo hasta lograr un acuerdo entre todos los parámetros analizados. Las observaciones se llevaron a cabo en el Complejo Astronómico El Leoncito. Se observaron setenta y ocho estrellas anómalas de Helio. En este momento se está procediendo a calcular las abundancias correspondientes a los distintos elementos químicos. Para ello se hace uso de los modelos de Kurucz, ATLAS9. Los cálculos NLTE de las líneas de Helio se llevan a cabo con el programa MULTI y se compararán con los realizados con el programa WIDTH9 de Kurucz (LTE), con el objeto de resaltar la importancia de los efectos NLTE.

Effects of Sterilizing Agents on Microorganisms

DTIC Science & Technology

1963-03-01

light increases with the incubation of Escherichia coli at 15, but the rate of in- 85. ESTUDIO DE LOS EFECTOS QUE PRODUCE duction of mutations...between the deoxyribonucleic acid content of a cell and its response to irradiation: 5-fluor- 86. ESTUDIO DE LOS EFECTOS QUE PRODUCE ouracil treated...EFFECTS OF ULTRAVIOLET LIGHT ON 84. ESTUDIO DE LOS EFECTOS QUE PRODUCE BACTERIA. III. ALTERATIONS IN THE LA LUZ ULTRAVIOLETA SOBRE LAS PHYSIOLOGICAL

[Analysis of MAT1A gene mutations in a child affected with simple hypermethioninemia].

PubMed

Sun, Yun; Ma, Dingyuan; Wang, Yanyun; Yang, Bin; Jiang, Tao

2017-02-10

To detect potential mutations of MAT1A gene in a child suspected with simple hypermethioninemia by MS/MS neonatal screening. Clinical data of the child was collected. Genomic DNA was extracted by a standard method and subjected to targeted sequencing using an Ion Ampliseq TM Inherited Disease Panel. Detected mutations were verified by Sanger sequencing. The child showed no clinical features except evaluated methionine. A novel compound mutation of the MAT1A gene, i.e., c.345delA and c.529C>T, was identified in the child. His father and mother were found to be heterozygous for the c.345delA mutation and c.529C>T mutation, respectively. The compound mutation c.345delA and c.529C>T of the MAT1A gene probably underlie the disease in the child. The semi-conductor sequencing has provided an important means for the diagnosis of hereditary diseases.

Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina.

PubMed

Nieva Moreno, María I; Zampini, Iris C; Ordóñez, Roxana M; Jaime, Gloria S; Vattuone, Marta A; Isla, María I

2005-11-16

This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of propolis extract from Amaicha del Valle, Tucumán, Argentina. The cytotoxicity assays carried out with the lethality test of Artemia salina revealed that the LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have antibiotic and antioxidant activities. Otherwise, for the testing doses, neither genotoxicity nor mutagenicity was found in any sample. The propolis extracts were able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o-phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively. From this result, the studied propolis may be inferred to contain some chemical compounds capable of inhibiting the mutagenicity of direct-acting and indirect-acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'-dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit the mutagenicity of NPD. Our results suggest a potential anticarcinogenic activity of Amaicha del Valle propolis and the chalcone isolated from it.

Iniciativas escolares y deportivas lideradas desde la Fédération Internationale de Football Association (FIFA): revisión sistemática.

PubMed

Correa, Jorge E; Meneses-Echávez, José F; Barengo, Noël C; Tovar, Gustavo; Ruiz-Castellanos, Erika; Lobelo, Felipe; Ramírez-Vélez, Robinson

2015-09-01

Introducción: Los programas iniciados por la Fédération Internationale de Football Association (FIFA) consisten en la difusión de mensajes relacionados con el cuidado de la salud y como estrategia de prevención de lesiones deportivas entre los niños y jóvenes. El objetivo de esta revisión sistemática fue resumir los resultados de la implementación de los programas "FIFA 11 para la salud" y "FIFA 11+". Métodos: Se realizó una búsqueda sistemática en las bases de datos electrónicos de MEDLINE, EMBASE y Scopus, identificando los estudios que evaluaran la implementación de los programas "FIFA 11 para la salud" y "FIFA 11+", durante los últimos 10 años (1 enero 2003 a 1 diciembre 2013). Resultados: Incluimos 17 estudios. Dos estudios evaluaron la implementación del programa "FIFA 11 para la salud" y encontraron un aumento significativo en el conocimiento de los mensajes de promoción de la salud; 15 estudios evaluaron los efectos del programa "FIFA 11+", reportando una reducción en el riesgo de lesiones deportivas y mejorías en el rendimiento deportivo. Discusión: Los programas "FIFA 11 para la salud" y "FIFA 11+" han demostrado resultados positivos para la salud, en el ámbito escolar y deportivo. Conclusiones: Dichos programas del FIFA representan una oportunidad para crear hábitos protectores y fomentar modos de vida saludables en niños y jóvenes.

Breakfast of champions or kiss of death? Survival and sexual performance of protein-fed, sterile Mediterranean fruit flies (Diptera: Tephritidae)

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

Yuval, B.; Maor, M.; Levy, K.

The sterile insect technique (SIT) is increasingly being used around the world to control Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), the Mediterranean fruit fly as part of an area-wide integrated approach. One option that may improve the effectiveness of the SIT, by increasing the sexual competitiveness of released sterile males, consists of feeding males protein during the post-teneral stage, a diet that increases sexual performance of wild males. We examine the effects of diet on the successive hurdles males must overcome in order to inseminate females, i.e., joining leks, copulating females, having their sperm stored and inhibition of female remating. Inmore » addition, we address the effects of diet on post-release foraging success, longevity, and the ability to withstand starvation. While protein feeding universally increases the sexual success of wild males, its effect on sterile males varies with strain, experimental settings, and environmental conditions. In some cases, treatments that resulted in the best sexual performance were significantly associated with increased vulnerability to starvation. However, no particular diet affected the ability of sterile males to find nutrients in the field when these where available. We suggest it may be better to release relatively short-lived flies that are highly competitive, rather than long-lived, sexually ineffective ones. (author) [Spanish] El uso de la tecnica de insecto esteril (TIE) esta aumentando alrededor del mundo para el control de Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), la mosca mediterranea de la fruta como parte de un enfoque integrado por toda el area. Una opcion que puede mejorar la eficiencia de TIE, por medio del aumento de la capacidad de los machos esteriles liberados para competir, consiste en la alimentacion de los machos con proteina durante la etapa de pos-teneral, una dieta que aumenta el desempeno sexual de los machos naturales. Nosotros examinamos los efectos de la dieta sobre los obstaculos sucesivos que los machos tienen que superar para inseminar las hembras, i.e., unir con otros machos en areas para el apareamiento, copula de las hembras, almacenar esperma e inhibir el re-apareamiento de hembras. Ademas discutimos los efectos de la dieta sobre el exito de su actividad forrajera despues de ser liberados, la longevidad y la habilidad para aguantar la inanicion. Mientras que la alimentacion con proteina universalmente aumentan el exito sexual de los machos naturales, su efecto sobre los machos esteriles varia segun la raza, el lugar de los experimentos y las condiciones ambientales. En algunos casos, los tratamientos que resultaron con mejor desempeno sexual fueron asociados significativamente con el aumento de la vulnerabilidad a la inanicion. Sin embargo, ninguna dieta en particular afecto la habilidad de los machos esteriles para encontrar nutrientes en el campo cuando fueron disponibles. Nosotros sugerimos que puede ser mejor el liberar moscas que tienen una vida relativamente corta y que son mas competidoras, en vez de moscas que tienen una vida larga y sexualmente inefectiva. (author)« less

ADIPOQUINAS EN EL NIÑO SANO Y AFECTO DE OBESIDAD

PubMed Central

Martos-Moreno, G.A.; Kopchick, J.J.; Argente, y J.

2015-01-01

El incremento universal de la prevalencia de obesidad en niños y adolescentes durante las últimas décadas, junto con la evidencia creciente de que el establecimiento de obesidad en etapas precoces de la vida está asociado con un incremento de la prevalencia de comorbilidades y del riesgo de muerte prematura, con gran repercusión económica en los sistemas sanitarios de los países occidentales, ha impulsado la investigación en este área. Estos estudios han remarcado la importante actividad endocrina del tejido adiposo, ejercida por medio de la síntesis y secreción de un gran número de péptidos y citoquinas, denominados adipoquinas. En esta revisión se resume el estado actual de los conocimientos, así como los estudios más relevantes, en relación con la dinámica de secreción de las principales adipoquinas en niños, centrándose en el control de la homeostasis energética, regulación metabólica (fundamentalmente, metabolismo de los hidratos de carbono) e inflamación. Asímismo, se analizan las particularidades de la síntesis, secreción y acciones de las adipoquinas desde el nacimiento hasta la adolescencia, reseñando el efecto que, sobre ellas, ejerce la instauración de la obesidad. PMID:23228441

Effects of pond draining on biodiversity and water quality of farm ponds.

PubMed

Usio, Nisikawa; Imada, Miho; Nakagawa, Megumi; Akasaka, Munemitsu; Takamura, Noriko

2013-12-01

Farm ponds have high conservation value because they contribute significantly to regional biodiversity and ecosystem services. In Japan pond draining is a traditional management method that is widely believed to improve water quality and eradicate invasive fish. In addition, fishing by means of pond draining has significant cultural value for local people, serving as a social event. However, there is a widespread belief that pond draining reduces freshwater biodiversity through the extirpation of aquatic animals, but scientific evaluation of the effectiveness of pond draining is lacking. We conducted a large-scale field study to evaluate the effects of pond draining on invasive animal control, water quality, and aquatic biodiversity relative to different pond-management practices, pond physicochemistry, and surrounding land use. The results of boosted regression-tree models and analyses of similarity showed that pond draining had little effect on invasive fish control, water quality, or aquatic biodiversity. Draining even facilitated the colonization of farm ponds by invasive red swamp crayfish (Procambarus clarkii), which in turn may have detrimental effects on the biodiversity and water quality of farm ponds. Our results highlight the need for reconsidering current pond management and developing management plans with respect to multifunctionality of such ponds. Efectos del Drenado de Estanques sobre la Biodiversidad y la Calidad del Agua en Estanques de Cultivo. © 2013 Society for Conservation Biology.

A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II.

PubMed

Yan, Xukun; Zhang, Tianyu; Wang, Zhengmin; Jiang, Yi; Chen, Yan; Wang, Hongyan; Ma, Duan; Wang, Lei; Li, Huawei

2011-12-20

Waardenburg syndrome type II (WS2) is associated with syndromic deafness. A subset of WS2, WS2A, accounting for approximately 15% of patients, is attributed to mutations in the microphthalmia-associated transcription factor (MITF) gene. We examined the genetic basis of WS2 in a large Chinese family. All 9 exons of the MITF gene, the single coding exon (exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA (mtDNA) 12S rRNA were sequenced. A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA] in exon 8 of the MITF gene co-segregates with WS2 in the family. The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids. The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+[235delC] compound heterozygous pathogenic mutation in the GJB2 gene. No pathogenic mutation was found in mtDNA 12S rRNA in this family. Thus, a novel compound heterozygous mutation, c.[742_743delAAinsT;746_747delCA] in MITF exon 8 was the key genetic reason for WS2 in this family, and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband. Copyright © 2011. Published by Elsevier Ltd.

[Not Available].

PubMed

Visiedo, Andrea; Sainz de Baranda, Pilar; Crone, Diane; Aznar, Susana; Pérez-Llamas, Francisca; Sánchez-Jiménez, Regina; Velázquez, Francisca; Berná-Serna, Juan de Dios; Zamora, Salvador

2016-07-19

Introducción y objetivos: en el presente trabajo se ha realizado una revisión sistemática durante los últimos 15 años de los estudios científicos que se han desarrollado con el objetivo de aumentar los niveles de actividad física, mejorar la salud y disminuir la prevalencia de sobrepeso y obesidad en escolares de entre 5 y 10 años.Material y métodos: se han encontrado un total de 28 estudios: 2 revisiones sistemáticas, 2 artículos descriptivos del proceso metodológico y 24 de intervención. Se pueden diferenciar dos tipos de intervenciones, por un lado aquellas intervenciones centradas en aumentar los niveles de actividad física, y por otro, aquellas que introducen además una parte de educación y valoración nutricional.Resultados: el análisis de los resultados muestra mejoras estadísticamente significativas en el 47,3% de las intervenciones que evaluaron el IMC, en el 44,4% de las que evaluaron la composición corporal, en el 40% de las que evaluaron el índice cintura-cadera, en el 50% de las que evaluaron el sumatorio de pliegues cutáneos. En relación con los efectos sobre la condición física, destacar que en el 45,4% de las intervenciones que avaluaron la resistencia cardiovascular se observaron mejoras significativas, al igual que en el 66,6% de las que analizaron los efectos sobre la fuerza. Finalmente, se observaron cambios en los hábitos alimentarios o en el conocimiento de los escolares en alimentación y nutrición en el 66,6% de los estudios que evaluaron dichos parámetros.

PubMed

Scotta, Ana Verónica; Bongiovanni, Guillermina Azucena; Soria, Elio Andrés

2018-03-21

Antecedentes: Clorpirifos es un pesticida altamente tóxico, que puede producir inmunotoxicidad con efectos deletéreos sobre la salud a nivel mundial. Por otro lado, las plantas americanas pueden tener derivados con actividad protectora e inmunoestimulante. Por lo tanto, debe evaluarse el potencial de estas plantas frente a clorpirifos. Objetivo: Identificar extractos acuosos bioactivos de Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQ), Peumus boldus (PB), e Ilex paraguariensis (IP), contra la toxicidad de clorpirifos sobre esplenocitos de hembras Balb/c. Materiales y Métodos: Esplenocitos fueron tratados in vitro por 72 horas con 0-35 µg/mL de clorpirifos, 0-100 µg/mL de cada extracto (LG, AQ, PB, IP) y 0-5 µg/mL de concanavalina A. Luego, se midió y analizó estadísticamente viabilidad y muerte celular (tinciones de resazurina y yoduro de propidio), hidroperóxidos, lipoperóxidos (ensayos basados en naranja de xilenol), actividad de la ?-glutamiltranspeptidasa (método de Szasz). Resultados: Clorpirifos redujo la viabilidad celular de forma dosis dependiente, lo que fue contrarrestado por AQ e IP, los que fueron menos activos en las células inducibles por concanavalina A (p<0,05). La toxicidad por clorpirifos implicó la inducción de la ?-glutamiltranspeptidasa con la consecuente reducción de los peróxidos, mientras que AQ y principalmente IP antagonizaron dichas respuestas (p<0,05). Conclusiones: Los extractos de Ilex paraguariensis y Aspidosperma quebracho-blanco protegieron in vitro a los esplenocitos frente a clorpirifos. Este efecto dependió del tipo celular, dado que las células inducibles por concanavalina A fueron más susceptibles a este tóxico.

Nanoparticulas basadas en complejos de Fe(II) con transicion de espin: sintesis, caracterizacion y aplicaciones en electronica molecular

NASA Astrophysics Data System (ADS)

Monrabal Capilla, Maria

Esta tesis doctoral esta organizada en 5 capitulos y esta destinada al estudio de sistemas de Fe (II) que presentan el fenomeno de la transicion de espin a escala nanometrica. El capitulo 1 contiene una introduccion general sobre materiales moleculares multifuncionales, destacando aquellos ejemplos mas importantes. Por otro lado, se explicara el fenomeno de la transicion de espin, tratando aspectos conceptuales, los antecedentes mas importantes y la situacion actual. En el capitulo 2 se describen los diferentes procesos existentes para la obtencion de diferentes tipos de nanoparticulas. Ademas, se presenta la sintesis y caracterizacion de nanoparticulas del polimero de coordinacion unidimensional [Fe(Htrz)2(trz)]BF4, obtenidas mediante el metodo de micelas inversas. Estas nanoparticulas, con una estrecha distribucion de tamanos centrada alrededor de los 11 nm, presentan una transicion de espin muy abrupta, con un ancho ciclo de histeresis termica de unos 40K. En el capitulo 3 se describe el proceso de modificacion del tamano de las nanoparticulas descritas en el capitulo anterior, llevado a cabo variando la proporcion de surfactante/H2O en el medio. Ademas, con el objetivo de modificar las propiedades magneticas de las nanoparticulas obtenidas en el capitulo 2, se lleva a cabo la sintesis de nanoparticulas de polimeros de la misma familia del [Fe(Htrz)2(trz)]BF4. En concreto se sintetizaron 3 nuevos tipos de nanoparticulas basadas en el polimero [Fe(Htrz)1-x(NH2trz)x](ClO4)2, siendo x = 0.05, 0.15 y 0.3, en cada caso. Estas nanoparticulas siguen presentando una estrecha distribucion de tamanos y una transicion de espin muy abrupta y con un ancho ciclo de histeresis. Ademas, se observa que este ciclo se desplaza a temperaturas mas proximas a la temperatura ambiente a medida que se aumenta el porcentaje de 4-amino-1, 2, 4- triazol en la muestra. Pero al mismo tiempo se produce una disminucion de la anchura de este ciclo. Por ultimo, en este capitulo se presenta la sintesis de otro nuevo tipo de nanoparticulas, obtenidas a partir de otro polimero de la misma familia, el [FeO8ZnO2(Htrz)3](BF4). Estas nanoparticulas se sintetizaron con el objetivo de estudiar el efecto de la dilucion del metal en la muestra. Como resultado se obtuvieron nanoparticulas que tambien presentan una estrecha distribucion de tamanos pero en este caso la transicion de espin no es tan abrupta como en los casos anteriores. Aunque sigue presentando un ciclo de histeresis termica bastante ancho y a temperaturas proximas a la temperatura ambiente. En el capitulo 4 se describiran las estrategias que se han seguido para mejorar la estabilidad y afinidad sobre diferentes sustratos de las nanoparticulas sintetizadas en el capitulo 2. Tambien se hablara de los intentos realizados parar depositarlas en superficies y embeberlas en diferentes matrices organicas e inorganicas. En el capitulo 5 presentaremos la obtencion de un interruptor molecular realizado poniendo en contacto nanoparticulas individuales sintetizadas en el capitulo 2, con unos electrodos separados varios nanometros. Este dispositivo exhibe "switching" y efecto memoria a temperaturas proximas a la temperatura ambiente como consecuencia de la biestabilidad intrinseca de las nanoparticulas. Ademas demostraremos que el estado magnetico de estas nanoparticulas puede ser controlado electricamente, ya que la transicion de espin en este nanodispositivo molecular puede ser inducida simplemente aplicando un voltaje, lo que puede ser de gran interes para la electronica molecular.

Role of the microbial population on the flavor of the soft-bodied cheese Torta del Casar.

PubMed

Ordiales, Elena; Martín, Alberto; Benito, María José; Hernández, Alejandro; Ruiz-Moyano, Santiago; Córdoba, María de Guía

2013-09-01

The purpose of this work was to investigate the influence of the spontaneous microbial population on the flavor of Torta del Casar cheese. A total of 16 batches of cheeses with different microbial qualities were used. Their physicochemical and microbial characteristics were evaluated during ripening and then related with the volatile compounds, taste, and flavor properties of the finished cheeses. Acids were the most abundant volatile compounds, followed by alcohols and carbonyls. The amount of acetic acid and several alcohols were linked to cheeses with higher counts of lactic acid bacteria (LAB), whereas Enterobacteriaceae counts were associated with semivolatile fatty acids. The gram-positive catalase-positive cocci counts were correlated with esters and methyl ketones. Although the role of the LAB in the flavor development of Torta del Casar is the most relevant, other microbial groups are necessary to impart the flavor of the cheese and to minimize the possible off-flavor derived from excessive concentrations of LAB metabolites, such as acetic acid. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of pre-irradiation conditioning of Medfly pupae (Diptera: Tephritidae): Hypoxia and quality of sterile males

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

Nestel, D.; Nemny-Lavy, E.; Islam, S.M.

Irradiation of pupae in sterile insect technique (SIT) projects is usually undertaken in hypoxic atmospheres, which have been shown to lessen the deleterious effects of irradiation on the quality of adult sterile flies. Although this is the accepted technology in most mass-rearing and sterilization facilities, to date no information has been generated on the actual levels of oxygen (O{sub 2}) in pupae-packing containers during irradiation. The present study utilized recently-developed technology to investigate the O{sub 2} level inside bags in which pupae of Mediterranean fruit fly (medfly) Ceratitis capitata (Wiedemann) are packed prior to irradiation, the ability of pupae tomore » create hypoxic environments in these bags, and the effect of O{sub 2} atmospheres on the quality of irradiated males. Pupae, 1 d before adult emergence, were shown to deplete the O{sub 2} level in sealed bags in approximately 1 h. The rate of O{sub 2} consumption was dependent upon pupal age and incubation temperature. Incubation temperature did not significantly affect the quality of pupae or mating capacity of resultant adult males if pupae were irradiated under maximal hypoxic conditions inside packing bags. In contrast, mating competitiveness drastically decreased when pupae were irradiated under ambient O{sub 2} conditions, with the packing bag open. There was no difference in the mating capacity of males when pupae were irradiated in sealed bags under either 10% or 2% O{sub 2} levels, or under maximal hypoxia. Normal doses of fluorescent dye, applied to pupae to mark sterile flies, did not affect the ability of pupae to create hypoxic conditions inside packing bags, nor the quality control parameters of either pupae or adults. Current practices in mass-rearing facilities are discussed in the light of these results. (author) [Spanish] La irradiacion de pupas en proyectos de mosca esteril usualmente se hace bajo condiciones de hipoxia. Esta condicion ha demostrado ser menos detrimente a la calidad de las moscas que la irradiacion en atmosferas con proporcion normal de oxigeno. Aunque esta ha sido por mucho tiempo parte del protocolo de irradiacion en plantas de produccion de mosca esteril, hasta ahora no se ha medido el contenido de oxigeno dentro de los recipientes de empaque de pupa durante la irradiacion. El presente estudio investigo los contenidos de O{sub 2} en los contenedores de pupas de la mosca de las frutas del Mediterraneo (Ceratitis capitata Wiedeman), la habilidad de pupas de crear hipoxia dentro de los contenedores, y los efectos del contenido de O{sub 2} durante la irradiacion del contenedor en la calidad y capacidad de apareamiento de moscas esteriles. Pupas de un dia antes de emerger como adultos crearon atmosferas de maxima hipoxia dentro del empaque en aproximadamente una hora. La proporcion de consumo de O{sub 2} en contenedores sellados es dependiente de la edad de la pupa, y de la temperatura de incubacion. La temperatura de incubacion no afecto significativamente la calidad ni la capacidad de apareamiento de machos derivados de pupas irradiadas bajo condiciones de hipoxia. Sin embargo, la capacidad de apareamiento de machos irradiados como pupas en contenedores abiertos y en condiciones oxigenadas fue drasticamente afectada. En comparacion a los resultados anteriores, atmosferas de 2% y 10% O{sub 2} durante la irradiacion no afectaron la capacidad de apareamiento de moscas esteriles. Polvo fluorescente, aplicado a pupas para marcar las moscas esteriles, no tuvo efectos sobre la capacidad de las pupas de crear hipoxia. Los resultados de este estudio se discuten en base a las practicas actuales de produccion e irradiacion. (author)« less

Colour Evaluation, Bioactive Compound Content, Phenolic Acid Profiles and in Vitro Biological Activity of Passerina del Frusinate White Wines: Influence of Pre-Fermentative Skin Contact Times.

PubMed

Carbone, Katya; Fiordiponti, Luciano

2016-07-22

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in vitro biological activity of monovarietal Passerina del Frusinate white wines and the effect of different maceration times (0, 18 and 24 h) were evaluated based on these parameters. Results highlighted statistically significant differences for almost all analysed parameters due to a strong influence of the pre-fermentative skin contact time. The flavan content of macerated wines was six times higher than that of the control, while total polyphenols were 1.5 times higher. According to their phytochemical content, macerated wines showed the highest antiradical capacity tested by means of DPPH(•) and ABTS(+•) assays. Besides, prolonged maceration resulted in a reduction of CIELab coordinates as well as of the content of phenolic substances and antiradical capacity. Among the phenolic acids analysed, the most abundant were vanillic acid and caffeic acid; the latter proved to be the most susceptible to degradation as a result of prolonged maceration. Passerina del Frusinate appears as a phenol-rich white wine with a strong antioxidant potential similar to that of red wines.

Rescuing mutant CFTR: a multi-task approach to a better outcome in treating cystic fibrosis.

PubMed

Amaral, Margarida D; Farinha, Carlos M

2013-01-01

Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients--F508del-CFTR. However, there is increasing evidence that to fully restore the multiple defects associated with F508del-CFTR, different small molecules with distinct corrective properties may be required. Towards this goal, a better insight into MoA of correctors is needed and several constraints should be addressed. The methodological approaches to achieve this include: 1) testing the combined effect of compounds with that of other (non-pharmacological) rescuing strategies (e.g., revertants or low temperature); 2) assessing effects in multiple cellular models (non-epithelial vs epithelial, non-human vs human, immortalized vs primary cultures, polarized vs non polarized, cells vs tissues); 3) assessing compound effects on isolated CFTR domains (e.g., compound binding by surface plasmon resonance, assessing effects on domain folding and aggregation); and finally 4) assessing compounds specificity in rescuing different CFTR mutants and other mutant proteins. These topics are reviewed and discussed here so as to provide a state-of-the art review on how to combine multiple ways of rescuing mutant CFTR to the ultimate benefit of CF patients.

La problematica de la demarcacion entre ciencia y pseudociencia y sus implicaciones en la educacion cientifica

NASA Astrophysics Data System (ADS)

Jimenez Tolentino, Dinorah

2011-12-01

En la sociedad prevalece una tendencia generalizada hacia la inclusion de creencias y practicas pseudocientificas. Esta investigacion responde a la necesidad de analizar como la proliferacion de las pseudociencias afecta la vision que tienen los estudiantes universitarios sobre las ciencias naturales. A tales efectos, la investigadora describe las concepciones epistemologicas que tienen los estudiantes sobre las ciencias y las pseudociencias e identifica los criterios de demarcacion, entre un area y otra, que se derivan de estas concepciones. De igual modo, esta identifica las creencias y practicas pseudocientificas de mayor arraigo entre los estudiantes, destacando, a su vez, la razon de ser de las mismas. Por ultimo, la investigadora analiza las implicaciones educativas de la problematica de la demarcacion entre ciencia y pseudociencia. La investigacion es de naturaleza mixta, enmarcada en los paradigmas empirico- analitico y cualitativo. El proceso investigativo se llevo a cabo mediante la administracion del cuestionario Criterios para la demarcacion entre ciencia y pseudociencia. La parte cualitativa estuvo enmarcada en el diseno de estudio de caso, recopilando informacion mediante entrevistas semiestructuradas en dos grupos focales. La poblacion de estudio estuvo constituida por estudiantes universitarios del nivel subgraduado de la Universidad Central de Bayamon. Los resultados del estudio reflejaron las concepciones erroneas de los estudiantes sobre la naturaleza de las ciencias y las pseudociencias. Con respecto a la demarcacion entre ciencia y pseudociencia, el criterio imperante entre los universitarios es el de la verificabilidad, considerando la aplicacion del metodo cientifico como el metodo para demostrar la veracidad de las teorias cientificas. Las creencias y practicas pseudocientificas no son muy frecuentes entre los universitarios. Estos atribuyen las mismas a la prevalencia de elementos supersticiosos y al engano a que es sometida la poblacion por quienes promueven estas practicas. A partir de los resultados, la investigadora concluye que la problematica sobre la demarcacion entre ciencia y pseudociencia esta influenciada por unos procesos de ensenanza enfocados en una vision distorsionada de la ciencia, producto de la no integracion de los aspectos filosoficos, historicos y sociales de la misma.

Effect of acclimation to outdoor condition on the sexual performance of mass-produced Medflies (Diptera: Tephritidae)

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

Pereira, R.; Silva, N.; Quintal, C.

Application of the sterile insect technique (SIT) as part of integrated area-wide programs to control the Mediterranean fruit fly (medfly) Ceratitis capitata (Wiedemann) require that the released males attract wild females and transfer sterile sperm. However, knowledge about male sexual performance after they are released is scarce. We conducted a study to evaluate male sexual performance in field cage tests, according to standard quality control procedures. Mass-reared 5-d-old sterile males from the genetic sexing strain VIENNA 7mix2000 were acclimated for 0, 1, and 3 d to outdoor conditions before competing with wild males for wild females. Although the proportion ofmore » mating (PM) in the test was satisfactory, the resulting relative sterility index (RSI) data showed no significant differences among the treatments. The data indicate that pre-conditioning males to outdoor conditions in Madeira did not confer an advantage in field cage sexual performance. (author) [Spanish] La aplicacion de la tecnica del insecto esteril (TIE) como parte de un programa integrado de amplio efecto para el control de la mosca mediterranea de la fruta Ceratitis capitata (Wiedemann) requiere que los machos liberados atraigan las hembras naturales y transfieran su esperma. Sin embargo, el conocimiento del desempeno sexual de los machos despues de ser liberados es muy escaso. Nosotros realizamos un estudio para evaluar el desempeno sexual de los machos en pruebas usando jaulas del campo, segun los procedimientos estandardizados de calidad. Machos esteriles de 5 dias de edad de la raza que separa los sexos geneticamente VIENNA 7mix2000 criados en masa fueron aclimatados por 0, 1 y 3 dias en condiciones de campo antes de competir con machos naturales para las hembras naturales. Aunque la proporcion del apareamiento en la prueba fue satisfactorio, el indice relativo de esterilidad (IRS) resultante no mostro ninguna diferencia significativa entre los tratamientos. Los datos indicaron que al condicionar los machos anteriormente a las condiciones de campo en Madeira no conferio ventaja alguna en el desempeno sexual en la jaula de campo. (author)« less

Efectos Especiales de Anclaje (Estudio sobre Regresiones de Juicios Condicionales). Parte 1: Distincion entre Efectos Aditivos y Efectos Multiplicativos en el Fenomeno de Anclaje (Special Effects of Anchoring (Study on Regression of Conditional Judgements) Part 1: Distinction Between Additive Effects and Multiplicative Effects in the Phenomenon of Anchoring). Publication No. 17.

ERIC Educational Resources Information Center

Lopez Alonso, A. O.

A linear relationship was found between judgements given by 160 subjects to 7 objects presented as single stimuli (alpha judgements) and judgements given to the same objects presented with a condition (gamma judgements). This relationship holds for alpha judgements and the gamma judgements that belong to a family of constant stimulus and varying…

[In Process Citation].

PubMed

Gonçalves Schemitt, Elizângela; Raskopf Colares, Josieli; Minuzzo Hartmann, Renata; Morgan-Martins, María Isabel; Marroni, Cláudio Augusto; Tuñón, M Jesús; Possa Marroni, Norma

2016-03-25

Introducción: la insuficiencia hepática fulminante (IHF) es un síndrome clínico poco frecuente, que se caracteriza por una disfunción hepática severa y repentina. La tioacetamida (TAA) es una hepatotoxina cuya administración puede inducir necrosis centrolobulillar en las células hepáticas y aumentar la formación de especies reactivas de oxígeno y la peroxidación lipídica en ratas. La glutamina es un precursor para la síntesis de glutatión. Objetivo: el objetivo del estudio es evaluar los efectos antioxidantes de la glutamina en un modelo de rata de IHF inducida por TAA. Métodos: ratas macho Wistar se dividieron en cuatro grupos de acuerdo con el tratamiento y el tiempo de evaluación: control, glutamina (25 mg/kg), tioacetamida (400 mg/kg) y tioacetamida más glutamina. Los animales se evaluaron después de 24, 36 y 48 horas. Se recogieron muestras de sangre para el análisis de los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), fosfatasa alcalina (AP), bilirrubina total (TB) y creatinina (CRE), y muestras de hígado para evaluar la peroxidación lipídica, las sustancias reactivas al ácido tiobarbitúrico (TBARS), la actividad de las enzimas antioxidantes superóxido dismutasa (SOD), glutatión peroxidasa (GPx), catalasa (CAT) y glutatión S-transferasa (GST). Además se midieron mediante inmunohistoquímica el factor nuclear kappa N (NF-κB), el fator de necrosis tumoral (TNF-α) y la óxido nítrico sintasa inducible (iNOS). Resultados: la TAA causó alteraciones en los parámetros bioquímicos e histológicos, y el aumento de los marcadores del proceso inflamatorio. Los niveles de TBARS y la actividad de SOD y GST fueron significativamente inferiores en los grupos de glutamina en comparación con TAA. La actividad de CAT se incrementó en los animales tratados con glutamina en comparación con la TAA. La actividad GPx también fue menor a las 36 y 48 h en los animales tratados com glutamina. El daño tisular y la expresión de NF-κB, TNF-α e iNOS fueron significativamente inferiores en los animales tratados con glutamina. Conclusión: la glutamina ha demostrado tener efectos protectores contra el daño hepático en un modelo de IHF inducida por TAA en la rata.

Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing

PubMed Central

Lo, David; Weng, Jingning; Liu, xiaohong; Yang, Juhua; He, Fen; Wang, Yun; Liu, Xuyang

2016-01-01

PURPOSE To detect the disease-causing gene in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP). METHODS All subjects in this family underwent a complete ophthalmic examination. Targeted-capture next generation sequencing (NGS) was performed on the proband to detect variants. All variants were verified in the remaining family members by PCR amplification and Sanger sequencing. RESULTS All the affected subjects in this pedigree were diagnosed with retinitis pigmentosa (RP). The compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations in the Crumbs homolog 1 (CRB1) gene were identified in all the affected patients but not in the unaffected individuals in this family. These mutations were inherited from their parents, respectively. CONCLUSION The novel compound heterozygous mutations in CRB1 were identified in a Chinese pedigree with ARRP using targeted-capture next generation sequencing. After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree. To the best of our knowledge, there is no previous report regarding the compound mutations. PMID:27806333

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

PubMed Central

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant. The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques on three distinct cellular models: (1) CFTR-expressing Chinese hamster ovary cells, (2) human airway Calu-3 epithelial cells and (3) human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated 125I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. 125I efflux and Cl− currents induced by octanol were blocked by glibenclamide but insensitive to 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, as expected for a CFTR Cl− current. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF. PMID:14967738

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels.

PubMed

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-03-01

1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

The role of agri-environment schemes in conservation and environmental management

PubMed Central

Batáry, Péter; Dicks, Lynn V; Kleijn, David; Sutherland, William J

2015-01-01

Over half of the European landscape is under agricultural management and has been for millennia. Many species and ecosystems of conservation concern in Europe depend on agricultural management and are showing ongoing declines. Agri-environment schemes (AES) are designed partly to address this. They are a major source of nature conservation funding within the European Union (EU) and the highest conservation expenditure in Europe. We reviewed the structure of current AES across Europe. Since a 2003 review questioned the overall effectiveness of AES for biodiversity, there has been a plethora of case studies and meta-analyses examining their effectiveness. Most syntheses demonstrate general increases in farmland biodiversity in response to AES, with the size of the effect depending on the structure and management of the surrounding landscape. This is important in the light of successive EU enlargement and ongoing reforms of AES. We examined the change in effect size over time by merging the data sets of 3 recent meta-analyses and found that schemes implemented after revision of the EU's agri-environmental programs in 2007 were not more effective than schemes implemented before revision. Furthermore, schemes aimed at areas out of production (such as field margins and hedgerows) are more effective at enhancing species richness than those aimed at productive areas (such as arable crops or grasslands). Outstanding research questions include whether AES enhance ecosystem services, whether they are more effective in agriculturally marginal areas than in intensively farmed areas, whether they are more or less cost-effective for farmland biodiversity than protected areas, and how much their effectiveness is influenced by farmer training and advice? The general lesson from the European experience is that AES can be effective for conserving wildlife on farmland, but they are expensive and need to be carefully designed and targeted. El Papel de los Esquemas Agro-Ambientales en la Conservación y el Manejo Ambiental Batáry et al. Resumen Más de la mitad de las tierras europeas está bajo manejo agrícola y así ha sido durante milenios. Muchas especies y ecosistemas de interés de conservación en Europa dependen del manejo agrícola y están mostrando una declinación continua. Los esquemas agro-ambientales (EAA) están diseñados en parte para encarar esto. Los esquemas son una gran fuente de financiamiento para la conservación dentro de la Unión Europea (UE) y el mayor gasto de conservación en Europa. Revisamos la estructura de los EAA actuales a lo largo del continente. Desde que en 2003 una revisión cuestionó la efectividad general de los EAA para la biodiversidad, ha habido una plétora de estudios de caso y meta-análisis que examinan su efectividad. La mayoría de las síntesis demuestran un incremento general en la biodiversidad de las tierras de cultivo en respuesta a los EAA, con la magnitud del efecto dependiente de la estructura y el manejo del terreno circundante. Esto es importante a la luz del crecimiento sucesivo de la UE y las continuas reformas a los EAA. Examinamos el cambio en la magnitud del efecto a través del tiempo al fusionar los conjuntos de datos de tres meta-análisis recientes y encontramos que los esquemas implementados después de la revisión de los programas agro-ambientales de la UE en 2007 no fueron más efectivos que los esquemas implementados antes de la revisión. Además, los esquemas enfocados en las áreas fuera de producción (como los márgenes de campo y los setos vivos) son más efectivos en el mejoramiento de la riqueza de especies que aquellos enfocados en las áreas productivas (como los cultivos arables y los pastizales). Las preguntas sobresalientes de la investigación incluyen si los EAA mejoran los servicios ambientales, si son más efectivos en las áreas agrícolas marginales que en las áreas de cultivo intensivo, si son más o menos rentables para la biodiversidad de las tierras de cultivo que las áreas protegidas, y en cuánto influye sobre su efectividad los consejos y el entrenamiento dado a los granjeros. La lección general de la experiencia europea es que los EAA pueden ser efectivos para la conservación de la vida silvestre en las tierras de cultivo, pero son caros y necesitan ser diseñados y enfocados cuidadosamente. PMID:25997591

Rare Compound Heterozygous Frameshift Mutations in ALMS1 Gene Identified Through Exome Sequencing in a Taiwanese Patient With Alström Syndrome.

PubMed

Tsai, Meng-Che; Yu, Hui-Wen; Liu, Tsunglin; Chou, Yen-Yin; Chiou, Yuan-Yow; Chen, Peng-Chieh

2018-01-01

Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p.Lys3431Serfs * 10) and a rare mutation in 16 (c.10823_10824delAG, p.Arg3609Alafs * 6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.

Effects of knowledge of an endangered species on recreationists' attitudes and stated behaviors and the significance of management compliance for ohlone tiger beetle conservation.

PubMed

Cornelisse, Tara M; Duane, Timothy P

2013-12-01

Recreation is a leading cause of species decline on public lands, yet sometimes it can be used as a tool for conservation. Engagement in recreational activities, such as hiking and biking, in endangered species habitats may even enhance public support for conservation efforts. We used the case of the endangered Ohlone tiger beetle (Cicindela ohlone) to investigate the effect of biking and hiking on the beetle's behavior and the role of recreationists' knowledge of and attitudes toward Ohlone tiger beetle in conservation of the species. In Inclusion Area A on the University of California Santa Cruz (U.S.A.) campus, adult Ohlone tiger beetles mate and forage in areas with bare ground, particularly on recreational trails; however, recreation disrupts these activities. We tested the effect of recreation on Ohlone tiger beetles by observing beetle behavior on trails as people walked and road bikes at slow and fast speed and on trails with no recreation. We also surveyed recreationists to investigate how their knowledge of the beetle affected their attitudes toward conservation of the beetle and stated compliance with regulations aimed at beetle conservation. Fast cycling caused the beetles to fly off the trail more often and to fly farther than slow cycling or hiking. Slow cycling and hiking did not differ in their effect on the number of times and distance the beetles flew off the trail. Recreationists' knowledge of the beetle led to increased stated compliance with regulations, and this stated compliance is likely to have tangible conservation outcomes for the beetle. Our results suggest management and education can mitigate the negative effect of recreation and promote conservation of endangered species. Efectos del Conocimiento de una Especie en Peligro sobre las Actitudes y Comportamientos Declarados de los Recreacionistas y el Significado del Manejo de la Conformidad para la Conservación del Escarabajo Tigre de Ohlone. © 2013 Society for Conservation Biology.

RASTREO DEL CANCER COLORRECTAL CONOCIMIENTO Y ACTITUD DE LA POBLACION

PubMed Central

CASAL, ENRIQUE R.; VELAZQUEZ, ELIZABETH N.; MEJIA, RAUL M.; CUNEO, ALDO; PEREZ-STABLE, ELISEO J.

2014-01-01

Resumen El rastreo de cáncer colorrectal (CCR) cuenta con fuertes evidencias en su favor. Datos preliminares indican que a pesar de ello no se lleva a cabo con la frecuencia adecuada. Se intenta aquí determinar, dentro de un Sistema de Salud que cuenta con los recursos necesarios, los elementos que facilitan o generan barreras para concretar esta práctica preventiva, cuántos individuos lo ponen en práctica y qué predice esta conducta. Se realizó una encuesta telefónica a los afiliados de una Obra Social de empleados de la Universidad de Buenos Aires, de los que 132 completaron el cuestionario (tasa de respuesta 70%). Los elementos considerados facilitadores del rastreo obtuvieron respuestas afirmativas en el 64 a 97%, mientras que los que definían barreras un 11 a 27%. En este último grupo, una categoría diferenciada la constituía el miedo a los efectos adversos: 39%, y el sentimiento de vergüenza relacionado con los procedimientos: 30%. Un 33% de los encuestados tenían hecho un método de rastreo, mayoritariamente de sangre oculta (27), sigmoideoscopía (11) y colonoscopía (20). Una mayoría afirmó que “se haría el procedimiento si el médico se lo recomendara” (95%), o “no se lo haría excepto que su médico se lo aconseje” (87%). Contestar afirmativamente que “los médicos hacen lo mejor para los pacientes” se asoció con haberse hecho un método de rastreo de CCR, OR 1.55 (IC 95%: 1.02-2.37) p: 0.04. El grupo de individuos estudiado parece bien predispuesto para el rastreo del CCR, la recomendación médica sería aquí un determinante prominente para ponerlo en práctica. PMID:19414294

Soil management effect on soil quality indicators in vineyards of the Appellation of Origin "Montilla-Moriles" in southern Spain

NASA Astrophysics Data System (ADS)

Guzmán, Gema; Cabezas, José Manuel; Bauer, Thomas; Strauss, Peter; Winter, Silvia; Zaller, Johann; Gómez, José Alfonso

2017-04-01

The effect soil management on several indicators frequently used in the assessment of soil quality it is not always reflected unambiguously when measured at the field although it is normally assumed that this relation is straightforward. Within the European project VineDivers (www.vinedivers.eu), sixteen commercial vineyards belonging to the Appellation of Origin "Montilla-Moriles" (Córdoba) and covering a wide range of textural classes were selected. These farms were classified 'a priori' under two soil management categories: temporal cover crop and bare soil during the whole year. In each of the vineyards one representative inter-row was selected in order to characterise different physical, chemical and biological parameters to evaluate some aspects related to soil quality. Results indicate that the studied indicators respond clearly to soil textural class and vegetation cover biomass. However, there was no clear difference in above-ground biomass of the two management categories (Guzmán et al., 2016). These results suggest that the interpretation and extrapolation of the indicators evaluated should incorporate complementary information to characterise small variations of soil management intensity among vineyards that are apparently managed under the same management category. The communication presents this analysis based on the number and type of soil disturbance events of all vineyards. The high variability found among vineyards under the same management highlights the relevance of measuring these soil parameters used as quality indicators, instead of extrapolating from other vineyards or agricultural systems, and interpreting them according to baseline levels. References: Guzmán G., Cabezas J.M., Gómez J.A. 2016. Evaluación preliminar del efecto del manejo del suelo en indicadores que determinan su calidad en viñedos de la Denominación de Origen Montilla Moriles. II Jornadas de Viticultura SECH. Madrid.

The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies.

PubMed

Diana, Anna; Polizzi, Angela Maria; Santostasi, Teresa; Ratclif, Luigi; Pantaleo, Maria Giuseppina; Leonetti, Giuseppina; Iusco, Danila Rosa; Gallo, Crescenzio; Conese, Massimo; Manca, Antonio

2016-06-01

Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis.

Thermogravimetric Control of Intermediate Products in the Metallurgy of Uranium; CONTROL TERMOGRAVIMETRICO DE PRODUCTOS INTERMEDIOS DE LA METALURGIA DEL URANIO

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

Sanchez, L.G.; Cellini, R.F.

1959-01-01

The thermal decomposition of some intermediate compounds in the metallurgy of uranium such as uranium peroxide, ammonium uranate, ammonium uranium pentafluoride, uranium tetrafluoride, and UO/sub 2/, were studied using Chevenard's thermobalance. Some data on the pyrolysis of synthetic mixtures of intermediate compounds which may appear during the industrial processing are given. Thermogravimetric methods of control are suggested for use in uranium metallurgy. (tr-auth)

[Infantile hypophosphatasia caused by a novel compound heterozygous mutation: a case report and pedigree analysis].

PubMed

Li, Deng-Feng; Lan, Dan; Zhong, Jing-Zi; Dewan, Roma Kajal; Xie, Yan-Shu; Yang, Ying

2017-05-01

This article reported the clinical features of one child with infantile hypophosphatasia (HPP) and his pedigree information. The proband was a 5-month-old boy with multiple skeletal dysplasia (koilosternia, bending deformity of both radii, and knock-knee deformity of both knees), feeding difficulty, reduction in body weight, developmental delay, recurrent pneumonia and respiratory failure, and a significant reduction in blood alkaline phosphatase. Among his parents, sister, uncle, and aunt (other family members did not cooperate with us in the examination), his parents and aunt had a slight reduction in alkaline phosphatase and his aunt had scoliosis; there were no other clinical phenotypes or abnormal laboratory testing results. His ALPL gene mutation came from c.228delG mutation in his mother and c.407G>A compound heterozygous mutation in his father. His aunt carried c.228delG mutation. The c.407G>A mutation had been reported as the pathogenic mutation of HPP, and c.228delG mutation was a novel pathogenic mutation. Hypophosphatasia is caused by ALPL gene mutation, and ALPL gene detection is an effective diagnostic method. This study expands the mutation spectrum of ALPL gene and provides a theoretical basis for genetic diagnosis of this disease.

Μicro-Raman spectroscopy for the characterization of rock-art pigments from Abrigo del Águila (Badajoz - Spain)

NASA Astrophysics Data System (ADS)

Rosina, P.; Gomes, H.; Collado, H.; Nicoli, M.; Volpe, L.; Vaccaro, C.

2018-06-01

Micro-Raman spectroscopic technique allowed the characterization of organic and inorganic pigments of different colours sampled from a rock-art shelter named Abrigo del Aguila, located in the district of Badajoz, Cabeza del Buey (Extremadura - Spain). Micro-Raman analyses has been coupled with SEM observation and elemental analyses (EDS). The white and the black colours, used for non-representative figures, have been identified respectively as anatase and amorphous carbon, while two different type of red pigment has been found on figurative representations. The darker one, sampled, from a sun-figure, comprises an indeterminate organic compound beside of hematite. The second one, sampled from an anthropomorphic figure, is of a brilliant red and only hematite has been recognized in it.

PubMed

Ávila García, Manuel; Huertas Delgado, Francisco Javier Huertas Delgado; Tercedor Sánchez, Pablo

2016-11-29

Introducción: España es el tercer país europeo con mayor prevalencia de obesidad infantil, dando lugar a la aparición de programas de intervención destinados a fomentar hábitos alimentarios saludables y/o de actividad física (AF).Objetivo: el propósito de esta revisión sistemática fue conocer aquellos programas de intervención para la promoción de hábitos alimentarios y de AF desarrollados en escolares españoles de Educación Primaria (EP) y analizar la influencia que han tenido las intervenciones sobre la composición corporal, los hábitos alimentarios y la AF.Método: se revisaron los artículos publicados entre los años 2000 y 2015 en las siguientes bases de datos: Web of Science, Scopus, Dialnet, PubMed, Eric, Sportdiscus y Psycinfo por dos revisores independientes.Resultados: se contabilizaron un total de 813 artículos, de los cuales tras la eliminación de duplicados (192), lectura de títulos y resumen (587) y lectura del texto completo (17), tan solo 7 cumplieron con los criterios de inclusión.Conclusiones: los programas de intervención analizados mostraron cambios positivos en la mejora de la composición corporal en algo menos de la mitad de los estudios analizados; por otro lado, casi todos los programas de intervención analizados tuvieron un efecto positivo sobre conductas respecto a ciertos hábitos alimentarios, como la ingesta de frutas, y sobre el incremento del nivel de AF.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation.

PubMed

Magdalena, N; Pilonetto, D V; Bitencourt, M A; Pereira, N F; Ribeiro, R C; Jeng, M; Pasquini, R

2005-05-01

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

Inverse modeling of groundwater flow in the semiarid evaporitic closed basin of Los Monegros, Spain

NASA Astrophysics Data System (ADS)

Samper-Calvete, F. J.; García-Vera, M. A.

Only minor attention has been given in the past to the study of closed-basin hydrogeology in evaporitic environments, because these basins usually contain poor-quality groundwater. The motivation for hydrogeological research in the Los Monegros area in northeastern Spain was the approval in 1986 of a large irrigation project in the Ebre River basin. The irrigation of 60,000 ha is planned, partly in an evaporitic closed basin containing playa lakes. The project has given rise to environmental concerns. The evaluation of the hydrologic impacts of irrigation requires quantifying properly the hydrogeology of the area. With the available information, a conceptual hydrogeological model was formulated that identifies two main aquifers connected through a leaky aquitard. On the basis of the conceptual model, a numerical model was calibrated under steady-state conditions using the method of maximum-likelihood automatic parameter estimation (Carrera and Neuman, 1986a). The calibrated model reproduces the measured hydraulic heads fairly well and is consistent with independent information on groundwater discharge. By the solution of the inverse problem, reliable parameter estimates were obtained. It is concluded that anisotropy plays a major role in some parts of the lower aquifer. The geometric average of model conductivity is almost two orders of magnitude larger than the average conductivity derived from small-scale field tests. This scale effect in hydraulic conductivity is consistent with the findings of Neuman (1994) and Sánchez-Vila et al. (1996). Résumé Dans le passé, on s'est peu intéresséà l'hydrogéologie des bassins fermés en milieu évaporitique, parce que ces bassins possèdent en général de l'eau souterraine de qualité médiocre. L'intérêt porté aux recherches hydrogéologiques dans la région de Los Monegros, dans le nord-est de l'Espagne est dûà l'approbation en 1986 d'un vaste projet d'irrigation dans le bassin de l'Ebre. L'irrigation de 60000 ha a été programmée, en partie dans un bassin évaporitique fermé où existent des lacs de playa. Le projet a fait émergé des préoccupations environnementales. L'évaluation des impacts hydrologiques de l'irrigation implique de quantifier correctement l'hydrogéologie de cette région. A partir des informations disponibles, un modèle hydrogéologique conceptuel a étéétabli il identifie deux aquifères principaux interconnectés par drainance au travers d'un imperméable. Un modèle numérique, établi sur la base de ce modèle conceptuel, a été calibré en conditions de régime permanent, en utilisant la méthode d'estimation automatique du maximum de vraisemblance des paramètres (Carrera and Neuman, 1986a). Le modèle calibré reproduit correctement la piézométrie mesurée et est en accord avec les informations concernant l'écoulement des nappes. La résolution du problème inverse a fourni des estimations acceptables des paramètres. On en a conclu que l'anisotropie joue un rôle essentiel dans certaines parties de l'aquifère inférieur. La moyenne géométrique de la conductivité hydraulique est d'environ deux ordres de grandeur plus élevée que la conductivité hydraulique moyenne obtenue par des essais de terrain à l'échelle locale. Cet effet d'échelle sur la conductivité hydraulique est conforme aux résultats obtenus par Neuman (1994) et Sánchez-Vila et al. (1996). Resumen La hidrogeología de zonas endorreicas en zonas evaporíticas ha recibido muy poca atención en el pasado debido fundamentalmente a que en estas zonas las aguas subterráneas tienen una elevada salinidad debido a la alta solubilidad de sus materiales. El interés por la hidrogeología de la zona de Los Monegros en el noreste de España surgió a raiz de la aprobación en 1986 del proyecto de Los Monegros II en la zona central del valle del Ebro que contempla la puesta en regadío de 60,000 ha, algunas de las cuales se encuentran situadas en la zona endorreica de Los Monegros en la que existen toda una serie de lagunas salinas. La implantación del regadío en esta zona puede alterar el régimen hidrológico de las lagunas, provocar problemas de salinización de suelos y aguas y aumentar la salinidad del río Ebro. Con el fin de evaluar estos efectos se construyó un modelo numérico del flujo subterráneo. Con la información disponible se pueden distinguir dos acuíferos que están conectados mediante un acuitardo. El modelo de flujo se calibró en régimen estacionario utilizando el procedimiento de calibración automática de Carrera y Neuman (1986a) basado en el método de la máxima verosimilitud. El modelo finalmente calibrado es capaz de reproducir los niveles piezométricos medidos y es coherente con los resultados de los balances hidrológicos en las lagunas. La conductividad hidráulica media del modelo es superior en casi dos órdenes de magnitud a la media de las conductividades hidráulicas obtenidas en ensayos de campo a escala local. Este efecto de escala en la conductividad hidráulica es coherente con los resultados de Neuman (1994) y Sánchez-Vila et al. (1996) y confirma que dicho efecto también se observa en medios evaporíticos.

Molecular defects leading to human complement component C6 deficiency in an African-American family

PubMed Central

Zhu, Z-B; Totemchokchyakarn, K; Atkinson, T P; Volanakis, J E

1998-01-01

Complement component C6 deficiency (C6D) was diagnosed in a 16-year-old African-American male with meningococcal meningitis. The patient's father and two brothers also had C6D, but gave no history of meningitis or other neisserial infection. By using exon-specific polymerase chain reaction (PCR)/single-strand conformation polymorphism as a screening step and nucleotide sequencing of target exons, we determined that the proband was a compound heterozygote for two C6 gene mutations. The first, 1195delC located in exon 7, is a novel mutation, while the second, 1936delG in exon 12, has been described before to cause C6D in an unrelated African-American individual. Both mutations result in premature termination codons and C6 null alleles. Allele-specific PCR indicated that the proband's two brothers also inherited the 1195delC mutation from their heterozygous mother and the 1936delG mutation from their homozygous father. PMID:9472666

Matrine in association with FD-2 stimulates F508del-cystic fibrosis transmembrane conductance regulator activity in the presence of corrector VX809

PubMed Central

Marengo, Barbara; Speciale, Andrea; Senatore, Lisa; Garibaldi, Silvano; Musumeci, Francesca; Nieddu, Erika; Pollarolo, Benedetta; Pronzato, Maria Adelaide; Schenone, Silvia; Mazzei, Mauro; Domenicotti, Cinzia

2017-01-01

Cystic fibrosis is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the predominant mutation is termed Phe508del (F508del). Therapy for F508del-CFTR patients is based on the use of Orkambi®, a combination of VX809 and VX770. However, though Orkambi leads to an improvement in the lung function of patients, a progressive reduction in its efficacy has been observed. In order to overcome this effect, the aim of the present study was to investigate the role of matrine and the in-house compound FD-2 in increasing the action of VX809 and VX770. Fischer rat thyroid cells overexpressing F508del-CFTR were treated with matrine, VX809 (corrector) and/or with a number of potentiators (VX770, FD-1 and FD-2). The results demonstrated that matrine was able to stimulate CFTR activity and, in association with FD-2, increased the functionality of the channel in the presence of VX809. Based on these results, it may be hypothesized that FD-2 may be a novel and more effective potentiator compared with VX770. PMID:29039559

Two Small Molecules Restore Stability to a Subpopulation of the Cystic Fibrosis Transmembrane Conductance Regulator with the Predominant Disease-causing Mutation.

PubMed

Meng, Xin; Wang, Yiting; Wang, Xiaomeng; Wrennall, Joe A; Rimington, Tracy L; Li, Hongyu; Cai, Zhiwei; Ford, Robert C; Sheppard, David N

2017-03-03

Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl - channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopic CFTR Cl - currents. At 37 °C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wild-type CFTR, the full-length F508del-CFTR was about 10 °C less thermostable. Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl - channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl - currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl - channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease].

PubMed

Bao, Y M; Liu, X L; Liu, X L; Chen, J H; Zheng, Y J

2017-11-02

Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed). Result: The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography (HRCT) revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation (c.1755delC+c.2890G>A) in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion: c.1755delC+c.2890G>A is a new kind of compound heterozygous mutation in ABCA3, which can cause children's diffuse parenchymal lung disease. Its phenotype is related to its genotype.

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

Meats, A.

Both wild and released (sterile) Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) and wild Bactrocera papayae (Drew and Hancock) in Australia had patchy distributions and comparisons with predictions of the negative binomial model indicated that the degree of clumping was sometimes very high, particularly at low densities during eradication. An increase of mean recapture rate of sterile B. tryoni on either of 2 trap arrays was not accompanied by a reduction in its coefficient of variation and when recapture rates were high, the percentage of traps catching zero decreased only slightly with increase in recapture rate, indicating that it is not practicablemore » to decrease the heterogeneity of dispersion of sterile flies by increasing the number released. There was often a mismatch between the dispersion patterns of the wild and sterile flies, and the implications of this for the efficiency of the sterile insect technique (SIT) were investigated with a simulation study with the observed degrees of mismatch obtained from the monitoring data and assuming the overall ratio of sterile to wild flies to be 100:1. The simulation indicated that mismatches could result in the imposed rate of increase of wild flies being up to 3.5 times higher than that intended (i.e., 0.35 instead of 0.1). The effect of a mismatch always reduces the efficiency of SIT. The reason for this asymmetry is discussed and a comparison made with host-parasitoid and other systems. A release strategy to counter this effect is suggested. (author) [Spanish] Las moscas naturales y liberadas (esteriles) de Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) y Bactrocera papayae (Drew and Hancock) en Australia tuvieron distribuciones en parches y sus compariciones con las predicciones de un modelo binomial negativo indicaron un nivel de agregacion a veces fue muy alto, particularmente en las densidades bajas durante de eradicacion. Un aumento en el promedio de la tasa de B. tryoni esteriles recapturadas en las dos formas de trampas no fue acompanado por una reduccion en su coeficiente de variacion y cuando las tasas de moscas recapturadas fue alto, el porcentaje de las trampas que capturaron ninguna mosca bajo solo un poco con un aumento en la tasa de las moscas recapturadas, esto indico que no es practicable bajar la heterogenicidad de dispersion de las moscas esteriles por medio de un aumento el numero de moscas liberadas. Muy a menudo se encontro un desajusto entre los patrones de dispersion de las moscas naturales y esteriles, y las implicaciones de esto para la eficiencia de la tecnica del insecto esteril (TIE) fueron investigadas en un estudio de simulacion con los grados de desajustes observados obtenidos de los datos del monitoreo y se considero que la razon general del numero de moscas esteriles a moscas naturales fueron 100:1. La simulacion indico que los desajustes en los patrones de dispersion pueden resultar en una tasa impuesta sobre el aumento de las moscas naturales de hasta 3.5 veces mas alta que la tasa intentada (i.e., 0.35 en vez de 0.1). El efecto de un desajuste siempre reduce la eficiencia de TIS. Se discute la razon para esta asimetria y una comparicion hecha con el sistema de hospedero-parasitoid y otros sistemas. Se sugiere una estrategia de liberacion para contrarrestar este efecto. (author)« less

Measurement of Family-centered care perception and parental stress in a neonatal unit.

PubMed

Balbino, Flávia Simphronio; Balieiro, Maria Magda Ferreira Gomes; Mandetta, Myriam Aparecida

2016-08-08

to evaluate the effects of the implementation of the Patient and Family-Centered Care Model on parents and healthcare perceptions and parental stress. a quasi-experimental study developed in a neonatal unit of a university hospital in the municipality of São Paulo, Brazil, with the implementation of this model of care. Data collection were performed by two sample groups, one using non-equivalent groups of parents, and another using equivalent groups of healthcare professionals. The instruments Perceptions of Family-Centered Care-Parent Brazilian Version, Perceptions of Family-Centered Care-Staff Brazilian Version and Parental Stress Scale: Neonatal Intensive Care Unit, were applied to 132 parents of newborns hospitalized and to 57 professionals. there was a statistically significant improvement in the perceptions of the parents in most items assessed (p ≤0,05) and for the staff in relation to the family welcome in the neonatal unit (p = 0.041) and to the comprehension of the family's experience with the infant´s hospitalization (p = 0,050). There was a reduction in the average scores of parental stress, with a greater decrease in the Alteration in Parental Role from 4,2 to 3,8 (p = 0,048). the interventions improved the perceptions of parents and healthcare team related to patient and family-centered care and contributed to reducing parental stress. avaliar os efeitos da implementação do Modelo do Cuidado Centrado no Paciente e Família na percepção de pais e profissionais de saúde e no estresse parental. Estudo quase experimental com grupos não equivalentes para avaliação dos efeitos da intervenção na percepção de pais; e com grupos equivalentes para a avaliação na percepção de profissionais de saúde, desenvolvido na unidade neonatal de um hospital universitário do município de São Paulo. Os instrumentos, Percepção do Cuidado Centrado na Família- Pais versão brasileira, Percepção do Cuidado Centrado na Família- Equipe versão brasileira e Parental Stress Scale: Neonatal Intensive Care Unit, foram aplicados com 132 pais de recém-nascidos internados e 57 profissionais da equipe. houve melhora estatisticamente significante na percepção dos pais na maioria dos itens avaliados (p≤0,05) e para os profissionais em relação ao acolhimento da família na unidade neonatal (p= 0,041) e a compreensão da vivência da família com a hospitalização (p=0,050). Houve redução dos escores médios do estresse parental, com maior queda na Alteração do Papel de Pais de 4,2 para 3,8 (p=0,048). as intervenções realizadas melhoraram a percepção de pais e de profissionais da equipe de saúde sobre o Cuidado Centrado no Paciente e Família e contribuíram para a redução do estresse parental. evaluar los efectos de la implementación del Modelo del Cuidado Centrado en el Paciente y la Familia en la percepción de los padres y profesionales de la salud y en lo estrés parental. estudio cuasi-experimental con grupos no equivalentes para evaluar los efectos de la intervención en la percepción de los padres; y grupos equivalentes para evaluar la percepción de los profesionales de la salud, desarrollado en la unidad neonatal de un hospital universitario en el municipio de Sao Paulo. Los instrumentos de Percepción del Cuidado Centrado en el Paciente y la Familia- Padres versión brasileña, Percepción del Cuidado Centrado en el Paciente y la Familia-Equipo versión brasileña y Parental Stress Scale: Neonatal Intensive Care Unit, se aplicaron a 132 padres de los recién nacidos hospitalizados y 57 profesional del equipo. se observó una mejoría estadísticamente significativa en la percepción de los padres en la mayoría de los ítems evaluados (p = 0,05) y para los profesionales en relación con el cuidado de la familia en la unidad neonatal (p = 0,041) y la comprensión de la experiencia de la familia con la hospitalización (p = 0,050). Hubo una reducción en las puntuaciones medias de estrés de los padres, con una mayor disminución en la Alteración del Rol Parental 4.2 a 3.8 (p = 0,048). las intervenciones mejoran la percepción de los padres y los profesionales del equipo de salud en el Cuidado Centrado en el Paciente y la Familia y ha contribuido a reducir el estrés de los padres.

Aquifer overexploitation: what does it mean?

NASA Astrophysics Data System (ADS)

Custodio, Emilio

2002-02-01

Groundwater overexploitation and aquifer overexploitation are terms that are becoming common in water-resources management. Hydrologists, managers and journalists use them when talking about stressed aquifers or some groundwater conflict. Overexploitation may be defined as the situation in which, for some years, average aquifer ion rate is greater than, or close to the average recharge rate. But rate and extent of recharge areas are often very uncertain. Besides, they may be modified by human activities and aquifer development. In practice, however, an aquifer is often considered as overexploited when some persistent negative results of aquifer development are felt or perceived, such as a continuous water-level drawdown, progressive water-quality deterioration, increase of ion cost, or ecological damage. But negative results do not necessarily imply that ion is greater than recharge. They may be simply due to well interferences and the long transient period that follow changes in the aquifer water balance. Groundwater storage is depleted to some extent during the transient period after ion is increased. Its duration depends on aquifer size, specific storage and permeability. Which level of "aquifer overexploitation" is advisable or bearable, depends on the detailed and updated consideration of aquifer-development effects and the measures implemented for correction. This should not be the result of applying general rules based on some indirect data. Monitoring, sound aquifer knowledge, and calculation or modelling of behaviour are needed in the framework of a set of objectives and policies. They should be established by a management institution, with the involvement of groundwater stakeholders, and take into account the environmental and social constraints. Aquifer overexploitation, which often is perceived to be associated with something ethically bad, is not necessarily detrimental if it is not permanent. It may be a step towards sustainable development. Actually, the term aquifer overexploitation is mostly a qualifier that intends to point to a concern about the evolution of the aquifer-flow system in some specific, restricted points of view, but without a precise hydrodynamic meaning. Implementing groundwater management and protection measures needs quantitative appraisal of aquifer evolution and effects based on detailed multidisciplinary studies, which have to be supported by reliable data. Resumé. La surexploitation de l'eau souterraine et la surexploitation des nappes sont des termes qui deviennent d'usage commun en gestion de l'eau. Plusieurs hydrologues, aménageurs et journalistes en font usage quand on parle d'une nappe exploitée intensivement et qui présente des situations conflictives. On peut définir la surexploitation comme étant la situation dans laquelle l'extraction moyenne d'eau souterraine est plus grande ou proche de la recharge moyenne pendant quelques années. Mais le taux ansi que la surface de cette recharge sont souvent tres incertains et peuvent changer dûs a des activitées humaines et à l'exploitation de la nappe elle-méme. Du point de vue pratique on souvent considère qu'il y a surexploitation quand on observe or on s'aperçoit de certains résultats négatifs de l'exploitation, tels qu'une diminution continue du niveau de l'eau, une detérioration de sa qualité, une augmentation du coût d' extraction, ou dommages écologiques. Mais ces effets négatifs n' impliquent pas nécessairement que l'extraction soit plus grande que la recharge. Ils peuvent étre simplement le résultat d'interférences ou d'une longue période transitoire qui suivent les changements dans les termes du bilan hydrique. Cette période transitoire a une durée que dépend de la taille de la nappe, et de son coefficient d' emmagasinement et de sa perméabilité. Les extractions d'eau de la nappe comportent une diminution de l'emmagasinement d'eau souterraine pendant le période transitoire. A fin de pouvoir décider du degré de "surexploitation de la nappe" conseillé ou admisible on a besoin de la description detaillée et à jour des effets de l'exploitation et des mesures de correction adoptées. Cette décision ne peut pas étre prise uniquement à partir de regles générales et l'appui de quelques observations indirectes. On a besoin de controle, d'une bonne connaissance de la nappe, et de calculer ou modeliser le comportement, en faisant appel à l'ensemble des objectifs et politiques établies par une institution de gestion, avec l'implication des personnes qui sont intéressées par l'eau souterraine, et tenant compte des conditions environmentales et sociales. La surexploitation de nappes, qui souvent est associée a quelque chose éthiquement nocive, n'est pas necessairement ainsi pendant un certain temps, et peut être une étape dans l'évolution vers un développement durable. Réellement la designation de surexploitation de nappes est surtout un adjectif que a pour but de qualifier une évolution préoccupante sous certains points de vue, mais sans une signification hydrodynamique précise. Pour adopter des mesures de gestion et protection, on a besoin de l'évaluation quantitative de l'évolution de la nappe et de ses effets, ce qui doit déboucher sur des études detaillées dans un contexte multidisciplinaire, et sur de bonnes données. Resumen. La sobreexpolotación del agua subterránea y la sobreexplotacion de acuíferos son conceptos que se están convirtiendo en términos de uso común en gestión hídrica. Muchos hidrólogos, gestores y periodistas las usan para referirse a un acuífero explotado intensamente o que presenta situaciones conflictivas. La sobreexplotación se puede definir como la situación en la que durante varios años la extracción media de agua subterránea de un acuífero supera o se aproxima a la recarga media. Pero la tasa y también la superficie sobre la que se realiza esta recarga son a menudo muy inciertas, y pueden cambiar por actividades humanas y por la propia explotación del acuífero. Sin embargo, en la práctica se suele considerar que hay sobreexplotación cuando se observan o se perciben ciertos resultados negativos de la explotación, tales como un descenso continuado del nivel del agua, un deterioro de su calidad, un encarecimiento del agua extraída, o daños ecológicos. Pero estos efectos no están necesariamente relacionados con el hecho de que la extracción sea mayor que la recarga, puesto que pueden ser simplemente el resultado de interferencias o del dilatado período transitorio que sigue a los cambios en los términos del balance de agua, y cuya duración depende del tamaño del acuífero, y de su permeabilidad y coeficiente de almacenamiento. Las extracciones del acuífero suponen una disminución del almacenamiento de agua subterránea durante este periodo transitorio. Para decidir que grado de "sobreexplotación del acuífero" es aconsejable o admisible hace falta la consideración detallada y actualizada de los efectos de la explotación y las medidas de corrección que se adopten. Para esa decisión no basta con reglas generales y el apoyo de algunas observaciones indirectas. Se necesitan observaciones de control, buen conocimiento del acuífero y cálculos o modelación del comportamiento, y todo ello en el marco de un conjunto de objetivos y políticas establecidas por una institución de gestión, con la implicación de aquellos que tienen un interés en el agua subterránea, y teniendo en cuenta los condicionantes ambientales y sociales. La sobreexplotación de acuíferos, que con frecuencia suele asociarse a algo éticamente malo, no tiene por qué ser necesariamente así durante cierto tiempo, sino una etapa en la evolución hacia un desarrollo sustentable. En la realidad la designación de sobreexplotación de acuíferos es principalmente un adjetivo que trata de calificar a una evolución preocupante bajo determinados puntos de vista, sin que tenga una significación hidrodinámica precisa. Para adoptar medidas de gestión y de protección se necesita la evaluación cuantitativa de la evolución del acuífero y sus efectos, que se derivan de estudios de detalle en un contexto multidisciplinar y de datos fiables.

Primary microcephaly caused by novel compound heterozygous mutations in ASPM

PubMed Central

Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

2018-01-01

Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated (ASPM) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified. PMID:29644084

Primary microcephaly caused by novel compound heterozygous mutations in ASPM.

PubMed

Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

2018-01-01

Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated ( ASPM ) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified.

Genetic deletion of keratin 8 corrects the altered bone formation and osteopenia in a mouse model of cystic fibrosis.

PubMed

Le Henaff, Carole; Faria Da Cunha, Mélanie; Hatton, Aurélie; Tondelier, Danielle; Marty, Caroline; Collet, Corinne; Zarka, Mylène; Geoffroy, Valérie; Zatloukal, Kurt; Laplantine, Emmanuel; Edelman, Aleksander; Sermet-Gaudelus, Isabelle; Marie, Pierre J

2016-04-01

Patients with cystic fibrosis (CF) display low bone mass and alterations in bone formation. Mice carrying the F508del genetic mutation in the cystic fibrosis conductance regulator (Cftr) gene display reduced bone formation and decreased bone mass. However, the underlying molecular mechanisms leading to these skeletal defects are unknown, which precludes the development of an efficient anti-osteoporotic therapeutic strategy. Here we report a key role for the intermediate filament protein keratin 8 (Krt8), in the osteoblast dysfunctions in F508del-Cftr mice. We found that murine and human osteoblasts express Cftr and Krt8 at low levels. Genetic studies showed that Krt8 deletion (Krt8(-/-)) in F508del-Cftr mice increased the levels of circulating markers of bone formation, corrected the expression of osteoblast phenotypic genes, promoted trabecular bone formation and improved bone mass and microarchitecture. Mechanistically, Krt8 deletion in F508del-Cftr mice corrected overactive NF-κB signaling and decreased Wnt-β-catenin signaling induced by the F508del-Cftr mutation in osteoblasts. In vitro, treatment with compound 407, which specifically disrupts the Krt8-F508del-Cftr interaction in epithelial cells, corrected the abnormal NF-κB and Wnt-β-catenin signaling and the altered phenotypic gene expression in F508del-Cftr osteoblasts. In vivo, short-term treatment with 407 corrected the altered Wnt-β-catenin signaling and bone formation in F508del-Cftr mice. Collectively, the results show that genetic or pharmacologic targeting of Krt8 leads to correction of osteoblast dysfunctions, altered bone formation and osteopenia in F508del-Cftr mice, providing a therapeutic strategy targeting the Krt8-F508del-CFTR interaction to correct the abnormal bone formation and bone loss in cystic fibrosis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Not Available].

PubMed

San Mauro-Martín, Ismael; Collado-Yurrita, Luis; Blumenfeld-Olivares, Javier Andrés; Cuadrado-Cenzual, María Ángeles; Calle-Purón, María Elisa; Hernández-Cabria, Marta; Garicano-Vilar, Elena; Pérez-Arruche, Eva; Arce-Delgado, Esperanza; CiudadCabañas, María José

2016-06-30

Introducción: la hipercolesterolemia es uno de los principales factores de riesgo en la enfermedad cardiovascular. Los esteroles vegetales se han postulado como agentes reguladores y beneficiosos para el control de esta.Objetivo: analizar el efecto de los esteroles vegetales añadidos en una leche en la reducción del colesterol plasmático en adultos jóvenes.Métodos: ensayo clínico, controlado, aleatorizado, doble ciego y cruzado. Los esteroles (2,24 g diarios) fueron administrados en dos tomas de 350 ml de una leche comercial desnatada, durante dos periodos de 3 semanas, separados por una "fase de lavado" de 2 semanas, en el grupo experimental. Al grupo control se le administró la misma cantidad de leche desnatada, sin esteroles. Tanto al inicio como al final de cadaperiodo de intervención se extrajeron muestras sanguíneas. Se analizaron la composición corporal, hábitos de salud y los siguientes marcadores sanguíneos: perfil lipídico, hematológico, inflamación, etc.Resultados: se incluyeron 54 personas en el estudio con una edad media de 38,8 ± 7,3 años. La diferencia porcentual entre los marcadores basales y finales para el colesterol total, colesterol-LDL, colesterol-HDL, triglicéridos y colesterol no-HDL fueron del 9,73%, 12,5%, 1,9%, 3,15% y 13,2%, respectivamente. Se obtuvieron diferencias estadísticamente significativas entre el grupo experimental y el grupo control, para todos los marcadores analizados excepto para los triglicéridos.Conclusión: los esteroles vegetales suministrados en un alimento de consumo habitual, como la leche, pueden ser una estrategia terapéutica no farmacológica para el control de la hipercolesterolemia de alto interés sanitario.

Strange Stars, Neutron Stars and Pulsar Emission

NASA Astrophysics Data System (ADS)

Benvenuto, O. G.; Horvath, J. E.

1990-11-01

RESUMEN. Se ha conjeturado que una partlecula de dieciocho quarks, sin Carga, sin espi'n y sin colar (quark-alfa) podri'a ser estable a ba5as tern peraturas y presiones aiTh COfl respecto a materia extrafla. Presentamos en este trabajo la estmctura de estrellas extraflas incluyendo los efectos y apariencia de parti'culas uark-alfa en las capas exteriores. La estruc tura interna ya no es hoinogenea del centro a la superficie, sino que muestra un centro de materia extrafla, capas s6lidas y una costra delgada de materia normal en la superficie. La superficie de materia nonnal permite la fornaci6n de una magnetosfera, la que se piensa sea el sitlo en donde ocurre la emisi6n del pulsar. La superficie de superflui'do ayuda a explicar el fen6rneno de `glitch', el cual ba sido observado en muchos pulsares. Se discute la ecuaci6n de estado para rnateria quark-alfa relevante en este regimen. ABSTIZACT:It has been conjectured that an quark, uncharged, spinless and colorless particle Cquark-alpha) could be stable at low pressures and temperatures even with respect to strange matter. We present in work tlie structure of stars including the effects of the appearance of quark-alpi' particles ii their outer layers. The internal structure is no longer from tlie center to the surface, but show a strange matter core, a solid and superfluid layers and a thin crust of normal matter at the surface. The normal matter surface allows tlie fon tion of a magnetosphere, whicl is to be tl place where pulsar emission occurs. A superfluid layer helps to explain tlie glitch , wlflch has been observed in . equation of state for quark-alpha matter relevant in regime is also discussed. Keq LA)OtL : ARY S - OF STATF - ?.ACT

Rescue of murine F508del CFTR activity in native intestine by low temperature and proteasome inhibitors.

PubMed

Wilke, Martina; Bot, Alice; Jorna, Huub; Scholte, Bob J; de Jonge, Hugo R

2012-01-01

Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correctors) or at enhancing the open probability of the CFTR chloride channel (CFTR potentiators). Preventing premature breakdown of F508del CFTR is an alternative or additional strategy, which is investigated in this study. We established an ex vivo assay for murine F508del CFTR rescue in native intestinal epithelium that can be used as a pre-clinical test for candidate therapeutics. Overnight incubation of muscle stripped ileum in modified William's E medium at low temperature (26°C), and 4 h or 6 h incubation at 37°C with different proteasome inhibitors (PI: ALLN, MG-132, epoxomicin, PS341/bortezomib) resulted in fifty to hundred percent respectively of the wild type CFTR mediated chloride secretion (forskolin induced short-circuit current). The functional rescue was accompanied by enhanced expression of the murine F508del CFTR protein at the apical surface of intestinal crypts and a gain in the amount of complex-glycosylated CFTR (band C) up to 20% of WT levels. Sustained rescue in the presence of brefeldin A shows the involvement of a post-Golgi compartment in murine F508del CFTR degradation, as was shown earlier for its human counterpart. Our data show that proteasome inhibitors are promising candidate compounds for improving rescue of human F508del CFTR function, in combination with available correctors and potentiators.

Medición de los parámetros cosmológicos q0, ΩM, y ΩΛ, usando supernovas de Tipo Ia distantes

NASA Astrophysics Data System (ADS)

Clocchiatti, A.; High-Z Sne Search Team

Las supernovas de tipo Ia son una herramienta de gran precisión para la medición de distancias de interés cosmológico. Los métodos recientes de calibración de su luminosidad intrínseca, que hacen uso de la forma de las curvas de luz en varios colores y permiten diferenciar entre supernovas distantes, intrínsecamente débiles, u oscurecidas por extinción, reducen la dispersión del método que las asume de magnitud absoluta constante de 0.50 mag a 0.15 mag, e incrementa el valor de la constante de Hubble de ~55 km s-1 Mpc-1, a 65 km s-1 Mpc-1. A partir de la calibración de las supernovas cercanas, con redshifts menores que 0.1, se pueden obtener distancias precisas a supernovas que explotan a alto redshift. Hemos aplicado estos métodos a 16 supernovas con 0.16 < Z < 0.97, encontrando que sus distancias son, en promedio, entre 10% y 13% (dependiendo del método empleado) mayores que las que uno esperaría en un universo con poca masa (Ω = 0.2), sin una constante cosmológica. Todos los métodos de ajuste de curvas de luz, y selección de subgrupos de la muestra de supernovas observadas, favorecen consistentemente modelos del universo que se expanden eternamente y que tienen una constante cosmológica positiva (ΩΛ > 0), y una aceleración de la expansión al presente (q0 < 0). Hay distintas fuentes de posibles errores sistemáticos que merecen ser analizadas, entre ellas: evolución de la metalicidad y estrellas progenitoras, extinción, bias en la elección de la muestra, amplificación por gravitational lensing, y contaminación de la muestra. Ninguno de estos efectos alcanza para reconciliar los datos con ΩΛ = 0, o q0 > 0.

Transcriptomic profiling and quantitative high-throughput (qHTS) drug screening of CDH1 deficient hereditary diffuse gastric cancer (HDGC) cells identify treatment leads for familial gastric cancer.

PubMed

Chen, Ina; Mathews-Greiner, Lesley; Li, Dandan; Abisoye-Ogunniyan, Abisola; Ray, Satyajit; Bian, Yansong; Shukla, Vivek; Zhang, Xiaohu; Guha, Raj; Thomas, Craig; Gryder, Berkley; Zacharia, Athina; Beane, Joal D; Ravichandran, Sarangan; Ferrer, Marc; Rudloff, Udo

2017-05-01

Patients with hereditary diffuse gastric cancer (HDGC), a cancer predisposition syndrome associated with germline mutations of the CDH1 (E-cadherin) gene, have few effective treatment options. Despite marked differences in natural history, histopathology, and genetic profile to patients afflicted by sporadic gastric cancer, patients with HDGC receive, in large, identical systemic regimens. The lack of a robust preclinical in vitro system suitable for effective drug screening has been one of the obstacles to date which has hampered therapeutic advances in this rare disease. In order to identify therapeutic leads selective for the HDGC subtype of gastric cancer, we compared gene expression profiles and drug phenotype derived from an oncology library of 1912 compounds between gastric cancer cells established from a patient with metastatic HDGC harboring a c.1380delA CDH1 germline variant and sporadic gastric cancer cells. Unsupervised hierarchical cluster analysis shows select gene expression alterations in c.1380delA CDH1 SB.mhdgc-1 cells compared to a panel of sporadic gastric cancer cell lines with enrichment of ERK1-ERK2 (extracellular signal regulated kinase) and IP3 (inositol trisphosphate)/DAG (diacylglycerol) signaling as the top networks in c.1380delA SB.mhdgc-1 cells. Intracellular phosphatidylinositol intermediaries were increased upon direct measure in c.1380delA CDH1 SB.mhdgc-1 cells. Differential high-throughput drug screening of c.1380delA CDH1 SB.mhdgc-1 versus sporadic gastric cancer cells identified several compound classes with enriched activity in c.1380 CDH1 SB.mhdgc-1 cells including mTOR (Mammalian Target Of Rapamycin), MEK (Mitogen-Activated Protein Kinase), c-Src kinase, FAK (Focal Adhesion Kinase), PKC (Protein Kinase C), or TOPO2 (Topoisomerase II) inhibitors. Upon additional drug response testing, dual PI3K (Phosphatidylinositol 3-Kinase)/mTOR and topoisomerase 2A inhibitors displayed up to >100-fold increased activity in hereditary c.1380delA CDH1 gastric cancer cells inducing apoptosis most effectively in cells with deficient CDH1 function. Integrated pharmacological and transcriptomic profiling of hereditary diffuse gastric cancer cells with a loss-of-function c.1380delA CDH1 mutation implies various pharmacological vulnerabilities selective to CDH1-deficient familial gastric cancer cells and suggests novel treatment leads for future preclinical and clinical treatment studies of familial gastric cancer.

The Evolution of Population III Objects

NASA Astrophysics Data System (ADS)

de Araujo, J. C. N.; Opher, R.

1990-11-01

RESUMEN. Estudiamos el enfriamiento y colapso de las perturbaciones iso- termicas de masa M % Mj (masa de Jeans en la era de recombinaci6n) y M « Mj tomando en consideraci5n la expansi6n del Universo, presi6n, arrastre de fotones, enfriamiento de fotones (calentamiento), fotoioni- zaci6n, ionizaci5n por colisiones y la formaci6n y enfriamiento de mo- leculas de hidr6geno. Tambien estudiamos el efecto de no-esfericidad, rotaci6n y campos magneticos en el colapso de M % Mj debido a perturbaciones residuales que sobreviven para N « Mj. ABSTRACT. We study the cooling and collapse of isothermal perturbations of mass N % Nj (Jeans mass at recombination era) and N « NJ taking into account the expansion of the Universe, pressure, photon-drag, photon -cooling (heating), photoionization, collisional ionization and the formation and cooling of hydrogen molecules. We also study the effect of the nonsphericity, rotation and magnetic fields in the collapse of N % NJ. The formation of protostars from the fragmentation of clouds of mass M % MJ due to the residual perturbations that survive for N « NJ is also investigated. K ok : HYDRODYNANICS - STARS-POPULATION III

Novel compound heterozygous mutations in the GPR98 (USH2C) gene identified by whole exome sequencing in a Moroccan deaf family.

PubMed

Bousfiha, Amale; Bakhchane, Amina; Charoute, Hicham; Detsouli, Mustapha; Rouba, Hassan; Charif, Majida; Lenaers, Guy; Barakat, Abdelhamid

2017-10-01

In the present work, we identified two novel compound heterozygote mutations in the GPR98 (G protein-coupled receptor 98) gene causing Usher syndrome. Whole-exome sequencing was performed to study the genetic causes of Usher syndrome in a Moroccan family with three affected siblings. We identify two novel compound heterozygote mutations (c.1054C > A, c.16544delT) in the GPR98 gene in the three affected siblings carrying post-linguale bilateral moderate hearing loss with normal vestibular functions and before installing visual disturbances. This is the first time that mutations in the GPR98 gene are described in the Moroccan deaf patients.

Isospin influence on the decay modes of compound nuclei produced in the 78, 86Kr + 40, 48Ca at 10 MeV/nucleon

NASA Astrophysics Data System (ADS)

Pirrone, S.; Politi, G.; Wieleczko, J. P.; Gnoffo, B.; De Filippo, E.; La Commara, M.; Russotto, P.; Trimarchi, M.; Vigilante, M.; Ademard, G.; Auditore, L.; Beck, C.; Bercenau, I.; Bonnet, E.; Borderie, B.; Cardella, G.; Chibihi, A.; Colonna, M.; D'Onofrio, A.; Frankland, J. D.; Lanzalone, G.; Lautesse, P.; Lebhertz, D.; Le Neidre, N.; Lombardo, I.; Mazurek, K.; Pagano, A.; Pagano, E. V.; Papa, M.; Piasecki, E.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Spadaccini, G.; Trifirò, A.; Verde, G.

2017-09-01

The study of the decay modes competition of the compound systems produced in the collisions ^{78}{Kr} + ^{40}{Ca} and ^{86}{Kr} + ^{48}{Ca} at 10MeV/A is presented. In particular, the N / Z entrance channel influence on the decay paths of the compound systems, directly connected to the isospin influence, is investigated. The experiment was performed at the INFN Laboratori Nazionali del Sud (LNS) in Catania by using the 4 π multi-detector CHIMERA. Charge, mass, angular distributions and kinematical features of the reaction products were studied. The analysis shows some differences in the contribution arising from the various reaction mechanisms for the neutron-poor and neutron-rich systems.

Mapping of Drug-like Chemical Universe with Reduced Complexity Molecular Frameworks.

PubMed

Kontijevskis, Aleksejs

2017-04-24

The emergence of the DNA-encoded chemical libraries (DEL) field in the past decade has attracted the attention of the pharmaceutical industry as a powerful mechanism for the discovery of novel drug-like hits for various biological targets. Nuevolution Chemetics technology enables DNA-encoded synthesis of billions of chemically diverse drug-like small molecule compounds, and the efficient screening and optimization of these, facilitating effective identification of drug candidates at an unprecedented speed and scale. Although many approaches have been developed by the cheminformatics community for the analysis and visualization of drug-like chemical space, most of them are restricted to the analysis of a maximum of a few millions of compounds and cannot handle collections of 10 8 -10 12 compounds typical for DELs. To address this big chemical data challenge, we developed the Reduced Complexity Molecular Frameworks (RCMF) methodology as an abstract and very general way of representing chemical structures. By further introducing RCMF descriptors, we constructed a global framework map of drug-like chemical space and demonstrated how chemical space occupied by multi-million-member drug-like Chemetics DNA-encoded libraries and virtual combinatorial libraries with >10 12 members could be analyzed and mapped without a need for library enumeration. We further validate the approach by performing RCMF-based searches in a drug-like chemical universe and mapping Chemetics library selection outputs for LSD1 targets on a global framework chemical space map.

Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.

PubMed

Ponti, G; Ponz de Leon, M; Maffei, S; Pedroni, M; Losi, L; Di Gregorio, C; Gismondi, V; Scarselli, A; Benatti, P; Roncari, B; Seidenari, S; Pellacani, G; Varotti, C; Prete, E; Varesco, L; Roncucci, L

2005-11-01

Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.Peculiar dermatologic manifestations are present in several heritable gastrointestinal disorders. Muir-Torre syndrome (MTS) is a genodermatosis whose peculiar feature is the presence of sebaceous gland tumors associated with visceral malignancies. We describe one patient in whom multiple sebaceous gland tumors were associated with early onset colon and thyroid cancers and attenuated polyposis coli. Her family history was positive for colonic adenomas. She had a daughter presenting with yellow papules in the forehead region developed in the late infancy. Skin and visceral neoplasms were tested for microsatellite instability and immunohistochemical status of mismatch repair (MMR), APC and MYH proteins. The proband colon and skin tumors were microsatellite stable and showed normal expression of MMR proteins. Cytoplasmic expression of MYH protein was revealed in colonic cancer cells. Compound heterozygosity due to biallelic mutations in MYH, R168H and 379delC, was identified in the proband. The 11-year-old daughter was carrier of the monoallelic constitutional mutation 379delC in the MYH gene; in the sister, the R168H MYH gene mutation was detected. This report presents an interesting case of association between MYH-associated polyposis and sebaceous gland tumors. These findings suggest that patients with MTS phenotype that include colonic polyposis should be screened for MYH gene mutations.

Development cooperation in water and sanitation: is it based on the human rights framework?

PubMed

Brown, Colin; Heller, Léo

2017-07-01

The water and sanitation sector is verifiably receiving increased attention and funding through international development cooperation. Not least because of the way that it affects incentives and institutions in partner countries, development cooperation can have either positive or negative effects on human rights though. The consolidated frameworks for the human rights to water and sanitation is becoming linked to the international community's coordinated development efforts, as evidenced notably in the 2030 Agenda for Sustainable Development. However, a review of major funders' official policies for development cooperation in the sector suggests that many only partially endorse the frameworks for the human rights to water and sanitation. An observation of development cooperation flows to the sector allows the hypothesis to be advanced that worldwide inequalities in access to these services may be reduced through a full and clear application of the human rights framework in development cooperation activities. The article presents findings of this research and explores key stakes for development cooperation in the water and sanitation sector that are relevant for their ability to either negatively or positively contribute to the realization of human rights. Resumen El sector de agua y saneamiento ha recibido creciente atención y financiación a través de la cooperación internacional para el desarrollo. La cooperación para el desarrollo puede tener efectos tanto positivos cuanto negativos sobre los derechos humanos. El hito que consolida los derechos humanos al agua y al saneamiento están articulados a esfuerzos de cooperación para el desarrollo promovidos por la comunidad internacional, como se evidencia en la Agenda 2030 para el Desarrollo Sostenible. Sin embargo, una revisión de las políticas oficiales de los principales financiadores del sector sugiere que muchos de ellos aprueban solo parcialmente los hitos de los derechos humanos al agua y el saneamiento. La observación de los flujos de esta cooperación para el sector permite formular la hipótesis de que las desigualdades en el acceso a estos servicios en diferentes partes del mundo pueden reducirse con la aplicación completa y clara del marco de los derechos humanos en las actividades de cooperación para el desarrollo. El artículo presenta los resultados de esta investigación y explora los desafíos de la cooperación para el desarrollo del sector de agua y aguas residuales que son relevantes para impactar tanto negativamente cuanto positivamente a los derechos humanos.

[Not Available].

PubMed

Peñailillo Escarate, Luis; Mackay Phillips, Karen; Serrano Duarte, Natalia; Canales Espinoza, Pablo; Miranda Herrera, Pamela; Zbinden-Foncea, Hermann

2016-07-19

Introducción: el entrenamiento de intervalos de alta intensidad (HIIT) y el consumo de ácidos grasos omega-3 (O3) ha demostrado cada uno por separado aumentar la capacidad aeróbica, metabolismo oxidativo y función cardiovascular.Objetivo: examinar el efecto combinado de HIIT más suplementación de O3 en el rendimiento físico, presión arterial y composición corporal en jóvenes sedentarios.Método: 28 jóvenes sedentarios con sobrepeso (Edad=22 ± 4 años; IMC=25.8 ± 2.4 kg·m-2) fueron distribuidos aleatoriamente en cuatro grupos: grupo O3/HIIT (n=7) realizó un protocolo de HIIT, tres veces por semana durante seis semanas y consumió 2 g·día-1 de O3; grupo HIIT (n=7) realizó solo el HIIT; grupo O3 (n=7) solo consumió O3; y grupo CONTROL (n=7) que no realizó ninguna intervención. Consumo de oxígeno peak (VO2peak), velocidad máxima (Vmax), presión arterial sistólica y diastólica (PAS y PAD), y porcentaje de grasa fueron medidos antes y después de la intervención.Resultados: el consumo de oxígeno peak aumentó más en el grupo O3/HIIT (+10.9%) en comparación con HIIT, O3 y CONTROL. Velocidad máxima aumentó en O3/HIIT (+7.1%) y HIIT (+11.9%). La presión arterial sistólica disminuyó más en O3 (-6.8%) en comparación con O3/HIIT, HIIT y CONTROL. Por último, O3/HIIT (-19.2%), HIIT (-20.2%), y O3 (-15.2%) presentaron mayores disminuciones del porcentaje de masa grasa en relación al CONTROL.Conclusión: nuestros resultados sugieren un efecto potenciador de la capacidad aeróbica máxima producto de la combinación de HIIT y suplementación de O3. Además, se observó una disminución de masa grasa en todos los grupos intervenidos.

Short communication: novel truncating mutations in the CFTR gene causing a severe form of cystic fibrosis in Italian patients.

PubMed

Lenarduzzi, S; Morgutti, M; Crovella, S; Coiana, A; Rosatelli, M C

2014-11-14

Cystic fibrosis (CF) is a common recessive genetic disease caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. More than 1800 different mutations have been described to date. Here, we report 3 novel mutations in CFTR in 3 Italian CF patients. To detect and identify 36 frequent mutations in Caucasians, we used the INNO-LiPA CFTR19 and INNO-LiPA CFTR17+Tn Update kits (Innogenetics; Ghent, Belgium). Our first analysis did not reveal both of the responsible mutations; thus, direct sequencing of the CFTR gene coding region was performed. The 3 patients were compound heterozygous. In one allele, the F508del (c.1521_1523delCTT, p.PHE508del) mutation in exon 11 was observed in each case. For the second allele, in patient No.1, direct sequencing revealed an 11-base pair deletion (GAGGCGATACT) in exon 14 (c.2236_2246del; pGlu746Alafs*29). In patient No. 2, direct sequencing revealed a nonsense mutation at nucleotide 3892 (c.3892G>T) in exon 24. In patient No. 3, direct sequencing revealed a deletion of cytosine in exon 27 (c.4296delC; p.Asn1432Lysfs*16). These 3 novel mutations indicate the production of a truncated protein, which consequently results in a non-functional polypeptide.

Are Japanese groups more competitive than Japanese individuals? A cross-cultural validation of the interindividual-intergroup discontinuity effect.

PubMed

Takemura, Kosuke; Yuki, Masaki

2007-02-01

The interindividual-intergroup discontinuity effect is the tendency for relationships between groups to be more competitive than the relationships between individuals. It has been observed robustly in studies conducted in the United States, which is a society characterized as "individualistic." In this study, it was explored whether the effect was replicable in a "collectivistic" society such as Japan. From the traditional view in cross-cultural psychology, which emphasizes the collectivistic nature of East Asian peoples, it was expected that the discontinuity effect would be greater in Japan than in the United States. On the other hand, based on recent empirical findings suggesting that North Americans are no less group-oriented than East Asians, it was expected that the discontinuity effect would be no greater in Japan than in the United States. One hundred and sixty Japanese university students played a 10-trial repeated prisoner's dilemma game: 26 sessions of interindividual and 18 sessions of intergroup. Following exactly the procedure of prior experiments in the US, individuals and groups were allowed face-to-face communication with their opponents before making their decisions, and participants in the intergroup condition were further allowed to converse freely with their in-group members. Results replicated previous findings in the United States; groups made more competitive choices than did individuals. In addition, neither the magnitude of the discontinuity effect, nor the frequency of competitive choices made by the groups, were larger in Japan than they were in the majority of prior studies conducted in the United States. These findings suggest cross-cultural robustness of the interindividual-intergroup discontinuity effect. Also, interestingly, they contradict the simple distinction between individualism and collectivism. Implications for studies of culture and group processes are discussed. This research was supported by grants from the Center for the Study of Cultural and Ecological Foundations of the Mind, a 21(st) Century Center of Excellence Program at Hokkaido University. The authors would like to thank Dr. Laura Hernández-Guzmán, three anonymous reviewers, and Robin Cooper, Mark H. B. Radford, and Paul A. Wehr for their helpful comments on earlier versions of this article. They would also like to thank Dr. Chester A. Insko for his kind and valuable advice during the planning of this experiment as well as the interpretation of its results, Kaori Akaishi for her help with data collection, and, finally, colleagues at Hokkaido University who helped to recruit potential participants from their classes. L'effet de discontinuité entre les individus et entre les groupes est la tendance des relations entre les groupes à être plus compétitives que les relations entre les individus. Cet effet fut fermement démontré dans des études menées aux États-Unis, une société caractérisée d' «individualiste». Dans la présente étude, nous avons exploré dans quelle mesure l'effet était applicable à une société «collectiviste» comme le Japon. À partir du point de vue traditionnel de la psychologie interculturelle, laquelle met l'emphase sur la nature collectiviste des peuples de l'Asie de l'Est, il était attendu que l'effet de discontinuité allait être plus grand au Japon qu'aux États-Unis. D'un autre côté, se basant sur les données empiriques récentes qui suggèrent que les Nord-américains ne sont pas moins orientés vers le groupe que les Asiatiques de l'Est, il était attendu que l'effet de discontinuité ne serait pas plus important au Japon qu'aux États-Unis. Cent soixante étudiants universitaires japonais ont pris part à un jeu de dilemme de prisonnier de 10 essais répétés: 26 sessions entre individus et 18 sessions entre groupes. Suivant exactement la procédure des expériences menées précédemment aux États-Unis, les individus et les groupes avaient la permission de communiquer face-à-face avec leur opposant avant de prendre leur décision. De plus, les participants de la condition entre groupes avaient également la possibilité de converser librement avec les membres de leur propre groupe. Les résultats se sont révélés semblables à ceux des études antérieures réalisées aux États-Unis; les groupes ont fait des choix plus compétitifs que les individus. En outre, ni la magnitude de l'effet de discontinuité, ni la fréquence des choix compétitifs faits par les groupes n'étaient plus grands chez les Japonais comparativement à la majorité des études antérieures menées aux États-Unis. Ces résultats soutiennent la robustesse interculturelle de l'effet de discontinuité entre les individus et entre les groupes. Aussi, fait intéressant, ils contredisent la simple distinction entre l'individualisme et le collectivisme. Les implications pour des études sur les cultures et les processus de groupe sont discutées. El efecto de discontinuidad entre individuos y entre grupos es la tendencia a que las relaciones entre grupos sean más competitivas que las relaciones entre individuos. Se ha observado con insistencia en estudios conducidos en Estados Unidos, una sociedad caracterizada como "individualista". En el presente estudio, se exploró si el efecto se repetía en una sociedad "colectivista" como la japonesa. Desde la perspectiva tradicional de la psicología trans cultural, que subraya la naturaleza colectivista de los pueblos asiáticos, se esperaba que el efecto de discontinuidad fuese mayor en Japón que en Estados Unidos. Por otra parte, con base en los hallazgos empíricos recientes que sugieren que los estadounidenses no están menos orientados al grupo que los de este asiático, se esperaba que el efecto de discontinuidad no fuera mayor en Japón que en los Estados Unidos. Ciento sesenta estudiantes universitarios japoneses participaron en un juego del dilema de un prisionero de diez ensayos repetidos: veintiséis sesiones entre individuos y diez y ocho entre grupos. Siguiendo exactamente el procedimiento de los experimentos previos en los Estados Unidos, se permitió tanto a los individuos como a los grupos una comunicación cara a cara con sus oponentes antes de tomar sus decisiones, y se permitió a los participantes en la condición entre grupos que conversaran libremente con los miembros de su propio grupo. Los resultados repitieron los hallazgos previos en los Estados Unidos; los grupos hicieron elecciones más competitivas que los individuos. Además, ni la magnitud del efecto de discontinuidad ni la frecuencia de las elecciones competitivas de los grupos, fueron mayores en Japón que en la mayoría de los estudios previos en Estados Unidos. Estos hallazgos sugieren la robustez trans cultural del efecto de discontinuidad entre individuos y entre grupos. También, de manera interesante, contradicen la simple distinción entre individualismo y colectivismo. Se discutieron las implicaciones para los estudios sobre cultura y procesos grupales.

Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation.

PubMed

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2011-03-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. Copyright © 2011 Wiley-Liss, Inc.

Hereditary Hypophosphatemic Rickets With Hypercalciuria and Nephrolithiasis—Identification of a Novel SLC34A3/NaPi-IIc Mutation

PubMed Central

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2015-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient’s mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2–6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. PMID:21344632

Effectiveness of personalized face-to-face and telephone nursing counseling interventions for cardiovascular risk factors: a controlled clinical trial.

PubMed

Vílchez Barboza, Vivian; Klijn, Tatiana Paravic; Salazar Molina, Alide; Sáez Carrillo, Katia Lorena

2016-08-08

to evaluate the effect and gender differences of an innovative intervention involving in-person and telephone nursing counseling to control cardiovascular risk factors (arterial hypertension, dyslipidemia, and overweight), improve health-related quality of life and strengthen self-efficacy and social support in persons using the municipal health centers' cardiovascular health program. a randomized controlled clinical trial involving participants randomized into the intervention group who received traditional consultation plus personalized and telephone nursing counseling for 7 months (n = 53) and the control group (n = 56). The study followed the Consolidated Standards of Reporting Trials Statement. women in the intervention group presented a significant increase in the physical and mental health components compared to the control group, with decreases in weight, abdominal circumference, total cholesterol, low-density lipoprotein cholesterol, and the atherogenic index. The effects attributable to the intervention in the men in the intervention group were increased physical and emotional roles and decreased systolic and diastolic pressure, waist circumference, total cholesterol, low-density lipoprotein cholesterol, atherogenic index, cardiovascular risk factor, and 10-year coronary risk. this intervention is an effective strategy for the control of three cardiovascular risk factors and the improvement of health-related quality of life. evaluar efecto y diferencias por sexo de una intervención innovadora "Consejería de Enfermería Personalizada y Telefónica", dirigida al control de factores de riesgo cardiovascular (hipertensión arterial, dislipidemia y sobrepeso) y al mejoramiento de la calidad de vida relacionada con la salud, fortaleciendo la autoeficacia y el apoyo social en personas usuarias del programa de salud cardiovascular de los Centros de Salud Municipales de Concepción. ensayo clínico controlado aleatoriamente y selección aleatoria de participantes; grupo intervención con consulta tradicional más consejería de enfermería personalizada y telefónica durante 7 meses (n=53); y grupo control (n=56); siguiendo la declaración del Consolidated Standards of Reporting Trials. mujeres del grupo intervención, presentaron aumento significativo con respecto al grupo control, en componentes de salud física y mental; disminución de: peso, circunferencia abdominal, colesterol total, colesterol lipoproteínas de baja densidad e índice de aterogenicidad. En hombres del grupo intervención se reflejó como efectos atribuibles a la intervención: 1) aumento en dimensiones del rol físico y emocional; 2) disminución: presión sistólica y diastólica, circunferencia abdominal, colesterol total, colesterol lipoproteínas de baja densidad, índice de aterogenicidad, factor de riesgo cardiovascular y riesgo coronario a 10 años. esta intervención es una estrategia efectiva para el control de tres factores de riesgo cardiovascular y mejoría de calidad de vida relacionada con la salud. avaliar o efeito e as diferenças por sexo de uma intervenção inovadora: o aconselhamento personalizado e por telefone em enfermagem, visando o controle de fatores de risco cardiovascular (hipertensão arterial, dislipidemia e sobrepeso) e a melhora na qualidade de vida relacionada à saúde, fortalecendo a autoeficácia e o apoio social a pessoas que usam o programa de saúde cardiovascular de Centros Municipais de Saúde. ensaio clínico controlado e randomizado, participantes randomizados, grupo de intervenção: consulta tradicional mais aconselhamento personalizado e por telefone em enfermagem por 7 meses (n = 53); e grupo de controle (n = 56); seguindo a declaração Consolidated Standards of Reporting Trials Statement. mulheres do grupo intervenção apresentaram um aumento significativo, em relação ao grupo controle, nos componentes de saúde mental e física, com diminuição do peso, circunferência abdominal, colesterol total, colesterol de lipoproteínas de baixa densidade e índice aterogênico. Em homens do grupo intervenção, os efeitos atribuíveis à intervenção foram: aumentos nos papeis físicos e emocionais, com diminuições na pressão sistólica e diastólica, circunferência abdominal, colesterol total, colesterol de lipoproteínas de baixa densidade, índice aterogênico, fator de risco cardiovascular e risco coronariano em 10 anos. essa intervenção é uma estratégia eficaz para o controle dos três fatores de risco cardiovascular e a melhora da qualidade de vida relacionada à saúde.

DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target Interaction Prediction

PubMed Central

Jiang, Jinjian; Wang, Nian; Zhang, Jun

2017-01-01

Background Drug-target interaction is key in drug discovery, especially in the design of new lead compound. However, the work to find a new lead compound for a specific target is complicated and hard, and it always leads to many mistakes. Therefore computational techniques are commonly adopted in drug design, which can save time and costs to a significant extent. Results To address the issue, a new prediction system is proposed in this work to identify drug-target interaction. First, drug-target pairs are encoded with a fragment technique and the software “PaDEL-Descriptor.” The fragment technique is for encoding target proteins, which divides each protein sequence into several fragments in order and encodes each fragment with several physiochemical properties of amino acids. The software “PaDEL-Descriptor” creates encoding vectors for drug molecules. Second, the dataset of drug-target pairs is resampled and several overlapped subsets are obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build an ensemble system. Conclusion Experimental results on the drug-target dataset showed that our method performs better and runs faster than the state-of-the-art predictors. PMID:28744468

Propiedades biomecánicas de la membrana limitante interna tras recibir tratamiento intravítreo con ocriplasmina.

PubMed

Vielmuth, Franziska; Schumann, Ricarda G; Spindler, Volker; Wolf, Armin; Scheler, Renate; Mayer, Wolfgang J; Henrich, Paul B; Haritoglou, Christos

2017-01-01

Objetivo: Evaluar la rigidez de la membrana limitante interna (MLI) humana y evaluar los posibles cambios de las propiedades mecánicas tras administrar una inyección intravítrea de ocriplasmina para tratar la tracción vitreomacular. Métodos: Este estudio se compone de una serie de casos intervencionales y comparativos de 12 muestras de MLI extraídas mediante cirugía y obtenidas de forma consecutiva de 9 ojos de 9 pacientes después de someterse sin éxito a vitreólisis farmacológica con ocriplasmina. Durante el mismo periodo de tiempo, 16 muestras de otros 13 ojos sin tratamiento con ocriplasmina se obtuvieron mediante vitrectomía y sirvieron como controles. Todos los pacientes presentaron agujeros maculares o tracción vitreomacular y se sometieron a vitrectomía con disección de la MLI tanto con tinción con azul brillante (AB) como sin ella. Todas las muestras se analizaron con un microscopio de fuerza atómica con imágenes de las regiones de 25 × 25 μm. En todas las muestras, se analizaron tanto la parte de la retina como la del vítreo de la MLI. Resultados: La microscopia de fuerza atómica no reveló diferencias significativas en cuanto a elasticidad de las muestras de MLI extraídas de ojos con o sin tratamiento con ocriplasmina. Las áreas onduladas de la parte de la retina presentaron una mayor rigidez que la parte del vítreo de la MLI. La cartografía topográfica tanto de la parte del vítreo como de la retina de la MLI no mostró ninguna alteración aparente de la morfología en ojos tratados con ocriplasmina en comparación con los ojos no tratados. La tinción con azul brillante conllevó un aumento de la rigidez tisular. Conclusiones: Las inyecciones intravítreas de ocriplasmina no varían las propiedades biomecánicas de la MLI humana. No existen pruebas de un posible efecto enzimático que interfiera con la rigidez de esta membrana basal. © 2017 S. Karger AG, Basel.

Induction of sterility in Anastrepha Fraterculus (Diptera: Tephritidae) by gamma radiation

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

Allinghi, A.; Gramajo, C.; Willink, E.

In relation to the application of the sterile insect technique (SIT) for the South American fruit fly Anastrepha fraterculus (Wiedemann), we analyzed the effect on adult fertility of different doses of gamma irradiation and the age of pupae at the time of irradiation. In a first experiment, we applied doses of 50, 70, and 90 Gy to pupae at 24, 48, 72, and 96 h before adult emergence. In a second experiment we irradiated pupae 48 h before emergence with 20, 40, and 60 Gy and estimated male and female fertility and sperm transfer by irradiated males. The results indicatedmore » pupal age at irradiation does not significantly affect male fertility. If males irradiated with 60 Gy are crossed to non-irradiated females the fertility is about 1%. Females irradiated with 40 Gy did not lay eggs independently of the male to which they mated. No significant effects of radiation were observed with respect to the ability of males to transfer sperm. A dose of 70 Gy applied 48 h before adult emergence induces 100% sterility in both males and females. (author) [Spanish] Para la aplicacion de la tecnica del insecto esteril (TIE) en Anastrepha fraterculus (Wiedemann), en este trabajo analizamos el efecto de diferentes dosis de irradiacion gamma y la edad optima de la pupa al momento de la irradiacion. En el primer experimento se evaluaron las dosis de 50, 70, y 90 Gy en pupas de 24, 48, 72, y 96 h antes de la emergencia del adulto. En el segundo experimento se irradiaron pupas 48 h antes de la emergencia con dosis de 20, 40, 60 Gy y se estimo la fertilidad de los machos y las hembras, y la transferencia de espermas por los machos irradiados. Los resultados indicaron que la irradiacion no modifico significativamente la fertilidad de los machos. En las cruzas de machos irradiados a 60 Gy con hembras no irradiadas se observo 1% de eclosion larvaria, mientras que las hembras irradiadas a 40 Gy no pusieron huevos. La irradiacion no afecto significativamente la transferencia de espermas de los machos tratados. Por lo tanto, una dosis de 70 Gy aplicada 48 h antes de la emergencia del adulto induce 100% de esterilidad tanto en machos como en hembras. (a0011uth.« less

La enumeración de la soltería femenina en los censos de población: sesgo y propuesta de corrección

PubMed Central

McCaa, Robert; Esteve, Albert; Garcia, Joan

2013-01-01

Esta investigación tiene como objetivo investigar el efecto que la disolución de las uniones consensuales tiene en los niveles de soltería que proporciona el Censo de Población, niveles derivados de la variable estado civil. Para ello comparamos los datos censales con los de la Encuestas de Demografía y Salud (de ahora en adelante DHS) en aquellos países y años para los que disponemos de ambas fuentes en el mismo año o años adyacentes (Bolivia, Brasil, Colombia y Perú). Los resultados muestran claramente que las proporciones de nunca unidas derivadas de la variable censal ’Estado civil’ son sistemáticamente más elevadas que las estimadas a partir de las DHS. La razón de esta sobreestimación obedece al hecho de que personas que estuvieron en unión libre en el pasado se declaran solteras en el momento del Censo. La elevada proporción de mujeres solteras que tienen hijos según el Censo es una prueba de ello y a su vez una solución efectiva para corregir el sesgo. PMID:25593515

Determination of aquifer roof extending under the sea from variable-density flow modelling of groundwater response to tidal loading: case study of the Jahe River Basin, Shandong Province, China

NASA Astrophysics Data System (ADS)

Cheng, Jianmei; Chen, Chongxi; Ji, Menrui

The main task of studies on salt-water intrusion into coastal confined aquifers is to predict the position of the fresh- salt-water interface, which can be determined from the length of the aquifer roof extending under the sea. Records of groundwater level affected by tides can be used to infer hydrological conditions and determine hydraulic parameters of an aquifer extending under the sea. In this paper, a three-dimensional, variable-density groundwater flow model has been developed to determine the equivalent roof length of an aquifer extending under the sea from the tidal-effected data of groundwater level in the Jahe River Basin, Shandong Province, China. The seaward boundary is obtained by converging hydraulic head fluctuations observed in drill holes with calculated values, and the aquifer parameters in the extending zone are estimated. The impacts of aquifer roof length and aquifer parameters on the fluctuation of tidal groundwater are studied. It is concluded that the length of the aquifer roof extending under the sea should correspond with certain aquifer parameters in the extrapolation zone. Therefore, the seaward boundary determined from tidal-effect information is the equivalent boundary in hydrodynamic characteristics rather than the true boundary of the confined aquifer Les sujets principaux des études d'instrusion saline dans les aquifères confinés en zone côtière sont la prédiction de la position de l'interface entre l'eau salée et l'eau fraîche, qui peut être déterminée à partir de l'extention du toit de l'aquifère sous la mer. Les enregistrements des niveaux des eaux souterraines influencés par les marées peuvent être utilisés pour préciser les conditions hydrologiques et déterminer les paramètres hydrauliques d'un aquifère possédant une extension sous la mer. Dans cet article, un modèle tridimensionnel comprenant des eaux souterraines de densité variable a été développé pour déterminer la longueur équivalente du toit d'un aquifère qui s'étend sous la mer à partir des données concernant les effets de marée sur les eaux souterraines dans le bassin de la rivière Jahe, dans la province de Shandong, Chine. La limite de salinité est déterminée en faisant converger les fluctuations des hauteurs piézométriques avec les valeurs calculées, et les paramètres de l'aquifère sont estimés dans la zone s'étendant sous la mer. L'incidence de la longueur de l'aquifère sous la mer sur les fluctuations des niveaux est étudiée. On en conclut que la longueur du toit de l'aquifère sous la mer peut correspondre à certains aquifères paramètres dans la zone d'extrapolation. Par conséquent, la limite de salinité déterminée à partir des effets de marée est l'équivalent d'une limite hydrodynamique plutôt que la véritable limite de l'aquifère. El principal objetivo de los estudios sobre intrusiones de agua salada en acuíferos costeros confinados es predecir la posición de la interfase agua dulce-agua salada, la cual puede determinarse a partir de la longitud del techo del acuífero que se extiende por debajo del mar. Los registros de niveles de agua subterránea afectados por las mareas puede utilizarse para inferir las condiciones hidrológicas y determinar los parámetros hidráulicos de un acuífero que se extiende por debajo del mar. En este artículo se ha desarrollado un modelo de flujo tri-dimensional de agua subterránea de densidad variable para determinar la longitud del techo equivalente de un acuífero que se extiende por debajo del mar a partir de datos, afectados por la marea, de niveles de agua subterránea en la Cuenca del Río Jahe, Provincia Shandong, China. El límite hacia el océano se obtiene por convergencia de fluctuaciones de presiones hidráulicas observadas en pozos con valores calculados, y se estiman los parámetros del acuífero en la zona extendida. Se estudian los impactos de la longitud del techo del acuífero y los parámetros del acuífero en la fluctuación del agua subterránea afectada por las mareas. Se concluye que la longitud del techo del acuífero que se extiende por debajo del mar debería corresponder con ciertos parámetros del acuífero en la zona de extrapolación. Por lo tanto, el límite hacia el océano determinado a partir de información de efectos de marea es el límite equivalente en características hidrodinámicas más que el límite real del acuífero confinado.

Tools for evaluating Lipolexis oregmae (Hymenoptera: Aphidiidae) in the field: Effects of host aphid and host plant on mummy location and color plus improved methods for obtaining adults

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

Singh, R.; Hoy, M.A.

Lipolexis oregmae Gahan was introduced into Florida in a classical biological control program directed against the brown citrus aphid, Toxoptera citricida (Kirkaldy), on citrus. Prior to evaluating distribution, host range, and potential nontarget effects of L. oregmae in Florida, we evaluated the role of other potential host aphids and host plants on mummy production and location. Under laboratory conditions, this parasitoid produced the most progeny on the target pest, the brown citrus aphid on citrus. This parasitoid, unlike the majority of aphidiids, did not produce mummies on any of the host plants tested when reared in black citrus aphid T.more » aurantii (Boyer de Fonscolombe) on grapefruit, spirea aphid Aphis spiraecola Patch on grapefruit and pittosporum, cowpea aphid A. craccivora Koch on grapefruit and cowpeas, or melon aphid A. gossypii Glover on grapefruit and cucumber. Thus, sampling for L. oregmae mummies of these host aphids and host plants must involve holding foliage in the laboratory until mummies are produced. This parasitoid requires high relative humidity to produce adults because no adults emerged when mummies were held in gelatin capsules, but high rates of emergence were observed when mummies were held on 1.5% agar plates. In addition, we compared the color of 6 aphid hosts and the color of mummies produced by L. oregmae when reared in them to determine if color of mummies could be used to identify L. oregmae . Mummy color varied between aphid hosts and tested host plants, and is not a useful tool for identifying L. oregmae for nontarget effects. (author) [Spanish] Lipolexis oregmae Gahan fue introducida en Florida por medio de un programa de control biologico clasico dirigido contra el afido pardo de los citricos, Toxoptera citricida (Kirkaldy), sobre Citrus. Prioritario a la evaluacion de la distribucion, el rango de los hospederos y los efectos potenciales de L. oregmae sobre los organismos que no son el enfoque de control en la Florida, nosotros evaluamos el papel de otras especies de afidos y plantas hospederas potenciales sobre la produccion y ubicacion de las momias. Bajo condiciones de laboratorio, este parasitoide produjo el mayor numero de progenies sobre la especie de plaga enfocada, el afido pardo de los citricos sobre Citrus . Este parasitoide, no como la mayoria de los afidiidos (Hymenoptera), no produjo momias sobre cualquiera de las plantas hospederas probadas cuando fue criado sobre el afido negro de los citricos, ( T. aurantii (Boyer de Fonscolombe)) en toronja, el afido spirea (Aphis spiraecola Patch) en toronja y pittosporum, el afido del caupi (A. craccivora Koch) en toronja y caupi o el afido del melon (A. gossypii Glover) en toronja y pepino. Asi, el muestreo para momias de L. oregmae de estas especies de afidos hospederos y plantas hospederas tiene que incluir el mantenimiento de follaje en el laboratorio hasta que se produzcan las momias. Este parasitoide requiere una alta humedad relativa para producir los adultos por que ningun adulto emergio cuando las momias fueron mantenidas en capsulas de gelatina, pero una tasa alta de emergencia de adultos fue observada cuando se mantuvo las momias en platos con agar al 1.5%. Ademas de esto, nosotros comparamos el color de 6 especies de afidos hospederos, asi como el color de las momias producidos por L. oregmae cuando fue criado sobre ellos para determinar si se puede usar el color de las momias para la identificacion de L. oregmae . El color de las momias varia entre las especies de afidos hospederos y las plantas hospederas probadas, por lo que no es una herramienta util para la identificacion de L. oregmae o para la evaluacion de su efecto sobre los organismos que no son el enfoque del control. (author)« less

Antibacterial Activity, Antioxidant Effect and Chemical Composition of Propolis from the Región del Maule, Central Chile.

PubMed

Nina, Nélida; Quispe, Cristina; Jiménez-Aspee, Felipe; Theoduloz, Cristina; Feresín, Gabriela Egly; Lima, Beatriz; Leiva, Elba; Schmeda-Hirschmann, Guillermo

2015-10-06

Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (-) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis.

The importance of being kinked: role of Pro residues in the selectivity of the helical antimicrobial peptide P5.

PubMed

Bobone, Sara; Bocchinfuso, Gianfranco; Park, Yoonkyung; Palleschi, Antonio; Hahm, Kyung-Soo; Stella, Lorenzo

2013-12-01

Antimicrobial peptides (AMPs) are promising compounds for developing new antibiotic drugs against drug-resistant bacteria. Many of them kill bacteria by perturbing their membranes but exhibit no significant toxicity towards eukaryotic cells. The identification of the features responsible for this selectivity is essential for their pharmacological development. AMPs exhibit few conserved features, but a statistical analysis of an AMP sequence database indicated that many α-helical AMPs surprisingly have a helix-breaking Pro residue in the middle of their sequence. To discriminate among the different possible hypotheses for the functional role of this feature, we designed an analogue of the antimicrobial peptide P5, in which the central Pro was deleted (analogue P5Del). Pro removal resulted in a dramatic increase of toxicity. This was explained by the observation that P5Del binds both charged and neutral membranes, whereas P5 has no appreciable affinity towards neutral bilayers. CD and simulative data provided a rationalization of this behavior. In solution P5, due to the presence of Pro, attains compact conformations, in which its apolar residues are partially shielded from the solvent, whereas P5Del is more helical. These structural differences reduce the hydrophobic driving force for association of P5 to neutral membranes, whereas its binding to anionic bilayers can still take place because of electrostatic attraction. After membrane binding, the Pro residue does not preclude the attainment of a membrane-active amphiphilic helical conformation. These findings shed light on the role of Pro residues in the selectivity of AMPs and provide hints for the design of new, highly selective compounds. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Nonspherical Radiation Driven Wind Models Applied to Be Stars

NASA Astrophysics Data System (ADS)

Arauxo, F. X.

1990-11-01

ABSTRACT. In this work we present a model for the structure of a radiatively driven wind in the meridional plane of a hot star. Rotation effects and simulation of viscous forces were included in the motion equations. The line radiation force is considered with the inclusion of the finite disk correction in self-consistent computations which also contain gravity darkening as well as distortion of the star by rotation. An application to a typical BlV star leads to mass-flux ratios between equator and pole of the order of 10 and mass loss rates in the range 5.l0 to Mo/yr. Our envelope models are flattened towards the equator and the wind terminal velocities in that region are rather high (1000 Km/s). However, in the region near the star the equatorial velocity field is dominated by rotation. RESUMEN. Se presenta un modelo de la estructura de un viento empujado radiativamente en el plano meridional de una estrella caliente. Se incluyeron en las ecuaciones de movimiento los efectos de rotaci6n y la simulaci6n de fuerzas viscosas. Se consider6 la fuerza de las lineas de radiaci6n incluyendo la correcci6n de disco finito en calculos autoconsistentes los cuales incluyen oscurecimiento gravitacional asi como distorsi6n de la estrella por rotaci6n. La aplicaci6n a una estrella tipica BlV lleva a cocientes de flujo de masa entre el ecuador y el polo del orden de 10 de perdida de masa en el intervalo 5.l0 a 10 Mo/ano. Nuestros modelos de envolvente estan achatados hacia el ecuador y las velocidads terminales del viento en esa regi6n son bastante altas (1000 Km/s). Sin embargo, en la regi6n cercana a la estrella el campo de velocidad ecuatorial esta dominado por la rotaci6n. Key words: STARS-BE -- STARS-WINDS

Interactive effects of water diversion and climate change for juvenile chinook salmon in the lemhi river basin (USA.).

PubMed

Walters, Annika W; Bartz, Krista K; McClure, Michelle M

2013-12-01

The combined effects of water diversion and climate change are a major conservation challenge for freshwater ecosystems. In the Lemhi Basin, Idaho (U.S.A.), water diversion causes changes in streamflow, and climate change will further affect streamflow and temperature. Shifts in streamflow and temperature regimes can affect juvenile salmon growth, movement, and survival. We examined the potential effects of water diversion and climate change on juvenile Chinook salmon (Oncorhynchus tshawytscha), a species listed as threatened under the U.S. Endangered Species Act (ESA). To examine the effects for juvenile survival, we created a model relating 19 years of juvenile survival data to streamflow and temperature and found spring streamflow and summer temperature were good predictors of juvenile survival. We used these models to project juvenile survival for 15 diversion and climate-change scenarios. Projected survival was 42-58% lower when streamflows were diverted than when streamflows were undiverted. For diverted streamflows, 2040 climate-change scenarios (ECHO-G and CGCM3.1 T47) resulted in an additional 11-39% decrease in survival. We also created models relating habitat carrying capacity to streamflow and made projections for diversion and climate-change scenarios. Habitat carrying capacity estimated for diverted streamflows was 17-58% lower than for undiverted streamflows. Climate-change scenarios resulted in additional decreases in carrying capacity for the dry (ECHO-G) climate model. Our results indicate climate change will likely pose an additional stressor that should be considered when evaluating the effects of anthropogenic actions on salmon population status. Thus, this type of analysis will be especially important for evaluating effects of specific actions on a particular species. Efectos Interactivos de la Desviación del Agua y el Cambio Climático en Individuos Juveniles de Salmón Chinook en la Cuenca del Río Lemhi (E.U.A.). Conservation Biology © 2013 Society for Conservation Biology No claim to original US government works.

A novel sterane, 27-nor-24-methyl-5α-cholestane, in sediments

NASA Astrophysics Data System (ADS)

Schouten, Stefan; Sinninghe Damsté, Jaap S.; Schoell, Martin; de Leeuw, Jan W.

1994-09-01

A novel sterane, 27-nor-24-methyl-5α-cholestane, has been identified in sedimentary hydrocarbon mixtures by coinjection with an authentic standard. The C27 sterane occurs in silica-rich sediments from the Monterey Formation, USA, the Onnagawa Formation, Japan, and the Menilite Shale, Poland, and in bituminous marls from the Vena del Gesso basin, Italy. The compound seems to be biosynthetically related to 24-norcholestanes which co-occurs in sometimes relatively high amounts. The 13C-content of the sterane in the Monterey Formation indicates an algal source similar to other steranes present in this sediment. A diatom or a dinoflagellate source is suggested for this compound.

Prevalence of GJB2 (connexin-26) and GJB6 (connexin-30) mutations in a cohort of 300 Brazilian hearing-impaired individuals: implications for diagnosis and genetic counseling.

PubMed

Batissoco, Ana Carla; Abreu-Silva, Ronaldo Serafim; Braga, Maria Cristina Célia; Lezirovitz, Karina; Della-Rosa, Valter; Alfredo, Tabith; Otto, Paulo Alberto; Mingroni-Netto, Regina Célia

2009-02-01

Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness. Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6-D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected c.167delT, p.Trp24X, p.Val37Ile, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro. Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27Ile, p.Met34Thr, p.Ala40Ala, and p.Gly160Ser. Two previously reported mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. The present study demonstrates that mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis.

PubMed

de Haas, S; Ghossein-Doha, C; van Kuijk, S M J; van Drongelen, J; Spaanderman, M E A

2017-02-01

To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07-1.19 L), an increase of 45.6% (95% CI, 43.0-48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59-1.02 L), an increase of 32.3% (95% CI, 23.6-41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001). During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptación fisiológica del volumen del plasma materno durante el embarazo: una revisi\\xF3n sistemática y metaanálisis RESUMEN OBJETIVO: Describir el patrón fisiológico de los cambios en el volumen del plasma gestacional en embarazos normales con feto único y compararlo con el patrón en los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal. MÉTODOS: Se realizó un metaanálisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiológicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmático (no embarazada, antes del embarazo o después del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmático a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird. En el metaanálisis se incluyeron treinta estudios con fechas de publicación entre 1934 y 2007. El volumen plasmático aumentó en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuó aumentando en el tercer trimestre con un aumento combinado máximo de 1,13L (IC 95%, 1,7-1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0-48,1%) en embarazos fisiológicas en comparación con el valor de referencia. El aumento del volumen plasmático en los embarazos con hipertensión y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59-1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6-41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiológicos (P <0,0001). Durante el embarazo fisiológico el volumen de plasma aumenta, en promedio, más de 1L, en comparación con el de las no embarazadas. En los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal, el aumento del volumen plasmático en el tercer trimestre es un 13,3% menor que en el embarazo normal. :meta : ,、。 : meta。PubMed(NCBI)EMBASE(Ovid)。(、)。DerSimonianLaird,。 : Meta30,19342007。,。,1.13 L(95% CI,1.07~1.19 L),,45.6%(95% CI,43.0%~48.1%)。0.80 L(95%CI,0.59~1.02 L),32.3%(95% CI,23.6%~41.1%),(P<0.0001)。 : ,,1 L。、,13.3%。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

La inserción en el mercado laboral de los inmigrantes latinos en España y en los Estados Unidos: Diferencias por país de origen y estatus legal

PubMed Central

Connor, Phillip; Massey, Douglas

2013-01-01

Resumen Este artículo compara los resultados económicos entre los inmigrantes latinoamericanos en España y Estados Unidos. Detectamos un efecto de selección por el que la mayoría de los inmigrantes latinoamericanos en España proceden de Sudamérica de un entorno de clases medias, mientras la mayoría de los inmigrantes que van a los Estados Unidos son centroamericanos de clase baja. Este efecto de selección explica las diferencias transnacionales en la probabilidad de empleo, logro ocupacional y salarios obtenidos. A pesar de las diferencias en los orígenes y las características de los latinoamericanos en ambos países, los factores demográficos, humanos y de capital social parecen operar de forma similar en ambos países; y cuando los modelos se estiman separadamente por estatus legal, descubrimos que los efectos se acentúan más entre los inmigrantes irregulares cuando se los compara con los regulares, especialmente en Estados Unidos. PMID:24532857

New Findings on Aromatic Compounds' Degradation and Their Metabolic Pathways, the Biosurfactant Production and Motility of the Halophilic Bacterium Halomonas sp. KHS3.

PubMed

Corti Monzón, Georgina; Nisenbaum, Melina; Herrera Seitz, M Karina; Murialdo, Silvia E

2018-04-24

The study of the aromatic compounds' degrading ability by halophilic bacteria became an interesting research topic, because of the increasing use of halophiles in bioremediation of saline habitats and effluents. In this work, we focused on the study of aromatic compounds' degradation potential of Halomonas sp. KHS3, a moderately halophilic bacterium isolated from hydrocarbon-contaminated seawater of the Mar del Plata harbour. We demonstrated that H. sp. KHS3 is able to grow using different monoaromatic (salicylic acid, benzoic acid, 4-hydroxybenzoic acid, phthalate) and polyaromatic (naphthalene, fluorene, and phenanthrene) substrates. The ability to degrade benzoic acid and 4-hydroxybenzoic acid was analytically corroborated, and Monod kinetic parameters and yield coefficients for degradation were estimated. Strategies that may enhance substrate bioavailability such as surfactant production and chemotactic responses toward aromatic compounds were confirmed. Genomic sequence analysis of this strain allowed us to identify several genes putatively related to the metabolism of aromatic compounds, being the catechol and protocatechuate branches of β-ketoadipate pathway completely represented. These features suggest that the broad-spectrum xenobiotic degrader H. sp. KHS3 could be employed as a useful biotechnological tool for the cleanup of aromatic compounds-polluted saline habitats or effluents.

Compound heterozygous HAX1 mutations in a Swedish patient with severe congenital neutropenia and no neurodevelopmental abnormalities.

PubMed

Carlsson, Göran; Elinder, Göran; Malmgren, Helena; Trebinska, Alicja; Grzybowska, Ewa; Dahl, Niklas; Nordenskjöld, Magnus; Fadeel, Bengt

2009-12-01

Kostmann disease or severe congenital neutropenia (SCN) is an autosomal recessive disorder of neutrophil production. Homozygous HAX1 mutations were recently identified in SCN patients belonging to the original family in northern Sweden described by Kostmann. Moreover, recent studies have suggested an association between neurological dysfunction and HAX1 deficiency. Here we describe a patient with a compound heterozygous HAX1 mutation consisting of a nonsense mutation (c.568C > T, p.Glu190X) and a frame-shift mutation (c.91delG, p.Glu31LysfsX54) resulting in a premature stop codon. The patient has a history of neutropenia and a propensity for infections, but has shown no signs of neurodevelopmental abnormalities.

Genetic analysis of maternal ability in Iberian pigs.

PubMed

Rodriguez, C; Rodrigañez, J; Silio, L

1994-01-12

A practical measure of milk yield of the sow is the weight of the litter at three weeks of age when the piglet growth is entirely dependent on the milking ability of the dam. Genetic parameters of litter size at birth (LS) and litter weight at 21 days (LW21) were estimated using a DFREML procedure from records of 4883 litters (2,049 for LW21) of Iberian breed. Preliminary analysis showed negligible maternal genetic effects. The model for both traits included the fixed effects of farrowing period (86 levels), parity (6) and inbreeding coefficients of dam (Fd) and litter (F(1) ) as co-variables, and three random effects-additive genetic value, permanent environmental effect and residual on both traits. Heritability and repeatability estimates were 0.064 and 0.126 (LS) and 0.163 and 0.270 (LW21) respectively. Estimated genetic and phenotypic correlations were 0.214 and 0.043. The inbreeding depression per 10 % increase of Fd or F(1) was -0.150 or -0.170 in live piglets and -0.983 or -1.023 kg of litter weight. When the model for LW21 included the dam inbreeding and the number of suckling piglets as co-variables, the heritability and repeatability estimates were 0.243 and 0.431 respectively. A complementary analysis was carried out on individual records (weight at 21 days) of 26206 piglets farrowed by 1317 sows. The model included the fixed effects of sex, farrowing period, parity, and the inbreeding coefficients of dam and individual, as co-variables. A total of four random effects were also included: direct and maternal genetic effects, common environmental effects and residual. Estimates of heritability, maternal heritability and common environmental coefficient were, respectively, 0.019, 0.163 and 0.128, reinforcing the evidence of genetic variance for milk producing ability in Iberian sows. The estimated values of inbreeding depression for piglet weight at 21 days were -0.072 and -0.098 kg per 10 % increase in dam or litter inbreeding. ZUSAMMENFASSUNG: Genetische Analyse von Muttereigenschaften iberischer Schweine Ein praktisches Maß für Milchleistung von Sauen ist das Drei-Wochen-Wurfgewicht, das völlig von der Muttermilchleistung abhängt. Genetische Parameter für Geburtswurfgröße (LS) und Geburtswurfgewicht bei 21 Tagen (LW21) wurden mit DFREML von 4883 Würfen (2049 für LW21) geschätzt. Vorläufige Analysen zeigten vernachläßigbare maternale Wirkungen. Das Modell enthält fixe Wirkungen der Wurfperiode (86), Wurffolge (6) und Inzuchtkoeffizienten von Muttersau (Fd) und Wurf (F(1) ) als Ko-variable und dazu drei zufällige Wirkungen: additiv-genetischer Wert, permanenter Umwelteinfluß und der Rest, bei beiden Merkmalen. Heritabilität und Wiederholbarkeit wurden auf 0,064 und 0,126 (LS) und auf 0,163 und 0,270 (LW21) geschätzt. Genetische und phänotypische Korrelationen waren 0,214 bzw. 0,043. Inzuchtdepression pro 10 % für Fd bzw. Fl waren -0,15 bzw. -0,17 bei lebenden Ferkeln und -0,983 bzw. -1,023 Kg in Wurfgewicht. Wenn im Modell für LW21 Mutterinzucht und Zahl saugender Ferkel berücksichtigt wurde, waren die Heritabilitäts- und Wiederholbarkeitsschätzungen 0,243 und 0,431. Eine komplementäre Analyse wurde für Einzelgewichte bei 21 Tagen an 26206 Ferkel von 1317 Sauen durchgeführt. Das Modell enthält festgesetzte Wirkungen von Geschlecht, Wurfperiode, Wurffolge und Inzuchtkoeffizient von Mutter und Ferkel sowie vier zufällige Wirkungen: direkte und maternale Wirkungen, gemeinsame Umweltwirkungen und den Rest. Schätzwerte für Heritabilität, maternale Heritabilität und Wurfumwelt waren 0,019, 0,163 bzw. 0,128, was auf genetische Varianz bei Milchleistung iberischer Sauen hinweist. Die geschätzten Werte für Inzucht-depression für Drei-Wochen-Ferkelgewicht waren -0,072 und -0,098 pro 10% Inzuchtsteigerung von Muttersau und Wurf. RESUMEN: Análisis genético de la aptitud maternal en cerdos ibéricos Una medida práctica de la capacidad lechera de la cerda es el peso de la camada con tres semanas cuando el crecimiento del lechón depende exclusivamente de la producción lechera de la madre. Mediante el procedimiento DFREML se han estimado parámetros genéticos para el tamaño de camada al nacimiento (LS) y peso de la camada a 21 dias (LW21) a partir de 4883 camadas (2049 para LW21) de cerdos Ibéricos. Análisis preliminares mostraron la inexistencia de efectos genéticos maternales significativos sobre ambos caracteres. El modelo ha incluido el efecto fijo de la paridera (86 niveles), orden de parto (6) y los coeficientes de consanguinidad de la madre (Fd) y de la camada (Fl) como covariables, y tres efectos aleatorios: valor genético aditivo, ambiente permanente y residuo. La heredabilidad y repetibilidad estimadas fueron 0,064 y 0,126 (LS) y 0,163 y 0,270 (LW21). Las correlaciones genética y fenotipica fueron 0,214 y 0,043. La depresión consanguinea por 10 % de aumento de Fd o Fl fue -0,150 y -0,170 lechones vivos para LS y -0,983 y - 1,023 kg para LW21. Cuando el modelo para LW21 incluyó como covariables la consanguinidad de la madre y el número de lechones criados, la heredabilidad y repetibilidad estimadas fueron 0,243 y 0,431. Se efectuó un análisis complementario mediante un modelo con efectos maternos de registros de peso a 21 dias de 26206 lechones nacidos de 1317 cerdas. Las estimas de heredabilidad, heredabilidad maternal y coeficiente de ambiente común de camada fueron 0,019, 0,163 y 0,128 respectivamente, reforzando la evidencia de variabilidad genética para la aptitud lechera en cerdas Ibéricas. Los valores de depresión consanguinea estimados para el peso del lechón a 21 dias fueron -0,072 y -0,098 kg por 10 % de aumento de consanguinidad de la madre o del individuo. 1994 Blackwell Verlag GmbH.

Occurrence of the - -(SEA), - -(THAI) and - -(FIL) α-Thalassemia-1 Carriers from a 7-Year Study at Ramathibodi Hospital, Bangkok, Thailand.

PubMed

Pongjantharasatien, Kobkorn; Banyatsuppasin, Wansa; Pounsawat, Sonnarong; Jindadamrongwech, Sumalee

2016-08-01

α-Thalassemia (α-thal) is one of the most common genetic diseases in Thailand. Homozygosity of α-thal-1 (- -/- -) and compound heterozygosity of α-thal-1/α-thal-2 (- -/-α) leads to Hb Bart's (γ4) hydrops fetalis and Hb H (β4) disease, respectively. In order to better control and provide prevention of α-thal disease, the prevalence of α-thal-1 carriers and the types of genotypes in the Thai population should be known. A 7-year retrospective study, employing multiplex gap-polymerase chain reaction (gap-PCR) of 31,632 blood samples from Ramathibodi Hospital, Mahidol University, Bangkok, revealed an α-thal-1 carrier rate of 14.40% with the - -(SEA) (NG_000006.1: g.26264_45564del19301), - -(THAI) (NG_000006.1: g.10664_44164del33501) and - -(FIL) (NG_000006.1: g.11684_43534del31851) genotypes, constituting frequencies of 14.21, 0.18 and 0.01%, respectively. Although the - -(FIL) genotype is rare in the Thailand, its detection should be included in future α-thal screening programs.

Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India.

PubMed

Warren, John F; Aldave, Anthony J; Srinivasan, M; Thonar, Eugene J; Kumar, Abha B; Cevallos, Vicky; Whitcher, John P; Margolis, Todd P

2003-11-01

To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India. An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

PubMed

Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

2016-08-01

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

PubMed Central

Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

2016-01-01

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment. PMID:27035618

Both XPD alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients

PubMed Central

Ueda, Takahiro; Compe, Emmanuel; Catez, Philippe; Kraemer, Kenneth H.

2009-01-01

Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP). Many XP patients are compound heterozygotes with a “causative” XPD point mutation R683W and different second mutant alleles, considered “null alleles.” However, there is marked clinical heterogeneity (including presence or absence of skin cancers or neurological degeneration) in these XPD/R683W patients, thus suggesting a contribution of the second allele. Here, we report XP patients carrying XPD/R683W and a second XPD allele either XPD/Q452X, /I455del, or /199insPP. We performed a systematic study of the effect of these XPD mutations on several enzymatic functions of TFIIH and found that each mutation exhibited unique biochemical properties. Although all the mutations inhibited the nucleotide excision repair (NER) by disturbing the XPD helicase function, each of them disrupted specific molecular steps during transcription: XPD/Q452X hindered the transactivation process, XPD/I455del disturbed RNA polymerase II phosphorylation, and XPD/199insPP inhibited kinase activity of the cdk7 subunit of TFIIH. The broad range and severity of clinical features in XP patients arise from a broad set of deficiencies in NER and transcription that result from the combination of mutations found on both XPD alleles. PMID:19934020

Inhibitory effect of tocotrienol on eukaryotic DNA polymerase {lambda} and angiogenesis

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

Mizushina, Yoshiyuki; Nakagawa, Kiyotaka; Shibata, Akira

2006-01-20

Tocotrienols, vitamin E compounds that have an unsaturated side chain with three double bonds, selectively inhibited the activity of mammalian DNA polymerase {lambda} (pol {lambda}) in vitro. These compounds did not influence the activities of replicative pols such as {alpha}, {delta}, and {epsilon}, or even the activity of pol {beta} which is thought to have a very similar three-dimensional structure to the pol {beta}-like region of pol {lambda}. Since {delta}-tocotrienol had the strongest inhibitory effect among the four ({alpha}- to {delta}-) tocotrienols, the isomer's structure might be an important factor in the inhibition of pol {lambda}. The inhibitory effect ofmore » {delta}-tocotrienol on both intact pol {lambda} (residues 1-575) and a truncated pol {lambda} lacking the N-terminal BRCA1 C-terminus (BRCT) domain (residues 133-575, del-1 pol {lambda}) was dose-dependent, with 50% inhibition observed at a concentration of 18.4 and 90.1 {mu}M, respectively. However, del-2 pol {lambda} (residues 245-575) containing the C-terminal pol {beta}-like region was unaffected. Tocotrienols also inhibited the proliferation of and formation of tubes by bovine aortic endothelial cells, with {delta}-tocotrienol having the greatest effect. These results indicated that tocotrienols targeted both pol {lambda} and angiogenesis as anti-cancer agents. The relationship between the inhibition of pol {lambda} and anti-angiogenesis by {delta}-tocotrienol was discussed.« less

Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines.

PubMed

Woode, Denzel R; Aiyer, Harini S; Sie, Nicole; Zwart, Alan L; Li, Liya; Seeram, Navindra P; Clarke, Robert

2012-01-01

Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1-100 μg/mL) or with a sub-lethal dose of ICI ( 1). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses.

Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines

PubMed Central

Woode, Denzel R.; Aiyer, Harini S.; Sie, Nicole; Zwart, Alan L.; Li, Liya; Seeram, Navindra P.; Clarke, Robert

2012-01-01

Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1–100 μg/mL) or with a sub-lethal dose of ICI ( 1). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses. PMID:23346406

Use of black vulture (Coragyps atratus) in complementary and alternative therapies for cancer in Colombia: A qualitative study

PubMed Central

2012-01-01

Background Although Coragyps atratus has been used as a traditional therapy for patients with cancer, the scientific literature does not contain enough information on how this therapy is used or the mechanisms that explain this therapeutic practice. Objectives To understand the methods of use and the reasons given by patients and caregivers for the use of Coragyps atratus in cancer treatment. Methods This study used a qualitative design based on twenty in-depth interviews of patients with cancer or caregivers of patients with the disease. The analysis of the text was based on an inductive thematic approach. Results Resistance to disease and immune enhancement are properties attributed to Coragyps atratus when used for cancer treatment. The most recommended method of use is fresh blood ingestion, and the associated mechanism of action is transfer of immune factors to the individual who consumes it. Conclusions Use of Coragyps atratus as a treatment for cancer is a popular alternative therapy in Colombia. More studies are needed to understand the clinical effects of this intervention in cancer patients. Spanish abstract Introducción Aunque Coragyps atratus se usa tradicionalmente como terapia para pacientes con cáncer, no existe suficiente información en la literatura científica sobre su forma de utilización ni sobre los mecanismos explicativos que subyacen a esta práctica terapéutica. Objetivos Conocer métodos de utilización y mecanismos explicativos dados por los pacientes y cuidadores de pacientes sobre el uso de Coragyps atratus en el tratamiento del cáncer. Materiales y métodos Diseño cualitativo basado en veinte entrevistas en profundidad de pacientes con cáncer o cuidadores de pacientes con esta enfermedad. Análisis de texto basado en enfoque temático inductivo. Resultados Al Coragyps atratus se le atribuyen propiedades de resistencia y fortalecimiento del sistema inmune de personas enfermas de cáncer. La forma de utilización mas común es la ingesta de la sangre fresca y el mecanismo de acción asociado es la transferencia de defensas a quien lo consume. Conclusiones La utilización del Coragyps atratus como tratamiento para el cáncer es una terapia alternativa usada popularmente en Colombia. El uso de este animal debe estudiarse más a fondo para conocer los efectos clínicos en los pacientes con cáncer. PMID:22651097

Compound Libraries: Recent Advances and Their Applications in Drug Discovery.

PubMed

Gong, Zhen; Hu, Guoping; Li, Qiang; Liu, Zhiguo; Wang, Fei; Zhang, Xuejin; Xiong, Jian; Li, Peng; Xu, Yan; Ma, Rujian; Chen, Shuhui; Li, Jian

2017-01-01

Hit identification is the starting point of small-molecule drug discovery and is therefore very important to the pharmaceutical industry. One of the most important approaches to identify a new hit is to screen a compound library using an in vitro assay. High-throughput screening has made great contributions to drug discovery since the 1990s but requires expensive equipment and facilities, and its success depends on the size of the compound library. Recent progress in the development of compound libraries has provided more efficient ways to identify new hits for novel drug targets, thereby helping to promote the development of the pharmaceutical industry, especially for firstin- class drugs. A multistage and systematic research of articles published between 1986 and 2017 has been performed, which was organized into 5 sections and discussed in detail. In this review, the sources and classification of compound libraries are summarized. The progress made in combinatorial libraries and DNA-encoded libraries is reviewed. Library design methods, especially for focused libraries, are introduced in detail. In the final part, the status of the compound libraries at WuXi is reported. The progress related to compound libraries, especially drug template libraries, DELs, and focused libraries, will help to identify better hits for novel drug targets and promote the development of the pharmaceutical industry. Moreover, these libraries can facilitate hit identification, which benefits most research organizations, including academics and small companies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Global Analysis of Anthropogenic Debris Ingestion by Sea Turtles

PubMed Central

Schuyler, Qamar; Hardesty, Britta Denise; Wilcox, Chris; Townsend, Kathy

2014-01-01

Ingestion of marine debris can have lethal and sublethal effects on sea turtles and other wildlife. Although researchers have reported on ingestion of anthropogenic debris by marine turtles and implied incidences of debris ingestion have increased over time, there has not been a global synthesis of the phenomenon since 1985. Thus, we analyzed 37 studies published from 1985 to 2012 that report on data collected from before 1900 through 2011. Specifically, we investigated whether ingestion prevalence has changed over time, what types of debris are most commonly ingested, the geographic distribution of debris ingestion by marine turtles relative to global debris distribution, and which species and life-history stages are most likely to ingest debris. The probability of green (Chelonia mydas) and leatherback turtles (Dermochelys coriacea) ingesting debris increased significantly over time, and plastic was the most commonly ingested debris. Turtles in nearly all regions studied ingest debris, but the probability of ingestion was not related to modeled debris densities. Furthermore, smaller, oceanic-stage turtles were more likely to ingest debris than coastal foragers, whereas carnivorous species were less likely to ingest debris than herbivores or gelatinovores. Our results indicate oceanic leatherback turtles and green turtles are at the greatest risk of both lethal and sublethal effects from ingested marine debris. To reduce this risk, anthropogenic debris must be managed at a global level. Análisis Global de la Ingesta de Residuos Antropogénicos por Tortugas Marinas La ingesta de residuos marinos puede tener efectos letales y subletales sobre las tortugas marinas y otros animales. Aunque hay investigadores que han reportado la ingesta de residuos antropogénicos por tortugas marinas y la incidencia de la ingesta de residuos ha incrementado con el tiempo, no ha habido una síntesis global del fenómeno desde 1985. Por esto analizamos 37 estudios publicados, desde 1985 hasta 2012, que reportan datos colectados desde antes de 1900 y a lo largo del 2011. Investigamos específicamente si el predominio de la ingesta ha cambiado con el tiempo, qué tipos de residuos se ingieren comúnmente, la distribución geográfica de la ingesta de residuos por tortugas marinas en relación a la distribución global de residuos y cuáles especies y etapas de vida tienen más probabilidad de ingerir residuos. La probabilidad de que las tortugas verdes (Chelonia mydas) y laúd (Dermochelys coriacea) ingieran escombros incrementa significativamente con el tiempo; plástico fue el residuo que más se ingirió. Las tortugas en casi todas las regiones estudiadas ingieren residuos, pero la probabilidad de ingesta no estuvo relacionada con las densidades modeladas de residuos. Además de esto, tortugas más pequeñas, en etapa oceánica de vida, tuvieron una mayor probabilidad de ingerir residuos que las tortugas forrajeras terrestres, mientras que las especies carnívoras tuvieron menos probabilidad de ingerir residuos que las herbívoras o las gelatinívoras. Nuestros resultados indican que las tortugas verdes y laúd tienen el mayor riesgo de efectos letales y subletales de la ingesta de residuos marinos. Para reducir el riesgo, los residuos antropogénicos deben manejarse en un nivel global. PMID:23914794

Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

PubMed Central

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

2013-01-01

The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families. PMID:24058621

Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm.

PubMed

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

2013-01-01

The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.

Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis.

PubMed

Bittencourt, Paulo Lisboa; Marin, Maria Lúcia Carnevale; Couto, Cláudia Alves; Cançado, Eduardo Luiz Rachid; Carrilho, Flair José; Goldberg, Anna Carla

2009-01-01

Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.

The Implications of Orthographic Intraference for the Teaching and Description of ESL: The Educated Nigerian English Examples (Implicaciones de la Intraferencia Ortográfica para la Enseñanza y Descripción del Inglés como Segunda Lengua: Ejemplos Inglés Nigeriano Formal)

ERIC Educational Resources Information Center

Ekundayo, Omowumi Steve Bode

2015-01-01

This paper examines orthographic intraference and its implications for teaching and describing English as a second language (ESL). Orthographic intraference is used here to denote instances of single word spelling, acronyms, mix up of homophones, homonyms and compound word spelling arising not from interference but from orthographic rules and…

Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

PubMed

Bosch, Daniëlle G M; Boonstra, F Nienke; Kinoshita, Taroh; Jhangiani, Shalini; de Ligt, Joep; Cremers, Frans P M; Lupski, James R; Murakami, Yoshiko; de Vries, Bert B A

2015-12-01

Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency and revealed compound heterozygous variants in PGAP1, c.274_276del (p.(Pro92del)) and c.921_925del (p.(Lys308Asnfs*25)). Subsequently, PGAP1-deficient Chinese hamster ovary (CHO)-cell lines were transfected with either mutant or wild-type constructs and their sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment was measured. The mutant constructs could not rescue the PGAP1-deficient CHO cell lines resistance to PI-PLC treatment. In addition, lymphoblastoid cell lines (LCLs) of the affected individual showed no sensitivity to PI-PLC treatment, whereas the LCLs of the heterozygous carrier parents were partially resistant. In conclusion, we report novel PGAP1 variants in a boy with CVI and ID and a proven functional loss of PGAP1 and show, to our knowledge, for the first time this genetic association with CVI.

[In Process Citation].

PubMed

Alarcón Hormazábal, Manuel; Delgado Floody, Pedro; Castillo Mariqueo, Lidia; Thuiller Lepelegy, Nicole; Bórquez Becerra, Pablo; Sepúlveda Mancilla, Carlos; Rebolledo Quezada, Sara

2016-03-25

Introducción: existe una alta prevalencia de sedentarismo, sobrepeso y obesidad en jóvenes universitarios. Objetivo: el propósito del estudio fue determinar los efectos de un programa de entrenamiento intervalado de alta intensidad (HIIT) sobre el perfil antropométrico, glicemia basal y VO 2 máx (consumo máximo de oxígeno) de jóvenes sedentarios con malnutrición por exceso. Material y métodos: 6 mujeres y 2 hombres (2 obesos y 6 con sobrepeso) se sometieron a un programa de entrenamiento de alta intensidad de 8 semanas de duración (3 sesiones/semana). Se evaluó en ayuno y posterior a 72 horas de la última intervención; peso, índice de masa corporal (IMC), contorno de cintura (CC), perímetro de cadera y glicemia de basal. El VO 2 máx fue evaluado en condiciones normales previo a la primera sesión. Resultados: las variables de estudio no presentaron cambios significativos (p > 0,05), pero reportaron disminuciones porcentuales. El peso disminuyó un 0,18%, el IMC un 0,27%, el CC 2,67%, el perímetro de cadera un 1,15%, y el VO 2 máx un 0,48%. La glicemia basal presentó la mayor disminución, pasó de 95,13 ± 23,91 a 89,88 ± 12,45 mg/dl (5,52%), estabilizando y mejorando sus niveles en cada uno de los participantes. Conclusiones: el programa de entrenamiento intervalado de alta intensidad fue factible de realizar sin resultados adversos para la salud de los participantes, la glicemia basal mostró la mayor variación, estabilizando sus valores en los participantes, lo que es un indicador positivo dentro del programa. Es necesario seguir investigando sobre esta metodología HIIT y aumentar los tiempos de estudio para ver los cambios que se pueden producir en distintos parámetros metabólicos, antropométricos y físicos en población con malnutrición por exceso.

[Not Available].

PubMed

MIján de la Torre, Alberto

2016-06-03

El síndrome de caquexia cancerosa es responsable de la muerte de un número significativo de pacientes con cáncer. Se caracteriza por la presencia de una ingesta reducida, con inflamación sistémica y un metabolismo alterado. Los enfermos presentan característicamente una progresiva pérdida de peso y de masa muscular, junto a deterioro funcional. La pérdida muscular se debe a la combinación de reducción de la síntesis proteica con aumento de su degradación. Ello conduce tanto a un acortamiento como a una reducción en el área de la fibra muscular. Asimismo, existen datos que apoyan que selectivamente algunos de los tipos de fibra muscular se ven más afectados. Es necesario definir bien los valores de corte de sarcopenia para diagnosticar la pérdida muscular y existen diferentes métodos. El sistema de la ubiquitina-proteasoma parece desempeñar un papel predominante en la degradación de la proteína miofibrilar. La tendencia a perder masa muscular en los pacientes con caquexia cancerosa parece estar asociada a la activación de señales catabólicas por citoquinas proinflamatorias, así como por productos tumorales del tipo factor inductor de proteólisis. En referencia a los factores pronósticos, el riesgo de muerte está bien documentado en pacientes con sarcopenia y, especialmente, en aquellos con obesidad asociada a la sarcopenia. Asimismo, se ha establecido una relación directa entre la pérdida intensa de masa muscular y la supervivencia en pacientes con diferentes tipos de tumores del tipo de cáncer de páncreas, pulmón, tracto biliar o cáncer colorrectal. Respecto de la terapia en el síndrome de caquexia cancerosa, es factible que requiera tratamiento con varios grupos combinados que incluyan, junto al soporte nutricional, fármacos orexígenos, con efecto anabólico y antinflamatorio, asociados a intervenciones que estimulen el ejercicio físico.

Combined effects of climate change and bank stabilization on shallow water habitats of chinook salmon.

PubMed

Jorgensen, Jeffrey C; McClure, Michelle M; Sheer, Mindi B; Munn, Nancy L

2013-12-01

Significant challenges remain in the ability to estimate habitat change under the combined effects of natural variability, climate change, and human activity. We examined anticipated effects on shallow water over low-sloped beaches to these combined effects in the lower Willamette River, Oregon, an area highly altered by development. A proposal to stabilize some shoreline with large rocks (riprap) would alter shallow water areas, an important habitat for threatened Chinook salmon (Oncorhynchus tshawytscha), and would be subject to U.S. Endangered Species Act-mandated oversight. In the mainstem, subyearling Chinook salmon appear to preferentially occupy these areas, which fluctuate with river stages. We estimated effects with a geospatial model and projections of future river flows. Recent (1999-2009) median river stages during peak subyearling occupancy (April-June) maximized beach shallow water area in the lower mainstem. Upstream shallow water area was maximized at lower river stages than have occurred recently. Higher river stages in April-June, resulting from increased flows predicted for the 2080s, decreased beach shallow water area 17-32%. On the basis of projected 2080s flows, more than 15% of beach shallow water area was displaced by the riprap. Beach shallow water area lost to riprap represented up to 1.6% of the total from the mouth to 12.9 km upstream. Reductions in shallow water area could restrict salmon feeding, resting, and refuge from predators and potentially reduce opportunities for the expression of the full range of life-history strategies. Although climate change analyses provided useful information, detailed analyses are prohibitive at the project scale for the multitude of small projects reviewed annually. The benefits of our approach to resource managers include a wider geographic context for reviewing similar small projects in concert with climate change, an approach to analyze cumulative effects of similar actions, and estimation of the actions' long-term effects. Efectos Combinados del Cambio Climático y la Estabilización de Bordes de Ríos Hábitats de Aguas Poco Profundas del Salmón Chinook. Conservation Biology © 2013 Society for Conservation Biology No claim to original US government works.

Efficacy Outcome Measures for Clinical Trials of USH2A caused by the Common c.2299delG Mutation.

PubMed

Calzetti, Giacomo; Levy, Richard A; Cideciyan, Artur V; Garafalo, Alexandra V; Roman, Alejandro J; Sumaroka, Alexander; Charng, Jason; Heon, Elise; Jacobson, Samuel G

2018-06-25

To determine the change in vision and retinal structure in patients with the common c.2299delG mutation in the USH2A gene in anticipation of clinical trials of therapy. Retrospective observational case series. Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG mutation in USH2A, were studied with visual acuity, kinetic perimetry, dark- and light-adapted two-color static perimetry, optical coherence tomography (OCT) and autofluorescence (AF) imaging. Serial data were available for at least half of the patients depending on the parameter analyzed. The kinetics of disease progression in this specific molecular form of USH2A differed between the measured parameters. Visual acuity could remain normal for decades. Kinetic and light-adapted static perimetry across the entire visual field had similar rates of decline that were slower than those of rod-based perimetry. Horizontal OCT scans through the macula showed that IS/OS line width had a similar rate of constriction as co-localized AF imaging and cone-based light-adapted sensitivity extent. The rate of constriction of rod-based sensitivity extent across this same region was twice as rapid as that of cones. In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the cells that express disease early and more aggressively than cones. Rod-based vision measurements in central or extracentral-peripheral retinal regions warrant monitoring in order to complete a clinical trial in a timely manner. Copyright © 2018. Published by Elsevier Inc.

Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of Leigh syndrome.

PubMed

Cameron, Jessie M; MacKay, Nevena; Feigenbaum, Annette; Tarnopolsky, Mark; Blaser, Susan; Robinson, Brian H; Schulze, Andreas

2015-09-01

Two siblings with hypertrophic cardiomyopathy and brain atrophy were diagnosed with Complex I deficiency based on low enzyme activity in muscle and high lactate/pyruvate ratio in fibroblasts. Whole exome sequencing results of fibroblast gDNA from one sibling was narrowed down to 190 SNPs or In/Dels in 185 candidate genes by selecting non-synonymous coding sequence base pair changes that were not present in the SNP database. Two compound heterozygous mutations were identified in both siblings in NDUFV2, encoding the 24 kDa subunit of Complex I. The intronic mutation (c.IVS2 + 1delGTAA) is disease causing and has been reported before. The other mutation is novel (c.669_670insG, p.Ser224Valfs*3) and predicted to cause a pathogenic frameshift in the protein. Subsequent investigation of 10 probands with complex I deficiency from different families revealed homozygosity for the intronic c.IVS2 + 1delGTAA mutation in a second, consanguineous family. In this family three of five siblings were affected. Interestingly, they presented with Leigh syndrome but no cardiac involvement. The same genotype had been reported previously in a two families but presenting with hypertrophic cardiomyopathy, trunk hypotonia and encephalopathy. We have identified NDUFV2 mutations in two families with Complex I deficiency, including a novel mutation. The diagnosis of Leigh syndrome expands the clinical phenotypes associated with the c.IVS2 + 1delGTAA mutation in this gene. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Biomarker responses and contamination levels in the clam Ruditapes philippinarum for biomonitoring the Lagoon of Venice (Italy).

PubMed

Matozzo, Valerio; Binelli, Andrea; Parolini, Marco; Locatello, Lisa; Marin, Maria Gabriella

2010-03-01

A multibiomarker approach was used to assess effects of environmental contaminants in the clam Ruditapes philippinarum from the Lagoon of Venice. Bivalves were collected in 8 sites of the Lagoon (Campalto, Marghera, Palude del Monte, Valle di Brenta, Cà Roman, San Servolo, Fusina and Canale Dese), differently influenced by both anthropogenic impact and natural conditions. The following biomarkers were chosen: total haemocyte count and lysozyme activity in cell-free haemolymph as immunomarkers, acetylcholinesterase activity in gills as a biomarker of exposure to neurotoxic compounds, vitellogenin-like protein levels in both digestive gland and cell-free haemolymph as a biomarker of exposure to estrogenic compounds, and survival-in-air widely used to evaluate general stress conditions in clams. In addition, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its breakdown products (DDE, DDD), hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) were measured in clams. Results demonstrated that the integrated approach between biomarkers and chemical analyses in R. philippinarum is a useful tool in biomonitoring the Lagoon of Venice. The biomarker responses suggested quite similar contamination levels in the entire Lagoon, although the relative impact of differing classes of pollutants changed among sites according to potential sources, as chemical analyses demonstrated. Overall, among the sampling sites investigated, Palude del Monte can represent an environmental risk area, bearing in mind its peculiar use for clam culture.

Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation.

PubMed

Clancy, J P; Rowe, Steven M; Accurso, Frank J; Aitken, Moira L; Amin, Raouf S; Ashlock, Melissa A; Ballmann, Manfred; Boyle, Michael P; Bronsveld, Inez; Campbell, Preston W; De Boeck, Kris; Donaldson, Scott H; Dorkin, Henry L; Dunitz, Jordan M; Durie, Peter R; Jain, Manu; Leonard, Anissa; McCoy, Karen S; Moss, Richard B; Pilewski, Joseph M; Rosenbluth, Daniel B; Rubenstein, Ronald C; Schechter, Michael S; Botfield, Martyn; Ordoñez, Claudia L; Spencer-Green, George T; Vernillet, Laurent; Wisseh, Steve; Yen, Karl; Konstan, Michael W

2012-01-01

VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional F508del-CFTR in vitro. A randomised, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis (n=89) who were homozygous for the F508del-CFTR mutation. Subjects were randomised to one of four VX-809 28 day dose groups (25, 50, 100 and 200 mg) or matching placebo. The type and incidence of adverse events were similar among VX-809- and placebo-treated subjects. Respiratory events were the most commonly reported and led to discontinuation by one subject in each active treatment arm. Pharmacokinetic data supported a once-daily oral dosing regimen. Pharmacodynamic data suggested that VX-809 improved CFTR function in at least one organ (sweat gland). VX-809 reduced elevated sweat chloride values in a dose-dependent manner (p=0.0013) that was statistically significant in the 100 and 200 mg dose groups. There was no statistically significant improvement in CFTR function in the nasal epithelium as measured by nasal potential difference, nor were there statistically significant changes in lung function or patient-reported outcomes. No maturation of immature F508del-CFTR was detected in the subgroup that provided rectal biopsy specimens. In this study, VX-809 had a similar adverse event profile to placebo for 28 days in F508del-CFTR homozygous patients, and demonstrated biological activity with positive impact on CFTR function in the sweat gland. Additional data are needed to determine how improvements detected in CFTR function secondary to VX-809 in the sweat gland relate to those measurable in the respiratory tract and to long-term measures of clinical benefit. NCT00865904.

Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines

PubMed Central

2013-01-01

Background Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR. Most of these correctors do not act directly as ligands of CFTR, but indirectly on other pathways to promote folding and correction. We hypothesize that these proteostasis regulators may also correct other protein trafficking diseases. Methods To test our hypothesis, we used stable cell lines or transient transfection to express 2 well-studied trafficking disease mutations in each of 3 different proteins: the arginine-vasopressin receptor 2 (AVPR2, also known as V2R), the human ether-a-go-go-related gene (KCNH2, also known as hERG), and finally the sulfonylurea receptor 1 (ABCC8, also known as SUR1). We treated cells expressing these mutant proteins with 9 structurally diverse F508del-CFTR correctors that function through different cellular mechanisms and assessed whether correction occurred via immunoblotting and functional assays. Results were deemed significantly different from controls by a one-way ANOVA (p < 0.05). Results Here we show that F508del-CFTR correctors RDR1, KM60 and KM57 also correct some mutant alleles of other protein trafficking diseases. We also show that one corrector, the cardiac glycoside ouabain, was found to alter the glycosylation of all mutant alleles tested. Conclusions Correctors of F508del-CFTR trafficking might have broader applications to other protein trafficking diseases. PMID:23316740

Partial deletion of the AGXT gene (EX1_EX7del): A new genotype in hyperoxaluria type 1.

PubMed

Nogueira, P K; Vuong, T S; Bouton, O; Maillard, A; Marchand, M; Rolland, M O; Cochat, P; Bozon, D

2000-04-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal (2q37.3) recessive metabolic disease caused by a deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate amino transferase. Molecular heterogeneity is important in PH1 as most of the patients (if the parents are unrelated) are compound heterozygotes for rare mutations. We describe the first large deletion in the AGXT gene, removing exons 1 to 7 (EX1_EX7del) that was responsible for one case of severe PH1. This 10 kb deletion was identified by Southern blotting of genomic DNA digested by Xba I and hybridized with different exonic probes. Both parents (from Turkey) are first cousin and carry the deletion. It is of note that the presently reported patient did not exhibit any AGT catalytic activity and even so, he progressed towards end-stage renal disease only at 19 years old. Copyright 2000 Wiley-Liss, Inc.

Contaminación por mercurio de leche materna de madres lactantes de municipios de Antioquia con explotación minera de oro.

PubMed

Molina, Carlos Federico; Arango, Catalina María; Sepúlveda, Hernán

2018-05-01

Introducción. La leche materna es esencial para el desarrollo del ser humano, pero puede contener sustancias tóxicas provenientes de la contaminación ambiental, especialmente en las áreas mineras.Objetivo. Determinar la prevalencia de la contaminación con mercurio de la leche materna de mujeres lactantes residentes en los municipios con explotación minera de oro.Materiales y métodos. Se hizo un estudio transversal de 150 madres lactantes de cuatro municipios mineros de Antioquia (El Bagre, Segovia, Remedios y Zaragoza), a quienes se les hizo una encuesta sobre factores sociodemográficos, ocupacionales y ambientales relacionados con el mercurio, y se les tomaron muestras de leche materna, de orina y de cabello. Se calculó el promedio de la concentración de mercurio y las prevalencias municipales de contaminación.Resultados. El promedio de la concentración de mercurio en la leche materna fue de 2,5 (± desviación estándar 9,2) μg/L. La prevalencia de muestras de leche materna con niveles altos de mercurio fue de 11,7 %.Conclusión. En este estudio se evidencia un grave problema en las regiones mineras auríferas de Antioquia por el efecto de la contaminación con mercurio en sectores de la población más vulnerable.

Análisis del futuro marco de referencia internacional

NASA Astrophysics Data System (ADS)

Cionco, G. R.; Arias, E. F.

La técnica de interferometría de muy larga línea de base (VLBI) se aplica hoy a la astrometría para el cálculo de posiciones precisas de radiofuentes extragalácticas. Por tratarse de objetos lejanos, sus movimientos propios aparentes pueden considerarse nulos; esta propiedad hace que los catálogos de radiofuentes extragalácticas VLBI constituyan la mejor materialización de un sistema de referencia celeste inercial definido cinemáticamente. La Unión Astronómica Internacional (IAU) recomendó la adopción de un nuevo sistema de referencia celeste internacional materializado por las coordenadas ecuatoriales de objetos extragalácticos observados con le técnica VLBI. Para superar la precisión astrométrica actual es necesaria una mejora en la modelización de aquellos fenómenos que pueden introducir desviaciones sistemáticas en el marco de referencia celeste. El objetivo de este trabajo es poner de manifiesto las sistematicidades presentes en los distintos marcos de referencia elaborados con el próposito de materializar el nuevo sistema de referencia celeste de la IAU. Para la comparación de los distintos marcos de referencia se propone un modelo de tres rotaciones diferenciales más un término lineal que procura absorber los efectos sistemáticos presentes en las coordenadas. Se analiza igualmente la estabilidad de la solución cuando se utilizan distintos conjuntos de objetos de definición.

Capture-zone design in an aquifer influenced by cyclic fluctuations in hydraulic gradients

NASA Astrophysics Data System (ADS)

Zawadzki, Willy; Chorley, Don; Patrick, Guy

2002-10-01

Design of a groundwater pumping and treatment system for a wood-treatment facility adjacent to the tidally influenced Fraser River estuary required the development of methodologies to account for cyclic variations in hydraulic gradients. Design of such systems must consider the effects of these cyclic fluctuations on the capture of dissolved-phase contaminants. When the period of the cyclic fluctuation is much less than the travel time of the dissolved contaminant from the source to the discharge point, the hydraulic-gradient variations resulting from these cycles can be ignored. Capture zones are then designed based on the average hydraulic gradient determined using filter techniques on continuous groundwater-level measurements. When the period of cyclic fluctuation in hydraulic gradient is near to or greater than the contaminant travel time, the resulting hydraulic-gradient variations cannot be ignored. In these instances, procedures are developed to account for these fluctuations in the capture-zone design. These include proper characterization of the groundwater regime, assessment of the average travel time and period of the cyclic fluctuations, and numerical techniques which allow accounting for the cyclic fluctuations in the design of the capture zone. Résumé. L'étude d'un système de pompage et de traitement de l'eau souterraine d'une usine de traitement du bois proche de l'estuaire de la rivière Fraser, influencé par les marées, a nécessité la mise au point de méthodologies pour prendre en compte les variations cycliques de gradients hydrauliques. L'étude de tels systèmes doit considérer les effets de ces variations cycliques sur l'extraction des contaminants en phase dissoute. Lorsque la période des variations cycliques est très inférieure au temps de parcours du contaminant dissous entre la source et le point d'émergence, les variations du gradient hydraulique résultant de ces cycles peuvent être ignorées. Les zones d'extraction sont alors réalisées sur la base du gradient hydraulique moyen déterminé au moyen de techniques de filtrage sur des mesures continues de la piézométrie. Lorsque la période de la fluctuation cyclique dans le gradient hydraulique est proche de ou supérieure au temps de parcours du contaminant, les variations résultantes de gradient hydraulique ne peuvent plus être ignorées. Dans ces cas-là, des procédures ont été mises au point pour prendre en compte ces fluctuations dans la conception de la zone d'extraction. Celles-ci prennent en considération la caractérisation propre du régime de la nappe, l'évaluation du temps de parcours moyen et de la période des fluctuations cycliques, et des techniques numériques qui permettent de considérer les fluctuations cycliques dans la conception de la zone d'extraction. Resumen. El diseño de un sistema de bombeo y tratamiento de aguas subterráneas para una instalación de manufactura de madera que está próxima al estuario del río Fraser, sometido a la influencia de las mareas, ha requerido el desarrollo de metodologías para tener en cuenta las variaciones cíclicas de los gradientes hidráulicos. El diseño de tales sistemas debe considerar los efectos de las fluctuaciones cíclicas en la captura de contaminantes en fase disuelta. Cuando el período de la fluctuación cíclica es mucho menor que el tiempo de tránsito del contaminante disuelto entre el punto de entrada y el de descarga, se puede ignorar las variaciones del gradiente hidráulico provocadas por dichos ciclos. Las zonas de captura se diseñan entonces en función del gradiente hidráulico promedio, que se determina mediante técnicas de filtrado de medidas continuas del nivel piezométrico. Cuando el período de la fluctuación cíclica del gradiente hidráulico es comparable o mayor que el tiempo de tránsito del contaminante, no puede ignorarse las variaciones resultantes en el gradiente hidráulico. En ese caso, se tiene que desarrollar procedimientos para contar con las fluctuaciones en el diseño de las zonas de captura. Ello implica una adecuada caracterización del régimen de las aguas subterráneas, el establecimiento del tiempo de tránsito y del período de las fluctuaciones cíclicas, y el uso de técnicas numéricas que permitan incluirlas en el diseño de la zona de captura.

¿Qué es un repelente de insectos?

EPA Pesticide Factsheets

Según la ley de pesticidas, estos productos son cualquier sustancia o mezcla de sustancias destinadas a lo siguiente: prevenir; eliminar; repeler; mitigar cualquier peste. (Mitigar significa reducir el efecto de algo).

Evolución de planetas gigantes y posibilidades de su detección directa

NASA Astrophysics Data System (ADS)

Brunini, A.; Benvenuto, O. G.

Desde la reciente detección de planetas gigantes orbitando estrellas cercanas de tipo solar por medio de efecto Doppler, uno de los principales problemas, en cuanto al estudio de los sistemas planetarios extrasolares, se refiere a la posibilidad de obtener evidencia directa de su existencia. Esto parece ser factible gracias a que en un futuro cercano entrarán en operación algunos telescopios especialmente adecuados a estos propósitos. Por tal motivo, hemos comenzado desde hace un tiempo un esfuerzo en cuanto al estudio de la evolución planetaria. A tales efectos hemos adaptado el código de evolución estelar de nuestro Observatorio al caso planetario. Las principales diferencias entre el caso estelar y el planetario se encuentran en la ecuación de estado. A tales fines hemos incluído la reciente ecuación de estado de Saumon, Chabrier y Van Horn, las opacidades radiativas de Guillot et al., procesos de quema de Deuterio, etc. También se ha considerado la posible existencia de fases de hielo y roca en el interior planetario. Por el momento hemos despreciado los efectos de la rotación planetaria. Con este código hemos computado la evolución de planetas con masas desde 10 hasta 0.3 masas de Júpiter. Utilizando nuestros resultados numéricos discutimos la detectabilidad de estos objetos en condiciones realistas.

N/Z effect on reaction mechanisms cross sections in the 78 Kr +40 Ca and 86 Kr +48 Ca collisions at 10 AMeV

NASA Astrophysics Data System (ADS)

Gnoffo, B.; Pirrone, S.; Politi, G.; La Commara, M.; Wieleczko, J. P.; De Filippo, E.; Russotto, P.; Trimarchi, M.; Vigilante, M.; Ademard, G.; Auditore, L.; Beck, C.; Bercenau, I.; Bonnet, E.; Borderie, B.; Cardella, G.; Chibihi, A.; Colonna, M.; Dell'Aquila, D.; De Luca, S.; D'Onofrio, A.; Frankland, J. D.; Lanzalone, G.; Lautesse, P.; Lebhertz, D.; Le Neidre, N.; Lombardo, I.; Martorana, N. S.; Mazurek, K.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Piasecki, E.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Spadaccini, G.; Trifirò, A.; Verde, G.

2017-06-01

Nuclear reactions between medium-mass nuclei at low energy are characterized by the competition between binary and evaporation process in the compound nucleus de-excitation. A study of the influence of the neutron richness of the entrance channel on the decay paths of the compound nuclei formed in the 78 Kr +40 Ca and 86 Kr +48 Ca at 10 MeV/A is presented. The experiment has been performed at Laboratori Nazionali del Sud by using the CHIMERA 4π multidetector for charged particles. The Kinematical characteristics of the two reactions support the conclusion of a production via long lived system. Besides the results relative to the n-poor system are compared to those obtained at GANIL, performed at 5.5 AMeV, in order to study the energy influence.

Mating opportunities in Sangalopsis veliterna females: Costs and benefits

PubMed Central

Hernández Duran, Linda C.; Fajardo Medina, Gonzalo E.; Fuentes Quinter, Luz S.; Martin, Oliver

2014-01-01

Abstract In nature, females of several animal taxa exhibit considerable variation in their mating system, and this variation involves different balances of costs (e.g., energetic, reproductive) and benefits (e.g., increased net reproductive rate of the female, increased longevity). Many studies have focused on discovering the potential advantages and disadvantages that females could have when increasing their mating rate and the possible evolutionary consequences that may result. Butterflies and moths are an ideal study system because it is easy to determine and to manipulate experimentally their mating frequency. In this study, the effect of continuous availability of different numbers of males (1, 2, 4, 8) on female mating rate and fitness components was estimated by comparing the number of spermatophores in the corpus bursa (an estimate of the number of copulations, but not of the number males involved in these copulations), female longevity, lifetime number of laid eggs (fecundity), and proportion of hatching eggs (fertility) in the moth Sangalopsis veliterna Druce (Lepidoptera: Geometridae). The results showed that there were no significant differences in either fertility or fecundity when treatments were compared, but longevity and in some cases fecundity increased when females had several matings. Resumen En la naturaleza, hembras de varios taxa animal muestran una variación considerable en su sistema de apareamiento, esta variación involucra diferentes costos (energéticos, reproductivos, etc) y beneficios (aumento de la tasa reproductiva neta de la hembra, mayor longevidad, entre otros). En años recientes, muchos estudios se han enfocado en descubrir las potenciales ventajas y desventajas que las hembras podrían tener al aumentar su número de cópulas y las posibles consecuencias evolutivas que podrían resultar. Las mariposas y polillas son un sistema de estudio ideal, dada la facilidad para determinar y manipular experimentalmente su frecuencia de apareamiento. En este estudio, el efecto de la disponibilidad continua de diferente número de machos (1, 2, 4, 8) sobre la frecuencia de apareamiento de las hembras y los componentes del potencial reproductivo (fitness) fueron estimados al comparar el número de espermatóforos hallados en la bursa copulatrix (un estimado del número de copulas, pero no del número de machos involucrados en estas copulas), la longevidad de las hembras, número de huevos colocados (fecundidad) y proporción de huevos fecundados (fertilidad) en la polilla Sangalopsis veliterna Druce (Lepidóptera: Geometridae). Los resultados indican que no existen diferencias en la fertilidad ni en la fecundidad; sin embargo la longevidad aumentó a medida que se las hembras presentaron más de una cópula y de igual manera en algunos casos la fecundidad aumentó con varios apareamientos. PMID:25205137

Alfabetización en Astronomía de docentes de Educación Primaria y de Educación Secundaria en La Plata

NASA Astrophysics Data System (ADS)

De Biasi, M. S.; Orellana, R. B.

2014-10-01

La educación de este siglo tiene como uno de sus retos alcanzar la alfabetización cientfica de todos los ciudadanos para que comprendan y tomen decisiones sobre el mundo natural y sus cambios originados por la actividad humana utilizando el conocimiento científico. En esta misión los docentes de los niveles obligatorios de enseñanza juegan un papel clave por su rol de agentes multiplicadores del conocimiento. Se requiere, entonces de una adecuada alfabetización en ciencias de los docentes o, como mínimo, que dominen los temas científicos a enseñar. En el campo de la Astronomía, numerosas investigaciones han señalado que maestros de primaria y estudiantes de profesorados poseen una escasa formación en estos temas (Camino 1995 y 1999, Gangui 2010), que frecuentemente presentan a los alumnos concepciones alternativas o no científicas de los fenómenos astronómicos cotidianos (Kriner 2004, Vega Navarro 2007, Gangui et al 2010); a lo que se suma la presentación confusa o errónea de algunos temas astronómicos en los textos escolares (Kriner 2004). Desde 2011, la Facultad de Ciencias Astronómicas y Geofísicas, UNLP, ofrece un curso de capacitación destinado a fortalecer y actualizar los contenidos académicos y didácticos de los docentes del distrito La Plata utilizando diversas estrategias didácticas. Los contenidos comprenden los temas astronómicos de los diseños curriculares vigentes. La evaluación diagnóstica de los conocimientos previos de los docentes cursantes sobre los contenidos de mayor presencia en los diseños curriculares mostró resultados similares a las investigaciones arriba mencionadas. Referente a los movimientos de la Tierra, en promedio, el 54% poseía conceptos erróneos y el 16% no los sabía; con referencia a la Luna el 56% poseía conceptos erróneos y un 4% no los sabía. Los resultados del curso mostraron que el 95% de los docentes revirtió sus conceptos previos erróneos, que adquirió criterios para la búsqueda de fuentes de información confiables y que el grado de conocimientos disciplinares y didácticos alcanzados por los docentes garantiza el efecto multiplicador de esta propuesta. Esta capacitación fue acreditada con puntaje por el organismo educativo provincial en 2011, 2012 y 2013.

Poblacion estelar joven embebida en la nube molecular galactica asociada a la fuente IRAS 18236-1205

NASA Astrophysics Data System (ADS)

Romero, Ricardo Retes

2008-06-01

En esta tesis presento una metodología de seleccion y estudio de la población estelar embebida en la nube molecular galactica asociada a la fuente IRAS 18236-1205. La fuente IRAS posee colores de region Ultra Compacta HII (UCHII) y tiene deteccióon en monosulfuro de carbono (CS), trazador molecular de alta densidad, lo cual da la posibilidad de definir la nube molecular asociada hacia esta region. Lo anterior muestra que esta es buena candidata a región de formación estelar masiva. La metodología de seleccion de la población embebida, est à basada por una parte, en la distribución del gas molecular monoxido de carbono (13CO) asociado a la fuente IRAS, nube molecular seleccionada del mapeo Galactic Ring Survey (GRS) realizado en 13CO. Otros pasos de la seleccion, se basan en los diagramas color-color y color-magnitud con datos del cercano infrarrrojo de 2MASS. Para el estudio de la componente estelar se usaron los catalogos de fuentes puntuales en el cercano, medio y lejano infrarrojo de 2MASS, SPITZER e IRAS, respectivamente. De los diagramas color-color y color-magnitud, usando datos de 2MASS, se construyo un criterio fotométrico para identificar los objetos estelares j ovenes embebidos en la region molecular. Aplicando modelos a la distribución espectral de energía (SED) de algunos ellos, se encontraron parametros estelares de objetos estelares j ovenes embebidos de masa intermedia y alta. Adicionalmente, se encontro un objeto de masa ´ intermedia no identifiado por el catalogo de 2MASS y su efecto sobre el medio interestelar, emision en la banda de [4.5] μm de IRAC-Spitzer asociado a un outflow. Dos de los objetos seleccionados por el criterio fotometrico resultaron ser objetos estelares jovenes de alta e intermedia masa (B1V/B2V y B8V/A0V respectivamente), los cuales deben estar asociados a la emision radiativa responsable de los colores de región UC HII. Otro objeto estelar joven de baja masa (F0V/F5V) fue encontrado en la region de estudio. Este parece estar asociado con la presencia de un disco circumestelar y material excitado por choque (IRAC-Spitzer [4.5]μm). Se concluye que el escenario de region de formación estelar masiva factible para esta region molecular es el de una asociación estelar joven embebida en una densa región molecular (AV . 30) hacia la fuente IRAS 18236-1205.

Male courtship behavior in Ceratitis Capitata (Diptera: Tephritidae) that have received Aromatherapy with ginger root oil

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

Briceno, D.; Eberhard, W.; Smithsonian Tropical Research Institute

The results of previous studies that showed that exposing mass-reared male Mediterranean fruit flies Ceratitis capitata (Wiedemann) to ginger root oil ('aromatherapy') increases the likelihood of mating with wild females were confirmed. The increased male success could be due to female responses to changes in male behavior or male pheromones. There were no significant differences in the types of courtship movements executed by males with and without aromatherapy. The durations of movements also did not differ when mass-reared males were paired with mass-reared females; however, when they were paired with wild females, there were a few, small differences. Previous studiesmore » indicated that the effectiveness of the male long-distance attractant pheromone is not affected by aromatherapy, but these studies did not consider pheromones released at close range during courtship, which behavioral analyses suggest may be different. We propose the following possible explanation for the different effects of aromatherapy with different females. Selection on males under mass rearing may have altered their close-range pheromones in ways that can be remedied by aromatherapy; and only wild females respond because the pheromonal responsiveness of mass-reared females has also changed. We propose observations that could test these ideas. (author) [Spanish] Los resultados de estudios previos que muestran que al exponer machos criados en masa de la mosca mediterranea de la fruta Ceratitis capitata (Wiedemann) al aceite de la raiz del jengibre ('aromaterapia') aumento la probabilidad del apareamiento con hembras naturales fueron confirmados. El aumento en el exito de los machos puede ser debido a las respuestas de las hembras a los cambios en el comportamiento o feromonas de los machos. No hubo una diferencia significativa en la clase de los movimientos del cortejo ejecutados por los machos con y sin la aromaterapia. La duracion de los movimientos tampoco fue diferente cuando los machos criados en masa fueron apareados con hembras criadas en masa; sin embargo, cuando ellos fueron apareados con hembras naturales, resultaron unas pequenas diferencias. Los estudios previos indicaron que la eficacia de la feromona atrayente de machos de larga distancia no esta afectada por la aromaterapia, pero estos estudios no consideran las feromonas sueltas en un rango corto durante el cortejo, cuando el analisis de comportamiento sugiere que puede ser diferente. Nosotros proponemos la explicacion siguiente para los efectos diferentes de la aromaterapia con las diferentes hembras. La seleccion de machos bajo condiciones de cria en masa puede haber alterado las feromonas de rango corto de manera que puede ser remediada por la aromaterapia; y solamente las hembras naturales responden por que tambien ha cambiado la respuesta de las hembras criadas en masa a la feromona. Nosotros indicamos observaciones que pueden probar estas ideas. (author)« less

A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.

PubMed

Sutherland, Megan S; Cumming, Anthony M; Bowman, Mackenzie; Bolton-Maggs, Paula H B; Bowen, Derrick J; Collins, Peter W; Hay, Charles R M; Will, Andrew M; Keeney, Stephen

2009-07-30

Direct sequencing of VWF genomic DNA in 21 patients with type 3 von Willebrand disease (VWD) failed to reveal a causative homozygous or compound heterozygous VWF genotype in 5 cases. Subsequent analysis of VWF mRNA led to the discovery of a deletion (c.221-977_532 + 7059del [p.Asp75_Gly178del]) of VWF in 7 of 12 white type 3 VWD patients from 6 unrelated families. This deletion of VWF exons 4 and 5 was absent in 9 patients of Asian origin. We developed a genomic DNA-based assay for the deletion, which also revealed its presence in 2 of 34 type 1 VWD families, segregating with VWD in an autosomal dominant fashion. The deletion was associated with a specific VWF haplotype, indicating a possible founder origin. Expression studies indicated markedly decreased secretion and defective multimerization of the mutant VWF protein. Further studies have found the mutation in additional type 1 VWD patients and in a family expressing both type 3 and type 1 VWD. The c.221-977_532 + 7059del mutation represents a previously unreported cause of both types 1 and 3 VWD. Screening for this mutation in other type 1 and type 3 VWD patient populations is required to elucidate further its overall contribution to VWD arising from quantitative deficiencies of VWF.

Simulation of groundwater drainage into a tunnel in fractured rock and numerical analysis of leakage remediation, Romeriksporten tunnel, Norway

NASA Astrophysics Data System (ADS)

Kitterød, N.-O.; Colleuille, H.; Wong, W. K.; Pedersen, T. S.

2000-09-01

Standard geostatistical methods for simulation of heterogeneity were applied to the Romeriksporten tunnel in Norway, where water was leaking through high-permeable fracture zones into the tunnel while it was under construction, causing drainage problems on the surface. After the tunnel was completed, artificial infiltration of water into wells drilled from the tunnel was implemented to control the leakage. Synthetic heterogeneity was generated at a scale sufficiently small to simulate the effects of remedial actions that were proposed to control the leakage. The flow field depends on the variance of permeabilities and the covariance model used to generate the heterogeneity. Flow channeling is the most important flow mechanism if the variance of the permeability field is large compared to the expected value. This condition makes the tunnel leakage difficult to control. The main effects of permeability changes due to sealing injection are simulated by a simple perturbation of the log-normal probability density function of the permeability. If flow channeling is the major transport mechanism of water into the tunnel, implementation of artificial infiltration of water to control the leakage requires previous chemical-sealing injection to be successful. Résumé. Des méthodes géostatistiques standard ont été employées pour simuler l'hétérogénéité des zones de fractures à fortes perméabilitées dans lesquelles, au cours de la construction du tunnel ferroviaire de Romeriksporten (Norvège), l'eau s'est écoulée, causant des problèmes de drainage en surface. Quand les travaux ont été terminés, l'injection d'eau dans des puits forés à partir du tunnel a été réalisée pour contrôler ces infiltrations. Une hétérogénéité synthétique a été créée à une échelle suffisamment petite pour simuler les effets de l'injection d'eau. Le champ des écoulements dépend de la variance des perméabilités et de la covariance du modèle utilisé pour générer l'hétérogénéité. La chenalisation de l'écoulement est le mécanisme d'écoulement le plus important si la variance du champ de perméabilité est grande par rapport à la valeur moyenne. Cette condition fait que les infiltrations dans le tunnel sont difficiles à contrôler. L'étanchéification du tunnel par des produits chimiques est simulé par une simple perturbation de la fonction de densité de probabilité log-normale de la perméabilité. Si la chenalisation de l'écoulement est le principal mécanisme de transport d'eau entrant dans le tunnel, la création d'une injection artificielle de l'eau pour contrôler l'infiltration dans le tunnel impose, pour réussir, une imperméabilisation préalable par des produits chimiques. Resumen. Se han aplicado métodos estadísticos convencionales para la simulación de la heterogeneidad en el túnel de Roeriksporte (Noruega), donde la presencia de agua en zonas fracturadas de alta permeabilidad originó problemas de drenaje en superficie durante su construcción. Una vez finalizado el túnel, para controlar la infiltración se inyectó agua en los pozos situados en su interior. La generación del campo heterogéneo se realizó a una escala lo suficientemente pequeña que permitiera simular los efectos de las medidas de control propuestas. El campo de flujo depende de la varianza de las permeabilidades y del modelo de covarianza utilizado para generar la heterogeneidad. El flujo a través de canales es el mecanismo dominante si la varianza del campo de permeabilidad es grande en relación con el valor esperado. Este hecho condiciona que las filtraciones en el túnel sean difíciles de controlar. Los principales efectos de los cambios de permeabilidad originados por las inyecciones para el sellado del túnel se simularon mediante una simple perturbación de la función de densidad de probabilidad lognormal de la permeabilidad. Si el flujo a través de canales es el principal mecanismo de la presencia de agua en el túnel, el control de las filtraciones mediante técnicas de inyección de agua en pozos de recarga requiere de la inyección previa de un producto químico para el sellado de las fisuras.

Los incendios y su salud

EPA Pesticide Factsheets

El humo de los incendios puede tener un efecto adverso en la salud de las personas, especialmente en aquellas que padecen de enfermedades cardíacas y pulmonares. Vea cómo minimizar su exposición al humo.

Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene.

PubMed

Gabbay, Monica; Ellard, Sian; De Franco, Elisa; Moisés, Regina S

2017-09-01

Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis.

Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene

PubMed Central

Gabbay, Monica; Ellard, Sian; De Franco, Elisa; Moisés, Regina S.

2017-01-01

Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis. PMID:28663161

A novel mutation in PAX3 associated with Waardenburg syndrome type I in a Chinese family.

PubMed

Xiao, Yun; Luo, Jianfen; Zhang, Fengguo; Li, Jianfeng; Han, Yuechen; Zhang, Daogong; Wang, Mingming; Ma, Yalin; Xu, Lei; Bai, Xiaohui; Wang, Haibo

2016-01-01

The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.

Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules.

PubMed

Pierson, T M; Nezhad, Mani; Tremblay, Matthew A; Lewis, Richard; Wong, Derek; Salamon, Noriko; Sicotte, Nancy

2015-10-01

A 55-year-old female presented with a 6-year history of paresthesias, incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white matter abnormalities associated with subependymal nodules. Biochemical evaluation noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3-hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene revealed compound heterozygosity consisting of a novel variant (c.1219C>G; p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

A mathematical model of chemoreception for odours and taste.

PubMed

Maurin, Francis

2002-04-07

We propose a mathematical model based on the occupation theory and on the hypothesis that, for a given stimulus, there exist two kinds of receptors. The receptors of the first kind react by a two-step process, first forming an intermediate inactive compound which is then changed into an active depolarizing form (this scheme was already used by Del Castillo & Katz, 1957). In the same way, the receptors of the second kind react by a two-step process, first forming an intermediate inactive compound which is then changed into an active hyperpolarizing form. The response is assumed to be proportional to the difference between the fraction of the active depolarizing compound and that of the active hyperpolarizing compound. The present paper deals only with the time course of the intensity of the response: in the first part, when a continuous flow of stimulus is applied and in the second part, when this continuous flow is removed. It does not deal with the quality and the discrimination of odours. The proposed mathematical model accounts for the depolarizing responses (which are the most frequent ones), the hyperpolarizing responses, the mixed responses reported by Patte et al. (1989), the off-responses reported by Takagi & Shibuya (1959) and for their variability, and the latent period in the olfactory response (Ottoson, 1974). Copyright 2002 Elsevier Science Ltd. All rights reserved.

Frequency of canine nt230(del4) MDR1 mutation in prone pure breeds, their crosses and mongrels in Israel - insights from a worldwide comparative perspective.

PubMed

Dekel, Yaron; Machluf, Yossy; Stoler, Aviad; Aderet, Arava; Baumel, Daniel; Kellerman, Efrat; Plotsky, Yoram; Noked Partouche, Oshrat; Elhalal, Gal; Ben-Shlomo, Izhar; Bercovich, Dani

2017-11-13

Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan. The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds. This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.

INTERVENCIÓN EDUCATIVA EFECTIVA EN VIH PARA MUJERES

PubMed Central

Miner, Sarah; Poupin, Lauren; Bernales, Margarita; Ferrer, Lilian; Cianelli, Rosina

2016-01-01

RESUMEN En Chile se estima que aproximadamente 38 mil personas viven con el Virus de Inmunodeficiencia Humana [VIH]. En el año 2001, 1.092 mujeres chilenas vivían con VIH, actualmente se cree que hay más de 7.600 mujeres con el virus. Frente a estas cifras surge la necesidad de crear estrategias de prevención dirigidas a mujeres chilenas. Objetivo analizar los estudios ya realizados en la prevención de VIH para determinar qué aspectos se deben incluir en programas exitosos de prevención de VIH en mujeres. Diseño y Método se realizó una revisión de la literatura utilizando la base de datos Proquest, CINAHL, Pubmed y Scielo. Los límites comprendieron: textos completos, de los últimos 10 años, de acceso gratuito y escrito en español o inglés. Se seleccionaron 15 artículos para la revisión. Resultados todos los artículos comprenden la evaluación del efecto de una intervención sobre conocimiento y conductas relacionadas con VIH/SIDA. Catorce muestran resultados significativos en cambios positivos de conducta o conocimientos relacionados con la prevención de VIH. Conclusiones los programas de prevención de VIH en mujeres pueden ser efectivos para lograr cambios de conducta y de conocimiento. Las intervenciones exitosas son aquellas basadas en teorías o modelos de prevención y en cambios de conductas, todas adaptadas a la cultura de la población estudiada. PMID:27667897

Mutation analysis in the long isoform of USH2A in American patients with Usher Syndrome type II.

PubMed

Yan, Denise; Ouyang, Xiaomei; Patterson, D Michael; Du, Li Lin; Jacobson, Samuel G; Liu, Xue-Zhong

2009-12-01

Usher syndrome type II (USH2) is an autosomal recessive disorder characterized by moderate to severe hearing impairment and progressive visual loss due to retinitis pigmentosa (RP). To identify novel mutations and determine the frequency of USH2A mutations as a cause of USH2, we have carried out mutation screening of all 72 coding exons and exon-intron splice sites of the USH2A gene. A total of 20 USH2 American probands of European descent were analyzed using single strand conformational polymorphism (SSCP) and direct sequencing methods. Ten different USH2A mutations were identified in 55% of the probands, five of which were novel mutations. The detected mutations include three missense, three frameshifts and four nonsense mutations, with c.2299delG/p.E767fs mutation, accounting for 38.9% of the pathological alleles. Two cases were homozygotes, two cases were compound heterozygotes and one case had complex allele with three variants. In seven probands, only one USH2A mutation was detected and no pathological mutation was found in the remaining eight individuals. Altogether, our data support the fact that c.2299delG/p.E767fs is indeed the most common USH2A mutation found in USH2 patients of European Caucasian background. Thus, if screening for mutations in USH2A is considered, it is reasonable to screen for the c.2299delG mutation first.

Evolución de estrellas enanas blancas de Helio de masa baja e intermedia

NASA Astrophysics Data System (ADS)

Althaus, L. G.; Benvenuto, O. G.

Numerosas observaciones realizadas particularmente en los últimos dos años parecen confirmar que las enanas blancas (EB) de helio de masa baja e intermedia son el resultado de la evolución de sistemas binarios cercanos. Con el objeto de realizar una adecuada interpretación de estos objetos son necesarios modelos de EBs de helio lo más detallado posibles. En este estudio presentamos cálculos detallados de la evolución de EBs de helio con masas entre M=0.1Msolar y M=0.5Msolar a intervalos de 0.05Msolar . Para ello, hemos tenido en cuenta los efectos de temperatura finita mediante un código de evolución estelar lo más actualizado posible. En particular, el transporte de energía es descripto en el marco del nuevo modelo para la convección turbulenta desarrollado por Canuto - Mazzitelli. Además hemos considerado la nueva ecuación de estado para plasmas de helio de Saumon et al. y nuevas opacidades radiativas OPAL. Las pérdidas por neutrinos fueron asimismo tenidas en cuenta. Excepto para las EBs más masivas, nuestros modelos iniciales están ubicados en las cercanías de la correspondiente línea de Hayashi para configuraciones de helio. Nuestros resultados muestran que existe una región prohibida en el diagrama observacional HR donde ninguna EB de helio puede encontrarse. Dicha región es para log{(L/Lsolar )}>= -0.25 and log{Teff} >= 4.45. Hemos encontrado también que los tracks evolutivos en el diagrama HR en el dominio de alta luminosidad (pre - EB) son fuertemente afectados por la eficiencia convectiva y que las pérdidas por neutrinos son importantes en los modelos más masivos. Finalmente hemos analizado la estructura de la zona convectiva externa encontrando que la teoría de Canuto - Mazzitelli conduce a un perfil convectivo muy diferente del dado por cualquier versión de la popular teoría de la mixing length. Si bién este comportamiento es decisivo en el contexto de las inestabilides pulsacionales, los radios y gravedades superficiales de los modelos no son afectados al incluir la nueva teoría de convección.

Preclinical atherosclerosis at the time of pre-eclamptic pregnancy and up to 10 years postpartum: systematic review and meta-analysis.

PubMed

Milic, N M; Milin-Lazovic, J; Weissgerber, T L; Trajkovic, G; White, W M; Garovic, V D

2017-01-01

Pre-eclampsia (PE) is a pregnancy-specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early-stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima-media thickness (CIMT), compared with women without PE. We conducted a systematic review and meta-analysis of studies that reported CIMT, a non-invasive, ultrasound-based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Heterogeneity was assessed using the I 2 statistic. Standardized mean difference (SMD) was used as a measure of effect size. Fourteen studies were included in the meta-analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73-1.48); P < 0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36-0.79); P < 0.001). Atherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. La preeclampsia (PE) es un trastorno hipertensivo específico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguíneos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerótica, según lo determinado por el espesor del complejo íntima-media de la arteria carótida (CIMT, por sus siglas en inglés), en comparación con las mujeres sin PE. MÉTODOS: Se realizó una revisión sistemática y un metaanálisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclínica obtenida mediante ecografía, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera década después del parto, y en los que se midió el CIMT en la arteria carótida común. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los títulos y los resúmenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluación de calidad. La heterogeneidad se evaluó mediante el test estadístico I 2 . Se usó la diferencia de medias estandarizada (SMD, por sus siglas en inglés) como una medida de la magnitud del efecto. En el metaanálisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 años después del parto y tres incluyeron mediciones tomadas en ambos períodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenían, tanto en el momento del diagnóstico (SMD 1,10 (I 95%, 0,73-1,48), P <0,001) como en la primera década después del parto (SMD 0,58 (IC 95%, 0,36-0,79), P <0,001). La carga aterosclerótica está presente en el momento de la PE y podría ser un mecanismo asociado con esta enfermedad. La medición del CIMT puede ofrecer una oportunidad para la identificación temprana de mujeres premenopáusicas con carga aterosclerótica después de un embarazo con PE. : (pre-eclampsia,PE),,,。-(carotid intima-media thickness,CIMT),PEPE,。 : PEPECIMTmeta,CIMT、。:10CIMT。PubMed、EMBASEWeb of Science,201637。,,、。I 2 。(SMD)。 : meta14。7PE,1010,3。PEPE,[SMD,1.10(95% CI,0.73~1.48);P<0.001]10[SMD,0.58(95% CI,0.36~0.79);P<0.001] CIMT。 : PE,。CIMT,PE。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effects of Wind Energy Development on Nesting Ecology of Greater Prairie-Chickens in Fragmented Grasslands

PubMed Central

McNew, Lance B; Hunt, Lyla M; Gregory, Andrew J; Wisely, Samantha M; Sandercock, Brett K

2014-01-01

Wind energy is targeted to meet 20% of U.S. energy needs by 2030, but new sites for development of renewable energy may overlap with important habitats of declining populations of grassland birds. Greater Prairie-Chickens (Tympanuchus cupido) are an obligate grassland bird species predicted to respond negatively to energy development. We used a modified before–after control–impact design to test for impacts of a wind energy development on the reproductive ecology of prairie-chickens in a 5-year study. We located 59 and 185 nests before and after development, respectively, of a 201 MW wind energy facility in Greater Prairie-Chicken nesting habitat and assessed nest site selection and nest survival relative to proximity to wind energy infrastructure and habitat conditions. Proximity to turbines did not negatively affect nest site selection (β = 0.03, 95% CI = −1.2–1.3) or nest survival (β = −0.3, 95% CI = −0.6–0.1). Instead, nest site selection and survival were strongly related to vegetative cover and other local conditions determined by management for cattle production. Integration of our project results with previous reports of behavioral avoidance of oil and gas facilities by other species of prairie grouse suggests new avenues for research to mitigate impacts of energy development. Efectos del Desarrollo de la Energía Eólica sobre la Ecología de Anidación de Gallinas de la Gran Pradera en Pastizales Fragmentados Resumen Se calcula que la energía eólica aportará el 20% de las necesidades energéticas de los Estados Unidos para el 2030, pero nuevos sitios para el desarrollo de energía renovable pueden traslaparse con hábitats importantes de poblaciones declinantes de aves de pastizal. La gallina de la Gran Pradera (Tympanuchus cupido) es una especie de ave obligada de pastizal que se pronostica responderá negativamente al desarrollo energético. Usamos un diseño ADCI modificado para probar los impactos del desarrollo de la energía eólica sobre la ecología reproductiva de las gallinas en un estudio de 5 años. Ubicamos 59 y 185 nidos antes y después del desarrollo, respectivamente, de una instalación de energía eólica de 201 MW en el hábitat de anidación de las gallinas y estudiamos la selección de sitio de anidación y la supervivencia de nidos en relación con la proximidad a la infraestructura y las condiciones de hábitat. La proximidad con las turbinas no afectó negativamente a la selección de sitios de anidación (β = -0.3, 95% CI = -0.6–0.1). En su lugar, la selección de sitios de anidación y la supervivencia estuvieron fuertemente relacionadas con la cobertura vegetal y otras condiciones locales determinadas por el manejo de la producción de ganado. La integración de los resultados de nuestro proyecto con reportes previos de la evitación conductual de instalaciones de petróleo y gas por otras especies de pastizales sugiere nuevas vías para que la investigación mitigue los impactos del desarrollo energético. PMID:24628394

A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a Chinese family.

PubMed

He, Xiaoguang; Peng, Qi; Li, Siping; Zhu, Pengyuan; Wu, Chunqiu; Rao, Chunbao; Lin, Jingqi; Lu, Xiaomei

2017-08-01

We aimed to investigate the genetic causes of hearing loss in a Chinese proband with autosomal recessive congenital deafness. The targeted capture of 159 known deafness genes and next-generation sequencing were performed to study the genetic causes of hearing loss in the Chinese family. Sanger sequencing was employed to verify the variant mutations in members of this family. The proband harbored two mutations in the MYO7A gene in the form of compound heterozygosity. She was found to be heterozygous for a novel insertion mutation c.3847_3848 ins TCTG (p.N1285LfsX24) in exon 30 and for the known mutation c.2239_2240delAG (p.R747S fsX16)in exon 19. The novel mutation was absent in the 1000 Genomes Project. These variants were carried in the heterozygous state by the parents and were therefore co-segregated with the genetic disease. Clinical re-assessment, including detailed audiologic and ocular examinations, revealed congenital deafness and retinitis pigmentosa in the proband. Collectively, the combination of audiometric, ophthalmologic and genetic examinations successfully confirmed the phenotype of Usher syndrome type 1 (USH1). This study demonstrates that the novel mutation c.3847_3848insTCTG (p. N1285LfsX24) in compound heterozygosity with c.2239_2240delAG in the MYO7A gene is the main cause of USH1 in the proband. Our study expands the mutational spectrum of MYO7A and provides a foundation for further investigations elucidating the MYO7A-related mechanisms of USH1. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca.

PubMed

Ezzat, Shahira Mohammed; Abdel Motaal, Amira; El Awdan, Sally Abdel Wanees

2017-12-01

Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear. Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds. A bio-guided protocol based on the evaluation of α-glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks. Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-β-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3β,16β,20(R)-trio1-3-O-β-d-glucopyranoside; a furostanol saponin, (3) 26-(O-β-d-glucopyranosyl)-22-O-methylfurost-5-ene-3β,26-diol-3-O-β-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC 50  = 3.12 ± 0.17 and 1.04 ± 0.02 μg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively. We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications.

The Chemical Chaperone Phenylbutyrate Rescues MCT8 Mutations Associated With Milder Phenotypes in Patients With Allan-Herndon-Dudley Syndrome.

PubMed

Braun, Doreen; Schweizer, Ulrich

2017-03-01

Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) prevent appropriate entry of thyroid hormones into brain cells during development and cause severe mental retardation in affected patients. The current treatment options are thyromimetic compounds that enter the brain independently of MCT8. Some MCT8-deficient patients (e.g., those carrying MCT8delF501) will not be as severely affected as most others. We have shown that the MCT8delF501 protein has decreased protein stability but important residual function once it reaches the plasma membrane. We were able to rescue protein expression and the function of MCT8delF501 in a Madin-Darby canine kidney cell model by application of the chemical chaperone sodium phenylbutyrate (NaPB), a drug that has been used to treat patients with cystic fibrosis and urea cycle defects for extended periods of time. In the present study, we have extended our previous study and report on the NaPB-dependent rescue of a series of other pathogenic MCT8 mutants associated with milder patient phenotypes. We show that NaPB can functionally rescue the expression and activities of Ser194Phe, Ser290Phe, Leu434Trp, Arg445Cys, Leu492Pro, and Leu568Pro mutations in MCT8 in a dose-dependent manner. The soy isoflavone genistein, a dietary supplement, which was effective in MCT8delF501, was also effective in increasing the expression and transport of these MCT8 mutants; however, the effect size differed among mutants. Kinetic analyses revealed that the Michaelis constants of the mutants toward the primary substrate 3,3',5-triiodothyronine were not much different from the wild-type value, suggesting that these mutants are not impaired in their interaction with substrate but rather destabilized by the mutation and degraded. Copyright © 2017 by the Endocrine Society.

Caracterización espectroscópica de hielos de interés atmosférico y astrofísico

NASA Astrophysics Data System (ADS)

Escribano, R.

En años recientes se ha incrementado el estudio de procesos físicos y químicos que tienen lugar en la superficie o el interior de hielos, tanto en medios astrofísicos como en la atmósfera terrestre y en otros cuerpos del sistema solar. Se ha comprobado que las partículas heladas actúan como catalizadores de reacciones químicas, que no ocurrirían en su ausencia. En la atmósfera terrestre, es bien conocida la importancia de partículas de hidratos de ácido nítrico, formando las llamadas nubes estratosféricas polares, en los procesos de destrucción de ozono estratosférico. En hielos astrofísicos, átomos como H, C, N y O pueden adherirse o introducirse en la estructura cristalina o amorfa del hielo, y dar lugar a reacciones de formación de moléculas evitando su barrera de activación. Existen partículas heladas en el medio interestelar formando parte de las llamadas nubes moleculares densas y frías, con valores del orden de 106 átomos de H por cm3 y temperaturas entre 3 y 90 K. Alrededor de protoestrellas, pueden formarse hielos de distinta composición, polares o apolares, en las zonas de alejamiento y temperatura decreciente a partir del núcleo caliente. Por su parte, los cometas están formados por un núcleo de hielo y rocas, sobre el que se encuentran adheridas moléculas gaseosas, y una cola, formada por los gases liberados por efecto del calentamiento debido a la radiación solar incidente. En nuestro sistema solar, los polos de La Tierra y de Marte están cubiertos de hielo, así como la mayoría de los cuerpos externos. Los satélites de Júpiter han sido estudiados detalladamente, y se han encontrado en ellos, y en Tritón (satélite de Neptuno), hielos de moléculas como SON2, CO2, N2, CH4 y otros. Para la caracterización espectroscópica de estos hielos se precisan medidas en el laboratorio, aún conociendo la imposibilidad intrínseca de reproducir exactamente las condiciones en que se formaron y se encuentran en los medios astrofísicos. El montaje experimental requiere un sistema que permita alcanzar bajas presiones y temperaturas, formado usualmente por una cámara en cuyo interior se forman películas de hielo de la composición deseada, depositadas sobre un sustrato inerte. Las películas pueden ser a continuación tratadas por diversas técnicas, tales como irradiación UV, bombardeo con electrones o iones, calentamiento y enfriamiento, etc. Habitualmente todos los procesos se controlan por espectroscopía de infrarrojo. La radiación proveniente de un espectrómetro se hace incidir sobre la muestra y se extrae de la cámara mediante ventanas, y se enfoca posteriormente sobre el detector. En el laboratorio de Física Molecular del Instituto de Estructura de la Materia disponemos de un montaje experimental diseñado para el estudio de partículas de hielo similares a las formadas en las nubes estratosféricas polares de nuestra atmósfera. El montaje es similar al descrito anteriormente, excepto en lo que se refiere a las condiciones de presión y temperatura, que son menos estrictas en nuestros experimentos. La extensión de estas condiciones de trabajo a las requeridas en medios astrofísicos es una posibilidad a discutir. Por otra parte, disponemos de un método de cálculo de estructuras periódicas, basado en el programa SIESTA (acrónimo de Spanish Initiative for Electronic Simulations of Thousands of Atoms), que ha proporcionado excelentes resultados en lo relativo a la determinación de estructuras cristalinas y predicción de su espectro infrarrojo, en los sistemas estudiados hasta la fecha, es decir, los hidratos de ácido nítrico de interés atmosféricos. Su aplicación para el estudio de hielos de relevancia astrofísica podría ser del máximo interés.

The effects of acupressure on labor pains during child birth: randomized clinical trial.

PubMed

Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

2016-08-08

to analyze the effects of acupressure on the sanyinjiao point for pregnant women in labor at public maternity wards. single-blind controlled clinical trial, randomly done employing a pragmatic profile. We selected 156 pregnant women in their ≥ 37 week/s, who had cervical dilations of ≥ 4 cm and with two or more contractions in 10 minutes. The pregnant women were randomly divided into three groups at a university hospital in the suburbs of Sao Paulo, Brazil, in order to receive either acupressure treatment, a placebo or participate as part of a control group. The acupressure was applied on the sanyinjiao point during the contractions for 20 minutes. Then the intensity of the pain was evaluated using the Visual Analogue Scale (VAS). The averages for the pain measured using the VAS were not different for the three groups that were a part of the study (p-value=0.0929), however they were less in the acupressure groups immediately after receiving the treatment (p-value=<0.0001). This was also the case where the treatment lasted for 1 hour (p-value=0.0001). This was the case in comparison with placebo and control groups. the use of acupressure on the sanyinjiao point is a useful way to alleviate pain in a non-invasive manner. It can improve the quality of care given to pregnant women in labor. Register: RBR-9mhs8r. analisar os efeitos da acupressão no ponto sanyinjiao sobre a dor na fase ativa do trabalho de parto, em gestantes atendidas em maternidade pública. trata-se de um ensaio clínico controlado e randomizado, simples-cego e de caráter pragmático. Foram selecionadas 156 mulheres com idade gestacional ≥ 37 semanas, dilatação cervical ≥ 4 cm e com duas ou mais contrações em 10 minutos. As gestantes foram divididas aleatoriamente em três grupos em um hospital universitário do interior do estado de São Paulo, Brasil, para receber acupressão, placebo ou participar como controle. A acupressão foi aplicada no ponto sanyinjiao durante as contrações, por 20 minutos, e a intensidade da dor avaliada por meio de uma Escala Analógica Visual (EAV). as médias de dor pela EAV não foram diferentes nos três grupos na admissão (p-valor=0,0929), porém foram menores no grupo de acupressão imediatamente após (p-valor=<0,0001) e com 1 h do tratamento (p-valor=0,0001) ao se comparar com placebo e controle. a acupressão no ponto sanyinjiao se mostrou uma medida útil no alívio da dor, não invasiva e um meio de melhorar a qualidade dos cuidados a parturiente. Registro: RBR-9mhs8r. analizar los efectos de la acupresión, en el punto sanyinjiao, sobre el dolor en la fase activa del trabajo de parto, en embarazadas atendidas en maternidad pública. ensayo clínico controlado y aleatorio, simple ciego y de carácter pragmático. Fueron seleccionadas 156 mujeres con edad gestacional ≥ 37 semanas, dilatación cervical ≥ 4 cm y con dos o más contracciones en 10 minutos. Las embarazadas fueron divididas aleatoriamente en tres grupos en un hospital universitario del interior del estado de Sao Paulo, Brasil, para recibir acupresión, placebo o participar como control. La acupresión fue aplicada en el punto sanyinjiao durante las contracciones, por 20 minutos; la intensidad del dolor fue evaluada por medio de una Escala Analógica Visual (EAV). los promedios del dolor por la EAV no fueron diferentes en los tres grupos en la admisión (valor p=0,0929), sin embargo fueron menores en el grupo de acupresión inmediatamente después (valor p=<0,0001) y también después de 1 hora del tratamiento (valor p=0,0001) al compararse con el placebo y control. la acupresión en el punto sanyinjiao se mostró una medida útil en el alivio del dolor, no invasiva y un medio de mejorar la calidad de los cuidados la parturienta. Registro: RBR-9mhs8r.

Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome

PubMed Central

Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

2014-01-01

Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

Consensus QSAR model for identifying novel H5N1 inhibitors.

PubMed

Sharma, Nitin; Yap, Chun Wei

2012-08-01

Due to the importance of neuraminidase in the pathogenesis of influenza virus infection, it has been regarded as the most important drug target for the treatment of influenza. Resistance to currently available drugs and new findings related to structure of the protein requires novel neuraminidase 1 (N1) inhibitors. In this study, a consensus QSAR model with defined applicability domain (AD) was developed using published N1 inhibitors. The consensus model was validated using an external validation set. The model achieved high sensitivity, specificity, and overall accuracy along with low false positive rate (FPR) and false discovery rate (FDR). The performance of model on the external validation set and training set were comparable, thus it was unlikely to be overfitted. The low FPR and low FDR will increase its accuracy in screening large chemical libraries. Screening of ZINC library resulted in 64,772 compounds as probable N1 inhibitors, while 173,674 compounds were defined to be outside the AD of the consensus model. The advantage of the current model is that it was developed using a large and diverse dataset and has a defined AD which prevents its use on compounds that it is not capable of predicting. The consensus model developed in this study is made available via the free software, PaDEL-DDPredictor.

Clinical expression of patients with the D1152H CFTR mutation.

PubMed

Terlizzi, Vito; Carnovale, Vincenzo; Castaldo, Giuseppe; Castellani, Carlo; Cirilli, Natalia; Colombo, Carla; Corti, Fabiola; Cresta, Federico; D'Adda, Alice; Lucarelli, Marco; Lucidi, Vincenzina; Macchiaroli, Annamaria; Madarena, Elisa; Padoan, Rita; Quattrucci, Serena; Salvatore, Donatello; Zarrilli, Federica; Raia, Valeria

2015-07-01

Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Land subsidence caused by groundwater exploitation in Suzhou City, China

NASA Astrophysics Data System (ADS)

Chen, Chongxi; Pei, Shunping; Jiao, Jiu Jimmy

2002-09-01

Suzhou City, located at the lower reaches of the Yangtze River in southeastern Jiangsu Province, is one of the few cities in China which suffer from severe ground settlement. A research project was carried out to investigate this problem. Geological and hydrogeological studies show that there is a multi-layered aquifer system with three distinct, soft mud layers of marine and lagoonal origins. An examination of historical records of groundwater extraction, water levels, and ground settlement shows that the ground subsidence is associated with the continuously increasing groundwater extraction in the deep, confined aquifer. It is believed that the consolidation of the soft mud layers, especially the third layer which is thick and close to the main pumped aquifer, contributes to the ground settlement. A three-dimensional finite difference numerical model representing the multi-layered aquifer system was developed to study the ground settlement in response to groundwater extraction. By calibrating the model with both the measured groundwater level and ground settlement, the aquifer parameters were estimated. The model outputs fit reasonably well with the observed results, which indicates that the numerical model can reproduce the dynamic processes of both groundwater flow and soil consolidation. The hydraulic conductivity of the third mud layer near the center of the ground settlement has been reduced by over 30% in the last 14 years. The gradual deterioration in the hydraulic conductivity of the mud may have significant adverse effect on the sustainable groundwater resource of the deep confined aquifer, since the recharge from the shallow aquifers through the mud layer is the only source of water to the deep aquifer. An analysis of the spatial distributions of groundwater drawdown and ground settlement shows that the area with maximum drawdown is not necessarily the area with maximum ground settlement due to the occurrence of the soft mud layer. A simple reallocation in pumping rates on the basis of the spatial distribution of the thick mud layer could significantly reduce the ground settlement. Résumé. La ville de Suzhou, située dans la basse vallée du fleuve Yangtsé dans le sud-est de la province de Jiangsu, est l'une des rares villes de Chine qui souffrent cruellement de tassements du sol. Un projet de recherche a été mené pour étudier ce problème. Des études géologiques et hydrogéologiques montrent qu'il existe un système aquifère multicouche constitué de trois niveaux distincts de limons non consolidés d'origine marine et lagunaire. Un examen des historiques des prélèvements d'eau souterraine, des niveaux de nappe et des tassements de sol montrent que la subsidence du sol est associée à des prélèvements continuellement croissants d'eau souterraine dans l'aquifère captif profond. On pense que le compactage des couches limoneuses non consolidées, en particulier de la troisième couche qui est épaisse et proche du principal aquifère pompé, contribue aux tassements du sol. Un modèle numérique aux différences finies en trois dimensions, représentant l'aquifère multicouche, a été réalisé pour étudier les tassements du sol en réponse aux prélèvements d'eau souterraine. Les paramètres de l'aquifère ont été estimés par calibration du modèle au moyen à la fois des niveaux piézométriques et des tassements du sol. Les résultats de la simulation s'ajustent convenablement aux résultats observés, ce qui indique que le modèle numérique peut reproduire les processus dynamiques aussi bien des écoulements souterrains que de compactage du sol. La conductivité hydraulique de la troisième couche de limon non consolidé au voisinage du centre du tassement de sol a été réduit de plus de 30% au cours des 14 dernières années. La dégradation progressive de la conductivité hydraulique du limon peut avoir un effet significatif néfaste sur la pérennité de la ressource en eau souterraine dans l'aquifère captif profond, puisque la recharge à partir des aquifères superficiels au travers de la couche de limon est la seule alimentation de l'aquifère profond. Une analyse des distributions spatiales de l'abaissement du niveau piézométrique et des tassements du sol montre que la région soumise à l'abaissement maximal de piézométrie n'est pas nécessairement celle des tassements maximaux du sol liés à la présence de la couche de limon non consolidé. Une simple révision des débits de pompage basée sur la distribution spatiale de la couche de limon épaisse peut réduire significativement les tassements du sol. Resumen. La ciudad de Suzhou, situada en el tramo inferior del Río Yangtze, al sudeste de la provincia de Jiangsu, es una de las pocas ciudades chinas que padece problemas serios de subsidencia. Esto ha motivado la realización de un proyecto de investigación en la zona. Estudios geológicos e hidrogeológicos apuntan a un modelo de acuífero multicapa, con tres niveles distintos de lodos blandos de orígenes marino y lacustre. Examinando los registros históricos de extracciones de agua subterránea, así como de nivel piezométrico y de subsidencia, se observa que ésta se halla asociada al bombeo cada vez mayor del acuífero confinado profundo. La hipótesis es que las capas de lodos blandos se van consolidando, si bien la que más contribuye a ello es la tercera, potente y próxima al acuífero más explotado. Se ha realizado un modelo numérico tridimensional en diferencias finitas que representa el sistema acuífero multicapa, con lo que se puede estudiar el efecto de la extracción de agua subterránea en la subsidencia. Calibrando el modelo con niveles piezométricos medidos y con datos de subsidencia, se ha podido estimar los parámetros del acuífero. Los resultados del modelo ajustan de forma razonable con los datos medidos, por lo que el modelo numérico es capaz de reproducir los procesos dinámicos de flujo de aguas subterráneas y consolidación del terreno. La conductividad hidráulica de la tercera capa de lodo cerca del centro de asentamiento se ha reducido en más del 30% durante los últimos 14 años. El deterioro gradual de la conductividad hidráulica del lodo puede tener efectos adversos notables en la sustentabilidad de los recursos de agua subterránea del acuífero confinado profundo, ya que se recarga exclusivamente de acuíferos más someros a través de la capa de lodo. El análisis de la distribución espacial de descenso del nivel piezométrico y de subsidencia muestra que el área de extracción máxima no coincide necesariamente con la de máxima subsidencia, debido a la existencia de la capa de lodos blandos. Una mera redistribución de los caudales de bombeo en función de las propiedades espaciales de la gruesa capa de lodos podría reducir drásticamente los problemas de subsidencia.

Using environmental isotopes in the study of the recharge-discharge mechanisms of the Yarmouk catchment area in Jordan

NASA Astrophysics Data System (ADS)

Salameh, Elias

The recharge sources, the flow mechanisms and discharge areas of the different groundwater bodies underlying the Yarmouk River catchment area in Jordan, have, until now, not been adequately explained, although a wide range of hydrological, hydrogeological, and hydrochemical studies have been done. Along the Jordanian part of the catchment area of the Yarmouk River, groundwater issues from different aquifers with a variety of chemistries and types within the same aquifer and in between the different aquifers. Conventional recharge/discharge mechanisms, water balances and chemical analyses did not adequately explain the chemical variations and the different water types found in the area. Applying environmental isotopic tools combined with their altitude effects due to topographic variations (250-1,300 m a.s.l. within a distance of 20 km), and taking into consideration re-evaporation effects on the isotopic depletion and enrichment of rainwater, has greatly helped in understanding the recharge discharge mechanisms of the different aquifers. Precipitation along the highlands of an average of 600 mm/year is found to be depleted in its isotopic content of δO18 = -7.0 to -7.26 and δD = -32.2 to -33.28, whereas that of the Jordan Valley of 350 mm/year is highly enriched in isotopes with δO18 = -4.06 and δD = -14.5. The groundwater recharged along the highlands is depleted in isotopes (δO18 = -6, δD = -30), groundwater at the intermediate elevations is enriched (δO18 = -5, δD = -23) and that of the Jordan Valley aquifers containing meteoric water is highly enriched (δO18 -3.8, δD = -18). The deep aquifers in the Jordan Valley foothills are depleted in isotopes (δO18 -18 = -6, δD = -30) and resemble those of the highland aquifers. Only through using isotopes as a tool, were the sources of the different groundwater bodies and recharge and discharge mechanisms unambiguously explained. It was found that recharge takes place all over the study area and produces groundwater, which, from the highlands towards the Jordan Valley, shows increasing enrichment in isotopes. The highlands aquifer, with its groundwater depleted in isotopes, becomes confined towards the Jordan Valley; and, due to its confining pressure, leaks water upwards into the overlying aquifers causing their water to become less enriched in isotopes. Water depleted in its isotopic composition also seeps upward to the ground surface at the mountain foothills through faults and fissures. Les zones de recharge, les mécanismes d'écoulement et les zones de décharges des différentes masses d'eau souterraine sous le bassin versant de la rivière Yarmouk en Jordanie, étaient expliquées de manière ambiguë par les seuls outils isotopiques. Le long de la parti Jordanienne du bassin versant de la rivière Yarmouk l'eau souterraine provient de différents aquifères et se distinguent par leur type et leur composition chimique, selon que l'eau provient du même ou des différents aquifères. Les mécanismes conventionnels de recharge et de décharge, bilan hydrologique ne donnaient pas d'explications satisfaisantes concernant les variations chimiques et les différents types d'eau. En appliquant les isotopes environnementaux combinés aux effets de l'altitude sur les variations des teneurs isotopiques (l'altitude varie de 250 à 1,300 m sur une distance de 20 km.) et en prenant en considération les effets de ré-évaporation sur l'appauvrissement et l'enrichissement isotopique des eaux pluviales ont fortement contribués à une meilleure compréhension des mécanismes de recharge des différents aquifères. Les précipitations annuelles sont comprises entre 600 mm dans les zones en altitude et 350 mm dans la vallée de la Jordanie. Les écoulements de l'eau souterraine sont dirigés des zones en altitude vers la vallée de la Jordanie. Les eaux souterraines des zones en altitude sont isotopiquement appauvries (δO18 = -6, δD = -30), les eaux souterraines des zones de moyenne altitude sont enrichies (δO18 = -5, δD = -23) et les eaux de la vallée très enrichies (δO18 -3.8, δD = -18). Les aquifers profonds dans la vallée de la Jordanie sont appauvris (δO18 -18 = -6, δD = -30) et se confondent avec les eaux des zones situées en altitude. En appliquant uniquement les isotopes environnementaux comme des outils de compréhension des phénomènes hydrogéologiques, la source des différentes masses d'eau souterraines, les mécanismes de la recharge et de la décharge pourraient être expliqués de manière ambiguë. Las fuentes de recarga, los mecanismos de flujo y las áreas de descarga de los diferentes cuerpos de agua subterránea que subyacen el área de la cuenca del Río Yarmouk en Jordania, se han explicado de manera no ambigua únicamente mediante la aplicación de los isótopos como herramienta. A lo largo de la parte Jordana del área de la cuenca del Río Yarmouk el agua subterránea emerge de diferentes acuíferos con una variedad de tipos y composiciones, ya sea que provengan del mismo acuífero o de diferentes acuíferos. Los mecanismos convencionales de recarga/descarga, balances hídricos y variaciones químicas no han podido explicar las variaciones químicas y los diferentes tipos de aguas. La aplicación de herramientas de isótopos ambientales combinadas con los efectos de altitud derivados de variaciones topográficas (250 hasta 1,300 m s.n.m. en una distancia de 20 km) y tomando en consideración los efectos de re-evaporación en el empobrecimiento de isótopos y enriquecimiento del agua de lluvia han ayudado fuertemente en el entendimiento de los mecanismos de recarga/descarga de los diferentes acuíferos. La precipitación en el área varía de 600 mm/año, a lo largo de las tierras altas, a 350 mm/año en el área del Valle Jordán. El flujo de agua subterránea ocurre de las tierras altas hacia el Valle Jordán. El agua subterránea de las tierras altas está empobrecida en isótopos (δO18 = -6, δD = -30), el agua subterránea de elevaciones intermedias está enriquecida (δO18 = -5, δD = -23), y el agua de los acuíferos del Valle Jordan contiene agua meteórica que se encuentra altamente enriquecida (δO18 = -3.8, δD = -18). Los acuíferos profundos que se localizan al pie de las tierras altas del Valle Jordán están empobrecidos en isótopos (δO18 = -6, δD = -30) y son similares a los acuíferos de las tierras altas. Solo al aplicar los isótopos ambientales como herramienta pudo explicarse de manera inequívoca las fuentes de los diferentes cuerpos de agua subterránea y los mecanismos de recarga y descarga.

Occurrence, fate and ecotoxicological risk of personal care products in urban river-groundwater interface

NASA Astrophysics Data System (ADS)

Jurado, Anna; Pau Serra, Maria; Díaz-Cruz, M. Silvia; Vázquez-Suñé, Enric; Pujades, Estanislao; Barceló, Damià

2016-04-01

This work presents the occurrence and fate of selected personal care products (PCPs) in the urban river-groundwater interface. To this end, urban groundwater and river samples were collected in Sant Adrià del Besòs (NE of Spain) and a total of 16 PCPs were analyzed including benzophenone derivatives, camphor derivatives, p-aminobenzoic acid derivatives, triazoles and parabens in three different campaigns (from May 2010 to July 2014). These compounds reach the aquifer through the recharge of River Besòs that receives large amounts of effluents from waste water treatment plants. Results shown that most of compounds were not or barely detected (maximum concentrations around 30 ng/L) in groundwater samples during the different sampling campaigns. Only two triazoles, named as benzotriazole (BZT) and methyl benzotriazol (MeBZT) were found at high concentrations in groundwater samples (maximum concentration around 2000 ng/L). The fate of PCPs in the aquifer was assessed using mixing analysis considering the temporal variability of the River Besòs. Overall, measured groundwater concentrations were significantly much lower than those estimated by the mixing of the river water. This observation suggested that most of the PCPs are naturally removed when river water infiltrates the aquifer. However, some compounds were more persistent in the aquifer. These compounds were in descending order: the triazoles MeBZT and BZT followed by the camphor derivative 4MBC. The measured concentrations allowed us to assess the environmental risk posed by the selected UV-Fs (e.g. benzophenone derivatives) in the river-groundwater samples. Hazard Quotients (HQs) for diferent aquatic species were calculated in order to characterise the ecotoxicity potential of the studied compounds in the river-groundwater interface. HQ values will be presented and discussed in the presentation.

Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

PubMed Central

Pyle, Louise C.; Ehrhardt, Annette; Mitchell, Lisa High; Fan, LiJuan; Ren, Aixia; Naren, Anjaparavanda P.; Li, Yao; Clancy, J. P.; Bolger, Graeme B.; Sorscher, Eric J.

2011-01-01

Modulator compounds intended to overcome disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) show significant promise in clinical testing for cystic fibrosis. However, the mechanism(s) of action underlying these compounds are not fully understood. Activation of CFTR ion transport requires PKA-regulated phosphorylation of the regulatory domain (R-D) and dimerization of the nucleotide binding domains. Using a newly developed assay, we evaluated nine compounds including both CFTR potentatiators and activators discovered via various high-throughput screening strategies to acutely augment CFTR activity. We found considerable differences in the effects on R-D phosphorylation. Some (including UCCF-152) stimulated robust phosphorylation, and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR activation by UCCF-152 and VRT-532 in Ussing chamber studies using two epithelial models, CFBE41o− and Fischer rat thyroid cells, expressing various CFTR forms. UCCF-152 activated wild-type-, G551D-, and rescued F508del-CFTR currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT-532 moderately activated CFTR short-circuit current and strongly potentiated forskolin-mediated current. Combined with the result that UCCF-152, but not VRT-532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR is not due to a pathway involving augmented R-D phosphorylation. This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. PMID:21724857

Inherited biallelic CSF3R mutations in severe congenital neutropenia.

PubMed

Triot, Alexa; Järvinen, Päivi M; Arostegui, Juan I; Murugan, Dhaarini; Kohistani, Naschla; Dapena Díaz, José Luis; Racek, Tomas; Puchałka, Jacek; Gertz, E Michael; Schäffer, Alejandro A; Kotlarz, Daniel; Pfeifer, Dietmar; Díaz de Heredia Rubio, Cristina; Ozdemir, Mehmet Akif; Patiroglu, Turkan; Karakukcu, Musa; Sánchez de Toledo Codina, José; Yagüe, Jordi; Touw, Ivo P; Unal, Ekrem; Klein, Christoph

2014-06-12

Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. © 2014 by The American Society of Hematology.

A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report.

PubMed

Tan, Hu; Wei, Xianda; Yang, Pu; Huang, Yanru; Li, Haoxian; Liang, Desheng; Wu, Lingqian

2017-07-01

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous hyperpigmentation, gastrointestinal (GI) hamartmatous polyps, and an increased risk of various malignancies. Pathogenic variants in the LKB1 tumor suppressor gene (also known as STK11) are the major cause of PJS. In this study, compound heterozygous variants of LKB1, c.890G > A/ c.1062C > G and del(exon1)/ c.1062C > G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G > A are pathogenic in these two PJS families rather than c.1062C > G. This finding would contribute to genetic counseling for individuals carrying the variant c.1062C > G with or without PJS phenotypes. Moreover, this finding reminds genetic counselors that it is necessary to reevaluate the pathogenicity of reported variants in a known Mendelian disorder in order to avoid a misleading decision.

Inherited biallelic CSF3R mutations in severe congenital neutropenia

PubMed Central

Triot, Alexa; Järvinen, Päivi M.; Arostegui, Juan I.; Murugan, Dhaarini; Kohistani, Naschla; Dapena Díaz, José Luis; Racek, Tomas; Puchałka, Jacek; Gertz, E. Michael; Schäffer, Alejandro A.; Kotlarz, Daniel; Pfeifer, Dietmar; Díaz de Heredia Rubio, Cristina; Ozdemir, Mehmet Akif; Patiroglu, Turkan; Karakukcu, Musa; Sánchez de Toledo Codina, José; Yagüe, Jordi; Touw, Ivo P.; Unal, Ekrem

2014-01-01

Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. PMID:24753537

El Efecto de la Educacion Bilingue Bicultural en los Autoconceptos y las Actitudes de Ninos Hispanicos

ERIC Educational Resources Information Center

Belendez, Pilar; Melendez, Sarah E.

1977-01-01

Written in Spanish, the article reports a study which compared the self concepts and attitudes toward their culture, the American culture, and school of Hispanic students in a maintenance and a transitional bilingual-bicultural program and in a monolingual school. (NQ)

Effect of widespread agricultural chemical use on butterfly diversity across Turkish provinces.

PubMed

Pekin, Burak K

2013-12-01

Although agricultural intensification is thought to pose a significant threat to species, little is known about its role in driving biodiversity loss at regional scales. I assessed the effects of a major component of agricultural intensification, agricultural chemical use, and land-cover and climatic variables on butterfly diversity across 81 provinces in Turkey, where agriculture is practiced extensively but with varying degrees of intensity. I determined butterfly species presence in each province from data on known butterfly distributions and calculated agricultural chemical use as the proportion of agricultural households that use chemical fertilizers and pesticides. I used constrained correspondence analyses and regression-based multimodel inference to determine the effect of environmental variables on species composition and richness, respectively. The variation in butterfly species composition across the provinces was largely explained (78%) by the combination of agricultural chemical use, particularly pesticides, and climatic and land-cover variables. Although overall butterfly richness was primarily explained by climatic and land-cover variables, such as the area of natural vegetation cover, threatened butterfly richness and the relative number of threatened butterfly species decreased substantially as the proportion of agricultural households using pesticides increased. These findings suggest that widespread use of agricultural chemicals, or other components of agricultural intensification that may be collinear with pesticide use, pose an imminent threat to the biodiversity of Turkey. Accordingly, policies that mitigate agricultural intensification and promote low-input farming practices are crucial for protecting threatened species from extinction in rapidly industrializing nations such as Turkey. Efectos del Uso Extensivo de Agroquímicos sobre la Diversidad de Mariposas en Provincias Turcas. © 2013 Society for Conservation Biology.

[In Process Citation].

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Vallejos-Rojas, Andrea; Jaramillo-Gallardo, Javiera; Salas Bravo, Carlos; Cano-Montoya, Johnattan; Celis-Morales, Carlos

2016-03-25

 Introducción: obesidad e inactividad física son importantes factores de riesgo para el desarrollo de hipertensión en adultos. No obstante, hay poca evidencia sobre el efecto de estos factores de riesgo en el desarrollo de hipertensión en población infantil. Objetivo: investigar la asociación del estado nutricional, niveles de actividad física y etnicidad con niveles de hipertensión en escolares entre 6 y 13 años de edad. Métodos: un total de 418 escolares de ascendencia étnica europea (n = 311) y mapuche (n = 107) fueron participantes de este estudio transversal. Se midió el peso, talla, índice de masa corporal (IMC) y presión arterial, utilizando protocolos estandarizados. Resultados: no se encontraron diferencias significativas en IMC, estado nutricional y presión arterial entre niños con ascendencia europea y mapuche. No obstante, la prevalencia de prehipertensión (21,3% vs. 11,1%) e hipertensión (28,9% vs. 18,6%) fue significativamente mayor en escolares mapuches en comparación con europeos, respectivamente. Escolares con ascendencia mapuche tienen un mayor riesgo de desarrollar prehipertensión o hipertensión que escolares con ascendencia europea (OR: 1,92 [1,19 a 3,06], p < 0,01). La prevalencia de hipertensión aumenta significativamente en ambos grupos étnicos con el incremento de IMC y bajos niveles de actividad física. Conclusiones: el riesgo de desarrollar prehipertensión o hipertensión es mayor en población infantil ascendiente de mapuches que ascendiente de europeos y este riesgo se ve acentuado con el incremento de obesidad y bajos niveles de actividad física.

Occurrence, fate and risk assessment of personal care products in river-groundwater interface.

PubMed

Serra-Roig, Maria Pau; Jurado, Anna; Díaz-Cruz, M Silvia; Vázquez-Suñé, Enric; Pujades, Estanislao; Barceló, Damià

2016-10-15

This work presents the occurrence and fate of selected personal care products (PCPs) in the urban river-groundwater interface. To this end, urban river and groundwater samples were collected in Sant Adrià del Besòs (NE of Spain) and a total of 16 PCPs were analyzed including benzophenone derivatives, camphor derivatives, p-aminobenzoic acid derivatives, triazoles and parabens in three different campaigns (from May 2010 to July 2014). These compounds reach the aquifer through the recharge of Besòs River that receives large amounts of effluents from waste water treatment plants. Results have shown that most of the compounds were not or barely detected (maximum concentrations around 200ng/L) in groundwater samples during the different sampling campaigns. Only two triazoles, namely benzotriazole (BZT) and methyl benzotriazol (MeBZT) were found at high concentrations in groundwater samples (maximum concentration around 2000ng/L). The fate of PCPs in the aquifer was assessed using mixing analysis considering the seasonal variability of the Besòs River. Overall, measured groundwater concentrations were significantly much lower than those estimated by the mixing of the river water. This observation suggested that most of the PCPs are naturally removed when river water infiltrates the aquifer. However, some compounds were more persistent in the aquifer. These compounds were in descending order: the triazoles BZT and MeBZT followed by the camphor derivative 4MBC and the paraben MePB. The measured concentrations allowed us to assess the environmental risk posed by the selected UV-filters and parabens in the river and groundwater samples. Hazard Quotients (HQs) for different aquatic species were calculated in order to characterize the ecotoxicity potential of the studied compounds in the river-groundwater interface. HQ values were always below 1 indicating that at the concentrations observed in the surface or aquifer water of Besòs River these compounds pose no risk to the selected aquatic organisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage

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

Wahba, Haytham M.; Stevenson, Michael J.; Mansour, Ahmed

2017-01-03

The organomercurial lyase MerB has the unique ability to cleave carbon–Hg bonds, and structural studies indicate that three residues in the active site (C96, D99, and C159 in E. coli MerB) play important roles in the carbon–Hg bond cleavage. However, the role of each residue in carbon–metal bond cleavage has not been well-defined. To do so, we have structurally and biophysically characterized the interaction of MerB with a series of organotin and organolead compounds. Studies with two known inhibitors of MerB, dimethyltin (DMT) and triethyltin (TET), reveal that they inhibit by different mechanisms. In both cases the initial binding ismore » to D99, but DMT subsequently binds to C96, which induces a conformation change in the active site. In contrast, diethyltin (DET) is a substrate for MerB and the SnIV product remains bound in the active site in a coordination similar to that of HgII following cleavage of organomercurial compounds. The results with analogous organolead compounds are similar in that trimethyllead (TML) is not cleaved and binds only to D99, whereas diethyllead (DEL) is a substrate and the PbIV product remains bound in the active site. Binding and cleavage is an exothermic reaction, while binding to D99 has negligible net heat flow. These results show that initial binding of organometallic compounds to MerB occurs at D99 followed, in some cases, by cleavage and loss of the organic moieties and binding of the metal ion product to C96, D99, and C159. The N-terminus of MerA is able to extract the bound PbVI but not the bound SnIV. These results suggest that MerB could be utilized for bioremediation applications, but certain organolead and organotin compounds may present an obstacle by inhibiting the enzyme.« less

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

PubMed

Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

2017-04-01

The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I-II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I-II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3-36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Volatile Compound Profiling by HS-SPME/GC-MS-FID of a Core Olive Cultivar Collection as a Tool for Aroma Improvement of Virgin Olive Oil.

PubMed

García-Vico, Lourdes; Belaj, Angjelina; Sánchez-Ortiz, Araceli; Martínez-Rivas, José M; Pérez, Ana G; Sanz, Carlos

2017-01-14

Virgin olive oil (VOO) is the only food product requiring official sensory analysis to be classified in commercial categories, in which the evaluation of the aroma plays a very important role. The selection of parents, with the aim of obtaining new cultivars with improved oil aroma, is of paramount importance in olive breeding programs. We have assessed the volatile fraction by headspace-solid-phase microextraction/gas chromatography-mass spectrometry-flame ionization detection (HS-SPME/GC-MS-FID) and the deduced aroma properties of VOO from a core set of olive cultivars (Core-36) which possesses most of the genetic diversity found in the World Olive Germplasm Collection (IFAPA Alameda del Obispo) located in Cordoba, Spain. The VOO volatile fractions of Core-36 cultivars display a high level of variability. It is mostly made of compounds produced from polyunsaturated fatty acids through the lipoxygenase pathway, which confirms to be a general characteristic of the olive species ( Olea europaea L.). The main group of volatile compounds in the oils was six straight-chain carbon compounds derived from linolenic acid, some of them being the main contributors to the aroma of the olive oils according to their odor activity values (OAV). The high level of variability found for the volatile fraction of the oils from Core-36 and, therefore, for the aroma odor notes, suggest that this core set may be a very useful tool for the choice of optimal parents in olive breeding programs in order to raise new cultivars with improved VOO aroma.

Whole-exome sequencing revealed two novel mutations in Usher syndrome.

PubMed

Koparir, Asuman; Karatas, Omer Faruk; Atayoglu, Ali Timucin; Yuksel, Bayram; Sagiroglu, Mahmut Samil; Seven, Mehmet; Ulucan, Hakan; Yuksel, Adnan; Ozen, Mustafa

2015-06-01

Usher syndrome is a clinically and genetically heterogeneous autosomal recessive inherited disorder accompanied by hearing loss and retinitis pigmentosa (RP). Since the associated genes are various and quite large, we utilized whole-exome sequencing (WES) as a diagnostic tool to identify the molecular basis of Usher syndrome. DNA from a 12-year-old male diagnosed with Usher syndrome was analyzed by WES. Mutations detected were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined by in silico analysis. A maternally inherited deleterious frameshift mutation, c.14439_14454del in exon 66 and a paternally inherited non-sense c.10830G>A stop-gain SNV in exon 55 of USH2A were found as two novel compound heterozygous mutations. Both of these mutations disrupt the C terminal of USH2A protein. As a result, WES revealed two novel compound heterozygous mutations in a Turkish USH2A patient. This approach gave us an opportunity to have an appropriate diagnosis and provide genetic counseling to the family within a reasonable time. Copyright © 2015 Elsevier B.V. All rights reserved.

N/Z effect on reaction mechanisms cross sections in the 78Kr + 40Ca and 86Kr + 48Ca collisions at 10A MeV

NASA Astrophysics Data System (ADS)

Gnoffo, B.; Pirrone, S.; Politi, G.; La Commara, M.; Wieleczko, J. P.; De Filippo, E.; Russotto, P.; Trimarchi, M.; Vigilante, M.; Ademard, G.; Auditore, L.; Beck, C.; Bercenau, I.; Bonnet, E.; Borderie, B.; Cardella, G.; Chibihi, A.; Colonna, M.; De Luca, S.; Dell'Aquila, D.; D'Onofrio, A.; Frankland, J. D.; Lanzalone, G.; Lautesse, P.; Lebhertz, D.; Le Neidre, N.; Lombardo, I.; Martorana, N. S.; Mazurek, N.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Piasecki, E.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Spadaccini, G.; Trifirò, A.; Verde, G.

2017-11-01

Nuclear reactions between medium-mass nuclei at low bombarding energy are characterized by the competition between binary and evaporation processes in the compound nucleus decay. A study of the influence of the neutron richness of the entrance channel on the decay paths of the compound nuclei formed in the 78Kr + 40Ca and 86Kr + 48Ca at 10MeV/A is presented. The experiment has been performed at Laboratori Nazionali del Sud by using the CHIMERA 4 π multidetector for charged particles. The kinematical characteristics of the two reactions support the conclusion of a production of the IMFs via long-lived system and the global features suggest a different competition among the various reaction channels. The cross sections of the mechanisms responsible for the fragments production have been extracted. Besides the results relative to the n-poor system are compared to those obtained at GANIL, performed at 5.5A MeV, in order to study the energy influence on the mechanisms.

GENETIC STRUCTURE OF TRIATOMA INFESTANS POPULATIONS IN RURAL COMMUNITIES OF SANTIAGO DEL ESTERO, NORTHERN ARGENTINA

PubMed Central

Marcet, PL; Mora, MS; Cutrera, AP; Jones, L; Gürtler, RE; Kitron, U; Dotson, EM

2008-01-01

To gain an understanding of the genetic structure and dispersal dynamics of T. infestans populations, we analyzed the multilocus genotype of 10 microsatellite loci for 352 T. infestans collected in 21 houses of 11 rural communities in October 2002. Genetic structure was analyzed at the community and house compound levels. Analysis revealed that vector control actions affected the genetic structure of T. infestans populations. Bug populations from communities under sustained vector control (core area) were highly structured and genetic differentiation between neighboring house compounds was significant. In contrast, bug populations from communities with sporadic vector control actions were more homogeneous and lacked defined genetic clusters. Genetic differentiation between population pairs did not fit a model of isolation by distance at the microgeographical level. Evidence consistent with flight or walking bug dispersal was detected within and among communities, dispersal was more female-biased in the core area and results suggested that houses received immigrants from more than one source. Putative sources and mechanisms of re-infestation are described. These data may be use to design improved vector control strategies PMID:18773972

Stable isotope hydrology in fractured and detritic aquifers at both sides of the South Atlantic Ocean: Mar del Plata (Argentina) and the Rawsonville and Sandspruit river catchment areas (South Africa)

NASA Astrophysics Data System (ADS)

Glok Galli, Melisa; Damons, Matthew E.; Siwawa, Sitembiso; Bocanegra, Emilia M.; Nel, Jacobus M.; Mazvimavi, Dominic; Martínez, Daniel E.

2017-01-01

The aim of this work is to characterize the isotope composition of water (2H and 18O) in order to establish the relationship between fractured and detritic aquifers in similar hydrological environments located at both sides of the Atlantic Ocean. The Mar del Plata zone, placed in the Argentine Buenos Aires province in South America, and the Rawsonville and Sandspruit river catchment areas, situated in the Western Cape province in South Africa were compared. Rainwater and groundwater samples from fractured and detritic aquifers were analyzed through laser spectroscopy. In both Argentina and South African study sites, stable isotopes data demonstrate an aquifers recharge source from rainfall. For the Mar del Plata region, two different groups of detritic aquifer's samples with distinct recharge processes can be identified due to the close relationship existing between the present hydrogeological environments, the aquifer's grain size sediments and the isotopes contents: one representing rapid infiltration in aquifer sediments of the creeks' palaeobeds and hills zones (sandy or silt sandy sediments) and the other with slow infiltration of evaporated water in plain zones with an aquitard behavior. In the last group, the evaporation process occurs previous infiltration or in the aquifer's non-saturated zone, because of the existence of very low topographic gradients and fine-grained sediments. The evaporation phenomenon is not evident in the Sandspruit river catchment site's detritic aquifer, because its sandy composition allows a faster infiltration rate than in the loess that compounds the Pampeano aquifer in the interfluves zones of the Argentinian study area.

[Deletion of a dynamic surface loop improves thermostability of (R)-selective amine transaminase from Aspergillus terreus].

PubMed

Xie, Dongfang; Lv, Changjiang; Fang, Hui; Yang, Weikang; Hu, Sheng; Zhao, Weirui; Huang, Jun; Mei, Lehe

2017-12-25

Chiral amines are important building blocks for the synthesis of pharmaceutical products and fine chemicals. Highly stereoselective synthesis of chiral amines compounds through asymmetric amination has attracted more and more attention. ω-transaminases (ω-TAs) are a promising class of natural biocatalysts which provide an efficient and environment-friendly access to production of chiral amines with stringent enantioselectivity and excellent catalytic efficiency. Compared with (S)-ω-TA, the research focused on (R)-ω-TA was relatively less. However, increasing demand for chiral (R)-amines as pharmaceutical intermediates has rendered industrial applications of (R)-ω-TA more attractive. Improving the thermostability of (R)-ω-TA with potential biotechnological application will facilitate the preparation of chiral amines. In this study, the dynamic surface loop with higher B-factor from Aspergillus terreus (R)-ω-TA was predicted by two computer softwares (PyMOL and YASARA). Then mutant enzymes were obtained by deleting amino acid residues of a dynamic surface loop using site-directed mutagenesis. The results showed that the best two mutants R131del and P132-E133del improved thermostability by 2.6 ℃ and 0.9 ℃ in T₅₀¹⁰ (41.1 ℃ and 39.4 ℃, respectively), and 2.2-fold and 1.5-fold in half-life (t1/2) at 40 ℃ (15.0 min and 10.0 min, respectively), compared to that of wild type. Furtherly, the thermostability mechanism of the mutant enzymes was investigated by molecular dynamics (MD) simulation and intermolecular interaction analysis. R131del in the loop region has lower root mean square fluctuation (RMSF) than the wild type at 400 K for 10 ns, and mutant enzyme P132-E133del increases four hydrogen bonds in the loop region. In this study, we obtain two stability-increased mutants of (R)-ω-TA from A. terreus by deleting its dynamic surface loop and also provide methodological guidance for the use of rational design to enhance the thermal stability of other enzymes.

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

PubMed

Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

2017-10-01

During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel Variations of FANCA Gene Provokes Fanconi Anemia: Molecular Diagnosis in a Special Chinese Family.

PubMed

Li, Niu; Song, Aiyun; Ding, Lixia; Zhu, Hua; Li, Guoqiang; Miao, Yan; Wang, Jian; Li, Benshang; Chen, Jing

2018-07-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder with highly variable clinical manifestations and an incidence of ∼1 to 5 in 1 million births. To date, 15 bona fide FA genes have been reported to be responsible for the known FA complementation groups and the FANCA gene accounts for almost 60%. In the present study, we report a special Chinese family, which has 2 children with classic FA characteristics. Via 2-step analysis of the whole-exome sequencing data and verification using multiplex ligation-dependent probe amplification test, one child was found to have a novel compound heterozygous mutation of a splicing variant (c.1471-1G>A) and a large intragenic deletion (exons 23-30 del) of the FANCA gene. The other child had the same splicing variant and another novel large deletion (exons 1-18 del) in the FANCA gene. Clone sequencing showed the c.1471-1G>A variant generate an altered transcript with 1 cryptic splice site in intron 15, resulting in a premature termination codon (p.Val490HisfsX6). This study not only shows the complexity of FA molecular diagnosis via comprehensively studying the FA pathogenic genes and the mutational spectrum, but also has significant reference value for the future molecular diagnosis of FA.

[Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases].

PubMed

Enacán, Rosa E; Masnata, María E; Belforte, Fiorella; Papendieck, Patricia; Olcese, María C; Siffo, Sofía; Gruñeiro-Papendieck, Laura; Targovnik, Héctor; Rivolta, Carina M; Chiesa, Ana E

2017-06-01

Congenital hypothyroidism affects 1:2000-3000 newborns detected by neonatal screening programs. Dual oxidases, DUOX1 and 2, generate hydrogen peroxide needed for the thyroid hormone synthesis. Hipotiroidismo congénito transitorio por defectos bialélicos del gen DUOX2. Dos casos clínicos Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases Mutations in the DUOX2 gene have been described in transient and permanent congenital hypothyroidism. Two brothers with congenital hypothyroidism detected by neonatal screening with eutopic gland and elevated thyroglobulin are described. They were treated with levothyroxine until it could be suspended in both during childhood, assuming the picture as transient. Organification disorder was confirmed. Both patients were compounds heterozygous for a mutation in exon 9 of the paternal allele (c.1057_1058delTT, p.F353PfsX36 or p.F353fsX388) and in exon 11 of the maternal allele (c.1271T > G, p.Y425X) of DUOX2 gene. Our finding confirms that the magnitude of the defect of DUOX2 is not related to the number of inactivated alleles, suggesting compensatory mechanisms in the peroxide supply. Sociedad Argentina de Pediatría.

A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family.

PubMed

Batissoco, A C; Auricchio, M T B M; Kimura, L; Tabith-Junior, A; Mingroni-Netto, R C

2009-02-01

Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries. We report here on a novel point mutation in GJB2, p.L76P (c.227C>T), in compound heterozygosity with a c.35delG mutation, in two Brazilian sibs, one presenting mild and the other profound nonsyndromic neurosensorial hearing impairment. Their father, who carried a wild-type allele and a p.L76P mutation, had normal hearing. The mutation leads to the substitution of leucine (L) by proline (P) at residue 76, an evolutionarily conserved position in Cx26 as well as in other connexins. This mutation is predicted to affect the first extracellular domain (EC1) or the second transmembrane domain (TM2). EC1 is important for connexon-connexon interaction and for the control of channel voltage gating. The segregation of the c.227C>T (p.L76P) mutation together with c.35delG in this family indicates a recessive mode of inheritance. The association between the p.L76P mutation and hearing impairment is further supported by its absence in a normal hearing control group of 100 individuals, 50 European-Brazilians and 50 African-Brazilians.

Isolated Nonvisualization of the Fetal Gallbladder Should Be Considered for the Prenatal Diagnosis of Cystic Fibrosis.

PubMed

Bergougnoux, Anne; Jouannic, Jean-Marie; Verneau, Fanny; Bienvenu, Thierry; Gaitch, Natacha; Raynal, Caroline; Girodon, Emmanuelle

2018-06-19

Cystic fibrosis (CF) can be revealed during fetal life by diverse ultrasound digestive abnormalities (USDA) such as fetal echogenic bowel or fetal intestinal loop dilatation, nonvisualization of the fetal gallbladder (NVFGB) being rarely observed in isolation. Only 6 cases of CF revealed by isolated NVFGB have been reported so far in the literature. Furthermore, recent studies suggested that this sign is of poor predictive value for CF. We report on the results of a 6-year French tricenter study on 1,124 cases of fetal USDA for whom a comprehensive molecular study was performed for CF. Among the 37 CF fetuses, 5 (13.5%) presented with isolated NVFGB at ultrasound (US) examination at 24-31 weeks of gestation. This sign was more frequently observed in CF fetuses than in non-CF fetuses, with a likelihood ratio of 2.7. The genotypes included three c.1521_1523del (F508del) homozygous cases and two compound heterozygous cases for a frequent and a rare CF-causing variant. These observations highlight the importance to report on the presence and aspect of the fetal gallbladder at the second trimester US scan and to consider prenatal CFTR molecular analysis in cases of isolated NVFGB. © 2018 S. Karger AG, Basel.

Biallelic mutations in GPD1 gene in a Chinese boy mainly presented with obesity, insulin resistance, fatty liver, and short stature.

PubMed

Li, Niu; Chang, Guoying; Xu, Yufei; Ding, Yu; Li, Guoqiang; Yu, Tingting; Yao, Ruen; Li, Juan; Shen, Yiping; Wang, Xiumin; Wang, Jian

2017-12-01

Biallelic mutations in the GPD1 gene cause a rare autosomal recessive inherited disease known as transient infantile hypertriglyceridemia (OMIM #614480). To date, only five pathogenic variants have been reported in 15 patients from three studies. The clinical symptoms of the affected individuals present a certain degree of heterogeneity. Here, we describe a chinese adolescent patient who mainly presented with obesity, insulin resistance, fatty liver, and short stature. Targeted next-generation sequencing revealed a novel compound heterozygous variant in GPD1 gene (c.220-2A>G and c.820G>A; p.Ala274Thr). In vitro studies demonstrated that the Ala274Thr variant induced a decrease in GPD1 protein expression. Further in vitro investigation of the splicing pattern in a minigene construct in HEK293 cells showed that the c.220-2A>G variant generated an altered transcript with one cryptic splice site in exon 3, resulting in the loss of 69 bases in exon 3 (c.220_288del, p.74_96del). This is the first report involving an Asian who harbored GPD1 mutations. Our work not only expands the mutant spectrum of the GPD1 gene but also provides new insights on its resulting phenotype. © 2017 Wiley Periodicals, Inc.

Incentivizing Monitoring and Compliance in Trophy Hunting

PubMed Central

BUNNEFELD, NILS; EDWARDS, CHARLES T T; ATICKEM, ANAGAW; HAILU, FETENE; MILNER-GULLAND, E J

2014-01-01

Conservation scientists are increasingly focusing on the drivers of human behavior and on the implications of various sources of uncertainty for management decision making. Trophy hunting has been suggested as a conservation tool because it gives economic value to wildlife, but recent examples show that overharvesting is a substantial problem and that data limitations are rife. We use a case study of trophy hunting of an endangered antelope, the mountain nyala (Tragelaphus buxtoni), to explore how uncertainties generated by population monitoring and poaching interact with decision making by 2 key stakeholders: the safari companies and the government. We built a management strategy evaluation model that encompasses the population dynamics of mountain nyala, a monitoring model, and a company decision making model. We investigated scenarios of investment into antipoaching and monitoring by governments and safari companies. Harvest strategy was robust to the uncertainty in the population estimates obtained from monitoring, but poaching had a much stronger effect on quota and sustainability. Hence, reducing poaching is in the interests of companies wishing to increase the profitability of their enterprises, for example by engaging community members as game scouts. There is a threshold level of uncertainty in the population estimates beyond which the year-to-year variation in the trophy quota prevented planning by the safari companies. This suggests a role for government in ensuring that a baseline level of population monitoring is carried out such that this level is not exceeded. Our results illustrate the importance of considering the incentives of multiple stakeholders when designing frameworks for resource use and when designing management frameworks to address the particular sources of uncertainty that affect system sustainability most heavily. Incentivando el Monitoreo y el Cumplimiento en la Caza de Trofeos Resumen Científicos conservacionistas cada vez se enfocan más en los conductores del comportamiento humano y en las implicaciones de varias fuentes de incertidumbre en la toma de decisiones de manejo. La cacería de trofeos ha sido sugerida como una herramienta de conservación porque le otorga valor económico a la vida silvestre, pero ejemplos recientes muestran que la sobrecolecta es un problema sustancial y que las limitaciones de datos son abundantes. Usamos el estudio de caso de la cacería de trofeos de un antílope en peligro, el nyala de las montañas (Tragelaphus buxtoni), para explorar como las incertidumbres generadas por el monitoreo de poblaciones y el tráfico de especies interactúan con la toma de decisiones de 2 actores clave: las compañías de safari y el gobierno. Construimos un modelo de evaluación de estrategia de manejo que incluye la dinámica poblacional del nyala de las montañas, un modelo de monitoreo y un modelo de toma de decisiones de una compañía. Investigamos escenarios de inversión en el combate del tráfico de especies y el monitoreo por el gobierno y las compañías de safari. La estrategia de colecta fue robusta hacia la incertidumbre en los estimados de población obtenidos del monitoreo, pero el tráfico de especies tuvo un efecto más fuerte sobre la cuota y la sustentabilidad; por esto, reducir el tráfico de especies está dentro de los intereses de compañías que desean incrementar la rentabilidad de las empresas, por ejemplo al hacer participar a los miembros de la comunidad como guías de caza. Hay un nivel umbral de incertidumbre en los estimados de población más allá del cual la variación anual en la cuota de trofeos previene la planeación por parte de las compañías de safari. Esto sugiere un papel para el gobierno asegurando que un nivel base de monitoreo de población se lleve a cabo para que este nivel no sea excedido. Nuestros resultados ilustran la importancia de considerar los incentivos de partes interesadas múltiples al designar marcos de trabajo para el uso de recursos y que al designar marcos de trabajo de manejo dirigirse a las fuentes particulares de incertidumbre que afecten más al sistema de sustentabilidad. PMID:24001054

The impact of the use of different types of gloves and bare hands for preparation of clean surgical instruments.

PubMed

Bruna, Camila Quartim de Moraes; Souza, Rafael Queiroz de; Massaia, Irineu Francisco Silva; Cruz, Áurea Silveira; Graziano, Kazuko Uchikawa

2016-10-10

to determine if there are differences on the safety of the preparation of clean surgical instruments using different types of gloves and bare hands and evaluate the microbiological load of these preparations without gloves. laboratory procedure with a pragmatic approach, in which the samples were handled with different types of gloves and bare hands. In addition, cytotoxicity assays were carried out by means of the agar diffusion method. Further samples were subjected to microbiological analysis after being handled without gloves. none of the samples showed cytotoxic effect. All microbiological cultures showed growth of microorganisms, but no microorganism has been recovered after autoclaving. there were no differences in the cytotoxic responses regarding the use of different types of gloves and bare hands in the handling of clean surgical instruments, which could entail iatrogenic risk. It is noteworthy that the use of gloves involves increase in the costs of process and waste generation, and the potential allergenic risk to latex. determinar se existe diferenças na segurança do preparo de instrumentais cirúrgicos relacionada ao uso de distintos tipos de luvas e das mãos nuas no preparo, e avaliar a carga microbiológica destes preparados sem luvas. experimento laboratorial com abordagem pragmática, onde amostras foram manipuladas com diferentes tipos de luvas e com as mãos nuas, elaborado teste de citotoxicidade por meio da difusão em ágar. Outras Amostras sofreram análise microbiológica após serem manipuladas sem luvas. nenhuma das amostras apresentou efeito citotóxico. Todas as culturas microbiológicas apresentaram crescimento de microrganismos, embora nenhum microrganismo tenha sido recuperado após a autoclavação. não houve diferenças nas respostas citotóxicas relacionadas ao uso de diferentes tipos de luvas e das mãos nuas na manipulação do instrumental cirúrgico limpo que sinalizasse risco de iatrogenia. Ressalta-se que o uso de luvas implica em aumento dos custos do processo e da geração de resíduos, além do potencial risco alergênico ao látex. determinar si existen diferencias en la seguridad de la preparación del instrumental quirúrgico relacionadas con el uso de diferentes tipos de guantes y de las manos desnudas y evaluar la carga microbiológica de estos preparados sin guantes. experimento de laboratorio con enfoque pragmático, en el que las muestras fueron manejadas con diferentes tipos de guantes y las manos desnudas. Además, un ensayo de citotoxicidad se llevó a cabo mediante el método de difusión en agar. Otras muestras fueron sometidas a análisis microbiológico después de haber sido manipuladas sin guantes. ninguna de las muestras presentó efecto citotóxico. Todos los cultivos microbiológicos mostraron crecimiento de microorganismos, pero ningún microorganismo ha sido recuperado después de la esterilización en autoclave. no hubo diferencias en las respuestas citotóxicas con respecto al uso de diferentes tipos de guantes y de las manos desnudas en el manejo del instrumental quirúrgico limpio, lo que podría conllevar riesgo de yatrogenia. Es de destacar que el uso de guantes implica un aumento de los costos del proceso y la generación de residuos, además del potencial riesgo alergénico al látex.

Evaluation of the telephone intervention in the promotion of diabetes self-care: a randomized clinical trial.

PubMed

Fernandes, Bárbara Sgarbi Morgan; Reis, Ilka Afonso; Torres, Heloisa de Carvalho

2016-08-29

to evaluate the effectiveness of the telephone intervention for promoting self-care related to physical activity and following a diet plan in users with diabetes, compared to conventional monitoring of users over a six-month period. this was a randomized clinical trial, which included 210 users with diabetes, linked to eight Primary Health Units of Belo Horizonte, Minas Gerais. The experimental group (104 members) received six telephone interventions over the six-month monitoring; the control group (106 members) received conventional monitoring. To evaluate the self-care practices related to physical activity and following a healthy eating plan, in both groups, the self-care questionnaire was applied before the intervention and at three and six months after its start. the mean effect of self-care scores in the experimental group was 1.03 to 1.78 higher than the control group, with progressive and significant improvement (p<0.001). the results indicate that the telephone intervention had a beneficial effect on diabetes self-care. The primary identifier of the clinical trials registry was: RBR-8wx7qb. avaliar a efetividade da intervenção telefônica na promoção do autocuidado relacionado à atividade física e ao seguimento de um plano alimentar, em usuários com diabetes, quando comparada ao acompanhamento convencional dos usuários, durante o período de seis meses. trata-se de um ensaio clínico randomizado, no qual participaram 210 usuários com diabetes, vinculados a oito Unidades Básicas de Saúde de Belo Horizonte, Minas Gerais. O grupo-experimental (104 usuários) recebeu seis intervenções telefônicas em seis meses de acompanhamento; o grupo-controle (106 usuários) recebeu acompanhamento convencional. Para avaliar as práticas de autocuidado, relacionada à atividade física e ao seguimento do plano alimentar saudável, em ambos os grupos, aplicou-se o questionário de autocuidado antes das intervenções, três e seis meses após o seu início. o efeito médio dos escores de autocuidado no grupo-experimental a pontuação foi de 1,03 a 1,78 maior do que o grupo-controle, apresentando melhora progressiva e significativa (valor-p<0,001). os resultados apontam que a intervenção telefônica tem efeito benéfico sobre o autocuidado em diabetes. O registro clínico obteve identificador primário: RBR-8wx7qb. evaluar la efectividad de la intervención telefónica en la promoción del autocuidado relacionado a la actividad física y al seguimiento de un plan alimentario, en usuarios con diabetes, cuando comparada al acompañamiento convencional de los usuarios, durante el período de seis meses. se trata de un ensayo clínico aleatorio, en el cual participaron 210 usuarios con diabetes, vinculados a ocho Unidades Básicas de la Salud de Belo Horizonte, Minas Gerais. El grupo experimental (104 usuarios) recibió seis intervenciones telefónicas en seis meses de acompañamiento; el grupo control (106 usuarios) recibió acompañamiento convencional. Para evaluar las prácticas de autocuidado, relacionadas a la actividad física y al seguimiento del plan alimentario saludable, en los dos grupos, se aplicó el cuestionario de autocuidado antes de las intervenciones, tres y seis meses después de su inicio. el efecto promedio de los puntajes de autocuidado en el grupo experimental fue de 1,03 a 1,78 mayor que el grupo control, presentando mejoría progresiva y significativa (valor-p<0,001). los resultados apuntan que la intervención telefónica tiene efecto benéfico sobre el autocuidado en diabetes. El registro clínico obtuvo identificador primario: RBR-8wx7qb.

Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia.

PubMed

Nemoto, Michiko; Hattori, Hiroyoshi; Maeda, Naoko; Akita, Nobuhiro; Muramatsu, Hideki; Moritani, Suzuko; Kawasaki, Tomonori; Maejima, Masami; Ode, Hirotaka; Hachiya, Atsuko; Sugiura, Wataru; Yokomaku, Yoshiyuki; Horibe, Keizo; Iwatani, Yasumasa

2018-05-03

Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4 + T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings' genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient's T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients.

Targeted exome sequencing identifies novel compound heterozygous mutations in P3H1 in a fetus with osteogenesis imperfecta type VIII.

PubMed

Huang, Yanru; Mei, Libin; Lv, Weigang; Li, Haoxian; Zhang, Rui; Pan, Qian; Tan, Hu; Guo, Jing; Luo, Xiaomei; Chen, Chen; Liang, Desheng; Wu, Lingqian

2017-01-01

Osteogenesis imperfecta (OI) is a highly clinically and genetically heterogeneous group of disorders. It is difficult to identify severe OI in the perinatal period. Here, a Chinese woman with a suspected history of fetal OI was referred to our institution at 19weeks of gestation, due to ultrasound inspection during antenatal screening, which revealed bulbous metaphyses, short humeri, and short thick bent femora in the fetus. Using targeted exome sequencing of 248 genes known to be involved in skeletal system diseases, we identified novel compound heterozygous mutation in the P3H1 gene in the fetus with OI type VIII: c.105_120del (p.D36Rfs*16) and c.2164C>T (p.Q722*). These two mutations were inherited from the father and mother, respectively. The mRNA level of P3H1 wasn't changed suggested that mRNA with this mutation escaped from nonsense-mediated RNA decay. Besides, the level of P3H1 was absence while the CRTAP was mildly decreased. In conclusion, our findings imply this novel compound heterozygous mutation as the molecular pathogenetic in a Chinese fetus with OI type VIII, and demonstrate that targeted next-generation sequencing (NGS) is an accurate, rapid, and cost-effective method in the genetic diagnosis of fetal skeletal dysplasia with genetic and clinical heterogeneity, especially for autosomal recessive skeletal disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Parent-child conflict and psychological maladjustment: a mediational analysis with reciprocal filial belief and perceived threat.

PubMed

Yeh, Kuang-Hui; Tsao, Wei-Chun; Chen, Wei-Wen

2010-04-01

Empirical research has shown that parent-child conflict is positively related to poor adjustment in adolescents; however, the underlying processes have not been adequately examined. To explore the possible mediating pathways, reciprocal filial belief and perceived threat were chosen to represent two likely mechanisms accounting for how parent-child conflict harms adolescents' perceptions of their relationship with their parents and their self-perceptions within their cognitive-appraisal framework. The former operates by attenuating children's affection towards their parents and the latter by lowering their self-perceptions. This study also distinguishes internalizing from externalizing problems in order to examine whether lower reciprocal filial belief more strongly mediates the relation between conflict with parents and adolescents' externalizing problems and whether perceived threat more strongly mediates the relation between conflict with parents and adolescents' internalizing problems. Hypotheses are as follows: (1) the more parent-child conflict adolescents report, the less reciprocal filial belief they recognize, which, in turn, leads to more maladjustments, especially externalizing ones; (2) the more parent-child conflicts adolescents report, the more threat they perceive, which, in turn, leads to more maladjustments, especially internalizing ones. Participants consisted of 603 Taiwanese adolescents (226 males and 377 females) aged 15 to 19 (average age = 16.95; SD = 0.78). Structural equation modelling analyses confirmed the hypotheses. However, the three direct effects of conflict on internalizing problems, aggression, and deviant behaviour were still significant. In addition, a greater effect of the paternal than the maternal role on the link between conflict and attenuated reciprocal filial belief, and between perceived threat and internalizing problems, was identified. Implications for understanding the mediation processes responsible for all indirect effects, even the subsidiary ones, and the greater impact of conflict with the father than with the mother are discussed. Limitations of the study and considerations for future research are also addressed. La recherche empirique a indiqué que le conflit parent-enfant est positivement lié à une faible adaptation chez les adolescents; cependant, les processus sous-jacents n'ont pas été adéquatement examinés. Pour explorer les trajectoires de médiation possibles, la croyance filiale réciproque et la menace perçue ont été sélectionnées afin de représenter deux méchanismes plausiblement responsables de comment le conflit parent-enfant nuit aux peceptions des adolescents de leur relation avec les parents ainsi que de leurs auto-perceptions dans le cadre de leur évaluation cognitive. Le premier fonctionne en atténuant l'affection des enfants envers leurs parents et le dernier fonctionne en diminuant leurs auto-perceptions. Cette étude distingue aussi les problèmes internalisés de ceux qui sont externalisés dans le but d'examiner si la plus faible croyance de filiation réciproque médie fortement la relation entre le conflit avec les parents et les problèmes externalisés des adolescents et si la menace perçue médie plus fortement la relation entre le conflit avec les parents et les problèmes internalisés des adolescents. Les hypothèses sont les suivantes: (1) plus il y a de conflit parent-enfant rapporté par les adolescents, moins il y aura de croyance filiale réciproque reconnue par les adolescents qui, en revanche, mènera à plus de mésadaptation surtout externalisée. L'échantillon incluait 603 participants (226 mâles et 377 femelles) âgés entre 15 et 19 ans (âge moyen = 16.95; SD = 0.78). Une analyse de modélisation par équation structurelle a confirmé les hypotheses. Cependant, les trois effets directs du conflit sur les problèmes internalisés, sur l'agression et sur le comportement déviant étaient toujours significatifs. De plus, nous avons observé un plus grand effet du rôle paternel plus que maternel sur le lien entre le conflit et la croyance filiale réciproque atténuée ainsi qu'entre la menace perçue et les problèmes internalisés. Les implications pour la compréhension des processus de médiation responsables pour tous les effets indirects, même ceux qui sont accessoires, et le plus grand impact du conflit avec le père plus qu'avec la mère sont discutés. Les limites de l'étude et les considérations pour la recherche future sont aussi abordées. La investigación empírica ha demostrado que el conflicto entre padres e hijos está positivamente relacionado con pobre ajuste en adolescentes; no obstante, el proceso subyacente no ha sido examinado adecuadamente. Para explorar posibles caminos, se eligieron la creencia filial recíproca y la amenaza percibida con el objetivo de representar dos posibles mecanismos explicativos de cómo el conflicto padres-hijos daña la percepción de los adolescentes de su relación con los padres y su auto-percepción dentro de su marco de valoración cognitiva. El primero actúa atenuando el afecto de los hijos hacia los padres y el último bajando su auto-percepción. Este estudio también distingue los problemas interiorizados de los exteriorizados para examinar si la baja creencia filial recíproca es un mediador más fuerte de la relación entre el conflicto con los padres y los problemas exteriorizados de los adolescentes y si la amenaza percibida es un mediador más fuerte de la relación entre el conflicto con los padres y los problemas interiorizados de los adolescentes. Se han planteado las siguientes hipótesis: (1) cuanto más conflicto entre padres e hijos refieran los adolescentes, menor será el reconocimiento de la creencia filial recíproca, lo cual llevará a inadaptación, sobre todo, exteriorizada; (2) cuanto más conflicto entre padres e hijos refieran los adolescentes, mayor será la amenaza percibida, lo cual llevará a mayor inadaptación, sobre todo interiorizada. La muestra consistió de 603 adolescentes taiwaneses (226 chicos y 377 chicas) entre 15 y 19 años de edad (media edad = 16.95; DT = 0.78). Los análisis de los modelos de ecuaciones estructurales confirmaron las hipótesis. Sin embargo, los tres efectos directos de los conflictos en la internalización de los problemas, agresión y comportamiento anormal seguían siendo significativos. Además, se identificó un efecto mayor del rol paternal en comparación con el rol maternal en la relación entre conflicto y la creencia filial reciproca atenuada y entre la amenaza percibida y la internalización de los problemas. Se discuten las implicaciones para la comprensión del proceso mediador responsable de todos los efectos indirectos, incluso los subsidiarios, y el mayor impacto del conflicto con los padres que con las madres. Igualmente, se discuten las limitaciones del estudio y las consideraciones para la investigación futura.

[In Process Citation].

PubMed

Fófano do Lago, Márcia; Chaia Kaippert, Vanessa; Lopes Souto, Débora; Lopes Rosado, Eliane

2016-03-25

Introducción: el tipo de ácido graso de la dieta presenta diferentes efectos sobre la obesidad y sus complicaciones, pero estos efectos pueden verse influenciados por los genes y sus polimorfismos, tales como los receptores activados por el proliferador de los peroxisomas isoforma γ2 (PPARγ2). Además, no está claro si el grado de insaturación de los lípidos posee diferentes efectos en el metabolismo de los lípidos y de la glucosa y, particularmente, en la pérdida de peso. Objetivos: evaluar la influencia de dietas ricas en ácidos grasos poliinsaturados (AGPI) y monoinsaturados (AGMI) en las variables antropométricas y bioquímicas en el peso corporal y el perfil glucémico y lipémico en mujeres obesas con el genotipo Pro12Pro en el gen PPARγ2. Métodos: dieciocho mujeres obesas con genotipo Pro12Pro fueron distribuidas aleatoriamente para una de las dietas, rica en AGPI (n = 8) o AGMI (n = 10). Las variables antropométricas (índice de masa corporal [IMC] y circunferencia de la cintura) y bioquímicas (glucosa, insulina, HOMA-IR, colesterol total, LDL-colesterol, HDL colesterol y triglicéridos) fueron evaluadas antes y después de un periodo de 45 días. Resultados: las variables antropométricas y bioquímicas fueron similares entre los grupos antes y después de la intervención (p > 0,05). El IMC disminuyó después de la ingesta de AGPI (p = 0,01), probablemente debido al menor contenido de lípidos. El AGMI redujo la glucosa (p = 0,03), insulina (p = 0,03) y HOMA-IR (p = 0,02). Conclusión: los AGMI fueron más eficientes para reducir la resistencia a la insulina en mujeres obesas con el genotipo Pro12Pro en el gen PPARγ2, aunque las mujeres presentaran una elevada ingesta de lípidos totales y ácidos grasos saturados.

77 FR 31032 - National Institute on Aging; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... applications. Place: Marina del Rey Hotel, 13534 Bali Way, Marina del Rey, CA 90292. Contact Person: Bita... applications. Place: Marina del Rey Hotel, 13534 Bali Way, Marina del Rey, CA 90292. Contact Person: Ramesh... and evaluate grant applications. Place: Marina del Rey Hotel, 13534 Bali Way, Marina del Rey, CA 90292...

Isoflavanones from the allelopathic aqueous root exudate of Desmodium uncinatum.

PubMed

Tsanuo, Muniru K; Hassanali, Ahmed; Hooper, Antony M; Khan, Zeyaur; Kaberia, Festus; Pickett, John A; Wadhams, Lester J

2003-09-01

Three isoflavanones, 5,7,2',4'-tetrahydroxy-6-(3-methylbut-2-enyl)isoflavanone (1), 4",5"-dihydro-5,2',4'-trihydroxy-5"-isopropenylfurano-(2",3";7,6)-isoflavanone (2) and 4",5"-dihydro-2'-methoxy-5,4'-dihydroxy-5"-isopropenylfurano-(2",3";7,6)-isoflavanone (3) and a previously known isoflavone 5,7,4'-trihydroxyisoflavone [genistein (4)] were isolated and characterised spectroscopically from the root exudate of the legume Desmodium uncinatum (Jacq.) DC. We propose the names uncinanone A, B, and C for compounds 1, 2 and 3, respectively. Isolated fractions containing uncinanone B (2) induced germination of seeds from the parasitic weed Striga hermonthica (Del.) Benth. and fractions containing uncinanone C (3) moderately inhibited radical growth, the first example of a newly identified potential allelopathic mechanism to prevent S. hermonthica parasitism.

Biallelic UNC80 mutations caused infantile hypotonia with psychomotor retardation and characteristic facies 2 in two Chinese patients with variable phenotypes.

PubMed

He, Yunjuan; Ji, Xing; Yan, Hui; Ye, Xiantao; Liu, Yu; Wei, Wei; Xiao, Bing; Sun, Yu

2018-06-20

Biallelic UNC80 mutations cause infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2), which is characterized by hypotonia, developmental delay (DD)/intellectual disability (ID), intrauterine growth retardation, postnatal growth retardation and characteristic facial features. We report two unrelated Chinese patients with compound heterozygous UNC80 mutations inherited from their parents, as identified by whole-exome sequencing (WES). Mutations c.3719G>A (p.W1240*)/c.4926_4937del (p.N1643_L1646del) and c.4963C>T (p.R1655C)/c.8385C>G (p.Y2795*) were identified in patient 1 and patient 2, respectively. Although both patients presented with DD/ID and hypotonia, different manifestations also occurred. Patient 1 presented with infantile hypotonia, epilepsy and hyperactivity without growth retardation, whereas patient 2 presented with persistent hypotonia, growth retardation and self-injury without epilepsy. Furthermore, we herein summarize the genotypes and phenotypes of patients with UNC80 mutations reported in the literature, revealing that IHPRF2 is a phenotypically heterogeneous disease. Common facial dysmorphisms include a thin upper lip, a tented upper lip, a triangular face, strabismus and microcephaly. To some extent, the manifestations of IHPRF2 mimic those of Angelman syndrome (AS)-like syndromes. Copyright © 2018 Elsevier B.V. All rights reserved.

Discovery and characterization of a novel irreversible EGFR mutants selective and potent kinase inhibitor CHMFL-EGFR-26 with a distinct binding mode

PubMed Central

Chen, Cheng; Yu, Kailin; Zou, Fengming; Wang, Wenchao; Wang, Wei; Wu, Jiaxin; Liu, Juan; Wang, Beilei; Wang, Li; Ren, Tao; Zhang, Shanchun; Yun, Cai-Hong; Liu, Jing; Liu, Qingsong

2017-01-01

EGFR T790M mutation accounts for about 40-55% drug resistance for the first generation EGFR kinase inhibitors in the NSCLC. Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M. It displayed proper selectivity window between the EGFR mutants and the wide-type. CHMFL-EGFR-26 exhibited good selectivity profile among 468 kinases/mutants tested (S score (1)=0.02). In addition, X-ray crystallography revealed a distinct “DFG-in” and “cHelix-out” inactive binding mode between CHMFL-EGFR-26 and EGFR T790M protein. The compound showed highly potent anti-proliferative efficacy against EGFR mutant but not wide-type NSCLC cell lines through effective inhibition of the EGFR mediated signaling pathway, induction of apoptosis and arresting of cell cycle progression. CHMFL-EGFR-26 bore acceptable pharmacokinetic properties and demonstrated dose-dependent tumor growth suppression in the H1975 (EGFR L858R/T790M) and PC-9 (EGFR del19) inoculated xenograft mouse models. Currently CHMFL-EGFR-26 is undergoing extensive pre-clinical evaluation for the clinical trial purpose. PMID:28407693

Identifying mutations in Tunisian families with retinal dystrophy.

PubMed

Habibi, Imen; Chebil, Ahmed; Falfoul, Yosra; Allaman-Pillet, Nathalie; Kort, Fedra; Schorderet, Daniel F; El Matri, Leila

2016-11-22

Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population.

High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.

PubMed

Islam, Md Tarikul; Sarkar, Suprovath Kumar; Sultana, Nusrat; Begum, Mst Noorjahan; Bhuyan, Golam Sarower; Talukder, Shezote; Muraduzzaman, A K M; Alauddin, Md; Islam, Mohammad Sazzadul; Biswas, Pritha Promita; Biswas, Aparna; Qadri, Syeda Kashfi; Shirin, Tahmina; Banu, Bilquis; Sadya, Salma; Hussain, Manzoor; Sarwardi, Golam; Khan, Waqar Ahmed; Mannan, Mohammad Abdul; Shekhar, Hossain Uddin; Chowdhury, Emran Kabir; Sajib, Abu Ashfaqur; Akhteruzzaman, Sharif; Qadri, Syed Saleheen; Qadri, Firdausi; Mannoor, Kaiissar

2018-01-02

Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and electrophortic indices in order to avoid false positive and false negative results.

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2011 CFR

2011-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Marina Del Rey, CA. 80.1118...

The Moon Phases in a Paper Box. (Spanish Title: Las Fases de la Luna en Una Caja de Cartón.) As Fases da Lua Numa Caixa de Papelão

NASA Astrophysics Data System (ADS)

de Fátima O. Saraiva, Maria; Amador, Cláudio B.; Kemper, Érico; Goulart, Paulo; Muller, Angela

2007-12-01

We present a very simple concrete model to demonstrate the concept of phases of an illuminated body. The main objective of our model is to help the understanding of the Moon phases as viewed from the perspective of an observer on Earth. The material allows the visualization of two important effects: (1st) even though all the time half Moon is illuminated by the Sun, we see different fractions of the illuminated Moon surface, depending on our angle of sight; (2nd) the orientation of the convex part of the Moon in the crescent and waning phases on the sky also depends on our perspective from Earth. The use of a closed box allows one to see the contrast among the different phases with no need of a dark room. We also present a text on the Moon phases, emphasizing the dependence of the aspect of the bright part on the angle of sight. En este trabajo proponemos la construcción de material didáctico de bajo costo para demostración del concepto de fases de un cuerpo iluminado. El principal objetivo de nuestro material es facilitar la comprensión de las fases de la Luna desde la perspectiva de un observador en la Tierra. El material ayuda la visualización de dos efectos importantes: (1º) a pesar de tener siempre la mitad de la Luna (representada por una bolita de espuma plástica o de ping-pong), iluminada por el Sol ( representado por una fuente de luz natural o artificial), vemos diferentes fracciones de su superficie iluminada, dependiendo del ángulo por el cual la vemos; (2º) la orientación del borde convexo de la Luna en las fases Creciente y Menguante también depende de la perspectiva por la cual la miramos desde la Tierra. El uso de una caja cerrada permite observar el contraste entre las diferentes fases sin necesidad de estar en un recinto oscuro. Presentamos también un texto explicativo sobre las fases de la Luna, enfatizando la dependencia de la apariencia de la parte iluminada con el ángulo de visión. Neste trabalho propomos a construção de material didático de baixo custo para demonstração do conceito de fases de um corpo iluminado. O principal objetivo de nosso material é facilitar a compreensão das fases da Lua da perspectiva de um observador na Terra. O material ajuda na visualização de dois efeitos importantes: (1º) mesmo tendo sempre a metade da "Lua" (representada por uma bolinha de isopor ou de ping-pong) iluminada pelo "Sol" (representado por uma fonte de luz natural ou artificial), nós vemos diferentes frações de sua superfície iluminada, dependendo do ângulo pelo qual a olhamos; (2º) a orientação da borda convexa da Lua nas fases Crescente e Minguante também depende da perspectiva pela qual a olhamos da Terra. O uso de uma caixa fechada permite observar o contraste entre as diferentes fases sem necessidade de estar em uma sala escurecida. Apresentamos também um texto explicativo sobre fases da Lua, enfatizando a dependência da aparência da parte iluminada com o ângulo de visada.

8th Argentinean Bioengineering Society Conference (SABI 2011) and 7th Clinical Engineering Meeting

NASA Astrophysics Data System (ADS)

Meschino, Gustavo Javier; Ballarin, Virginia L.

2011-12-01

In September 2011, the Eighteenth Edition of the Argentinean Bioengineering Society Conference (SABI 2011) and Seventh Clinical Engineering Meeting were held in Mar del Plata, Argetina. The Mar del Plata SABI Regional and the School of Engineering of the Universidad Nacional de Mar del Plata invited All bioengineers, engineers, physicists, mathematicians, biologists, physicians and health professionals working in the field of Bioengineering to participate in this event. The overall objectives of the Conference were: To provide discussion of scientific research results in Bioengineering and Clinical Engineering. To promote technological development experiences. To strengthen the institutional and scientific communication links in the area of Bioengineering, mainly between Universities of Latin America. To encourage students, teachers, researchers and professionals to establish exchanges of experiences and knowledge. To provide biomedical engineering technology solutions to the society and contributing ideas for low cost care. Conference photograph Conference photograph Conference photograph Conference photograph EXECUTIVE COMMITTEE SABI 2011 Chair Dra Virginia L Ballarin Universidad Nacional de Mar del Plata Co-Chair Dra Teresita R Cuadrado Universidad Nacional de Mar del Plata - CONICET Local Comittee Dr Gustavo Abraham Universidad Nacional de Mar del Plata - CONICET Dra Josefina Ballarre Universidad Nacional de Mar del Plata - CONICET Dr Eduardo Blotta Universidad Nacional de Mar del Plata Dra Agustina Bouchet Universidad Nacional de Mar del Plata Dr Marcel Brun Universidad Nacional de Mar del Plata Dra Silvia Ceré Universidad Nacional de Mar del Plata - CONICET Dra Mariela Azul Gonzalez Universidad Nacional de Mar del Plata - CONICET Dra Lucia Isabel Passoni Universidad Nacional de Mar del Plata Dr Juan Ignacio Pastore Universidad Nacional de Mar del Plata - CONICET Dra Adriana Scandurra Universidad Nacional de Mar del Plata SCIENTIFIC ADVISORY COMMITTEE President Dr Gustavo Meschino Universidad Nacional de Mar del Plata Comittee Dr Gustavo Abraham Universidad Nacional de Mar del Plata - CONICET Mg Rubén Acevedo Universidad Nacional de Entre Ríos Ing Pablo Agüero Universidad Nacional de Mar del Plata Ing Mariela Ambrustolo Universidad Nacional de Mar del Plata Dr Ricardo Armentano Universidad Favaloro Dra Virginia L Ballarin Universidad Nacional de Mar del Plata Dra Josefina Ballarre Universidad Nacional de Mar del Plata - CONICET Dr Eduardo Blotta Universidad Nacional de Mar del Plata Ing Marco Benalcázar Universidad Nacional de Mar del Plata Mg Freddy Geovanny Benalcázar Palacios Escuela Superior Politécnica de Chimborazo, Ecuador Dr Roberto Boeri Universidad Nacional de Mar del Plata - CONICET - INTEMA Dra Agustina Bouchet Universidad Nacional de Mar del Plata Dr Ariel Braidot Universidad Nacional de Entre Ríos Dr Marcel Brun Universidad Nacional de Mar del Plata Dra Silvia Ceré Universidad Nacional de Mar del Plata - CONICET Ing Fernando Clara Universidad Nacional de Mar del Plata Dr Raúl Correa Prado Universidad Nacional de San Juan Bioing Pablo Cortez Universidad Nacional de Mar del Plata Dra Teresita R Cuadrado Universidad Nacional de Mar del Plata - CONICET Ing Eduardo De Forteza Universidad Favaloro Dra Mariana Del Fresno Universidad Nacional del Centro de la Provincia de Buenos Aires Dr Martín Diaz Informática Médica Hospital Aleman de Buenos Aires - GIBBA Ing Julio César Doumecq Universidad Nacional de Mar del Plata Mg Ana María Echenique Universidad Nacional de San Juan Bioing Pedro Escobar Universidad Nacional del Centro, Olavarría, Pcia de Buenos Aires Dr Fernando Daniel Farfán Universidad Nacional de Tucumán Dr Carmelo Felice Universidad Nacional de Tucumán - CONICET Dr Elmer Fernández Universidad Católica de Córdoba - CONICET Ing José Flores Universidad Nacional de Entre Ríos Dr Arturo Gayoso Universidad Nacional de Mar del Plata Dra Bioing Agustina Garcés Universidad Nacional de San Juan ¬- CONICET Bioing Luciano Gentile Universidad Favaloro Mg María Eugenia Gómez Universidad Nacional de San Juan Dr Claudio González Universidad Nacional de Mar del Plata Mg Esteban González Universidad Nacional de Mar del Plata Dra Mariela A Gonzalez Universidad Nacional de Mar del Plata - CONICET Dr Juan Pablo Graffigna Universidad Nacional de San Juan Dra Myriam Herrera Universidad Nacional de Tucumán - CONICET Dr Roberto Hidalgo Universidad Nacional de Mar del Plata Dr Roberto Isoardi Fundación Escuela de Medicina Nuclear de Mendoza - CNEA Dra Susana Jerez Universidad Nacional de Tucumán Dr Eric Laciar Universidad Nacional de San Juan - CONICET Bioing Roberto Leonarduzzi Universidad Nacional de Entre Ríos Mg Norberto Lerendegui Instituto Tecnológico de Buenos Aires Dra Natalia López Universidad Nacional de San Juan - CONICET Dra Rossana Madrid Universidad Nacional de Tucuman - CONICET Ing Florencia Montini Ballarin Universidad Nacional de Mar del Plata - CONICET Dra Emilce Moler Universidad Nacional de Mar del Plata Dr Jorge Castiñieira Moreira Universidad Nacional de Mar del Plata Dr Silvia Murialdo Universidad Nacional de Mar del Plata - CIC Dr Juan Manuel Olivera Universidad Nacional de Tucumán Dra Lucia Isabel Passoni Universidad Nacional de Mar del Plata Dr Juan Ignacio Pastore Universidad Nacional de Mar del Plata - CONICET Dra María Elisa Pérez Universidad Nacional de San Juan Mg Franco M Pessana Universidad Favaloro Dr Julio Politti Universidad Nacional de Tucumán Dr Marcelo Risk Universidad Nacional de Buenos Aires - CONICET Ing Raúl Rivera Universidad Nacional de Mar del Plata Mg Luis Rocha Universidad Nacional de Tucumán - SIPROSA Dra Silvia Rodrigo Universidad Nacional de San Juan Dra Viviana Rotger Universidad Nacional de Tucumán Dr Leonardo Rufiner Universidad Nacional de Entre Rios - CONICET Dra Estela Ruiz Universidad Nacional de Tucumán Dr Martín Santiago Universidad Nacional del Centro de la Provincia de Buenos Aires Dra Adriana Scandurra Universidad Nacional de Mar del Plata Ing Graciela Secreto Universidad Favaloro Mg Pablo Solarz Universidad Nacional de Tucumán Mg Carolina Tabernig Universidad Nacional de Entre Ríos Ing Ricardo Taborda Universidad Nacional de Córdoba Dra María Eugenia Torres Universidad Nacional de Entre Ríos - CONICET Ing Juan Carlos Tulli Universidad Nacional de Mar del Plata Dr Gerardo Tusman Hospital Privado de Comunidad, Mar del Plata Dr Santiago Urquiza Universidad Nacional de Mar del Plata Mg Andrés Valdez Universidad Nacional de San Juan Dr Máximo Valentinuzzi INSIBIO - CONICET - Universidad Nacional de Tucumán

Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3.

PubMed

Acar, Sezer; BinEssa, Huda A; Demir, Korcan; Al-Rijjal, Roua A; Zou, Minjing; Çatli, Gönül; Anık, Ahmet; Al-Enezi, Anwar F; Özışık, Seçil; Al-Faham, Manar S A; Abacı, Ayhan; Dündar, Bumin; Kattan, Walaa E; Alsagob, Maysoon; Kavukçu, Salih; Tamimi, Hamdi E; Meyer, Brian F; Böber, Ece; Shi, Yufei

2018-01-01

Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887-22,395,767del (179880 bp deletion including exon 16-22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood.

Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3

PubMed Central

Demir, Korcan; Al-Rijjal, Roua A.; Zou, Minjing; Çatli, Gönül; Anık, Ahmet; Al-Enezi, Anwar F.; Özışık, Seçil; Al-Faham, Manar S. A.; Abacı, Ayhan; Dündar, Bumin; Kattan, Walaa E.; Alsagob, Maysoon; Kavukçu, Salih; Tamimi, Hamdi E.; Meyer, Brian F.; Böber, Ece

2018-01-01

Background Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. Methodology Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. Results Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887–22,395,767del (179880 bp deletion including exon 16–22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. Conclusions This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood. PMID:29505567

The Human 343delT HSPB5 Chaperone Associated with Early-onset Skeletal Myopathy Causes Defects in Protein Solubility*

PubMed Central

Mitzelfelt, Katie A.; Limphong, Pattraranee; Choi, Melinda J.; Kondrat, Frances D. L.; Lai, Shuping; Kolander, Kurt D.; Kwok, Wai-Meng; Dai, Qiang; Grzybowski, Michael N.; Zhang, Huali; Taylor, Graydon M.; Lui, Qiang; Thao, Mai T.; Hudson, Judith A.; Barresi, Rita; Bushby, Kate; Jungbluth, Heinz; Wraige, Elizabeth; Geurts, Aron M.; Benesch, Justin L. P.; Riedel, Michael; Christians, Elisabeth S.; Minella, Alex C.; Benjamin, Ivor J.

2016-01-01

Mutations of HSPB5 (also known as CRYAB or αB-crystallin), a bona fide heat shock protein and molecular chaperone encoded by the HSPB5 (crystallin, alpha B) gene, are linked to multisystem disorders featuring variable combinations of cataracts, cardiomyopathy, and skeletal myopathy. This study aimed to investigate the pathological mechanisms involved in an early-onset myofibrillar myopathy manifesting in a child harboring a homozygous recessive mutation in HSPB5, 343delT. To study HSPB5 343delT protein dynamics, we utilize model cell culture systems including induced pluripotent stem cells derived from the 343delT patient (343delT/343delT) along with isogenic, heterozygous, gene-corrected control cells (WT KI/343delT) and BHK21 cells, a cell line lacking endogenous HSPB5 expression. 343delT/343delT and WT KI/343delT-induced pluripotent stem cell-derived skeletal myotubes and cardiomyocytes did not express detectable levels of 343delT protein, contributable to the extreme insolubility of the mutant protein. Overexpression of HSPB5 343delT resulted in insoluble mutant protein aggregates and induction of a cellular stress response. Co-expression of 343delT with WT prevented visible aggregation of 343delT and improved its solubility. Additionally, in vitro refolding of 343delT in the presence of WT rescued its solubility. We demonstrate an interaction between WT and 343delT both in vitro and within cells. These data support a loss-of-function model for the myopathy observed in the patient because the insoluble mutant would be unavailable to perform normal functions of HSPB5, although additional gain-of-function effects of the mutant protein cannot be excluded. Additionally, our data highlight the solubilization of 343delT by WT, concordant with the recessive inheritance of the disease and absence of symptoms in carrier individuals. PMID:27226619

Papiloma invertido sinunasal con invasión intracraneal: Reporte de caso y revisión bibliográfica

PubMed Central

Di Pietrantonio, Andrés; Asmus, Humberto; Ingratta, Christian; Brennan, Walter; Schulz, Javier; Carballo, Leandro

2018-01-01

Resumen IntroducciÓn: El papiloma invertido es una neoplasia benigna de los senos paranasales localmente agresiva con alto potencial de recurrencia y de malignización. La extensión intracraneal es infrecuente y más aún, la penetración dural, asociándose a menudo a la recurrencia de la enfermedad o a su degeneración en carcinoma de células escamosas. Caso clínico: Presentamos el caso de una paciente de 32 años que consultó por lesión exofítica en fosa nasal derecha y exoftalmos, asociada a cefalea, anosmia y disgeusia. Se estudió con TC cerebro, macizo facial y RM de encéfalo que evidencian lesión en fosa nasal derecha con ocupación de senos aéreos, osteólisis de pared medial orbitaria y base de cráneo anterior e invasión intracraneal frontal derecha, con efecto de masa y compresión del parénquima encefálico adyacente. Intervención: Se realizó una nasofibroscopía en primer tiempo con diagnóstico anatomopatológico de papiloma invertido y posteriormente resección de la lesión mediante doble abordaje más reconstrucción de la fosa craneal anterior. Se obtuvo diagnóstico definitivo de papiloma invertido de tipo Schneideriano con áreas de transformación atípica in situ. La paciente evolucionó de forma favorable y sin complicaciones, con permeabilidad de vía aérea superior, sin signos de recidiva lesional luego de 4 años de seguimiento. Conclusión: La invasión intracraneal de esta patología es sumamente infrecuente. Cuando existe, es indicador de agresividad y potencial recidiva, por lo que la exéresis completa de la misma define el pronóstico de la enfermedad. PMID:29430328

PubMed

Domínguez, Vanihamín; Aguiñiga, Itzen; Moreno, Leticia; Torres, Beatriz; Santiago-Osorio, Edelmiro

2017-12-01

Introducción. El caseinato de sodio, una sal de la caseína utilizada como agente proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e incrementar la producción de citocinas esenciales en dicho evento.Objetivo. Evaluar si el caseinato de sodio es capaz de inducir un efecto biológico en células de origen linfoide y la producción de citocinas involucradas con este linaje.Materiales y métodos: Se utilizaron ratones hembra BALB/c de 8 a 12 semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48 horas, por vía intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v). La población de linfocitos B y la incorporación de bromodesoxiuridina (BrdU) se analizaron mediante citometría de flujo. La detección de la interleucina 7 se evaluó mediante la técnica de ELISA.Resultados. Tras la inyección por vía intraperitoneal, el número de linfocitos B 220+ provenientes del bazo de ratones tratados con caseinato de sodio aumentó comparados con los que solo recibieron el vehículo como tratamiento (89,01±1,03 Vs. 75,66±2,08), así como la incorporación de BrdU en células B220+ (38,59±4,48 Vs. 11,82±1,04). Se evidenció, asimismo, el incremento en la concentración de la interleucina 7 (IL-7) en el suero de los ratones tratados con caseinato de sodio, comparados con los que solo recibieron el vehículo (62,1±17,5 Vs. 26,9±4,4 pg/ml).Conclusión. El caseinato de sodio fue capaz de aumentar el número de linfocitos B en bazo de ratones, así como inducir la producción de IL-7, citocina clave para la linfopoyesis B.

Evolución de estrellas de Helio

NASA Astrophysics Data System (ADS)

Panei, J. A.; Benvenuto, O. G.; Althaus, L. G.

Podríamos identificar a las estrellas de helio con estrellas Wolf-Rayet (WR) que han perdido su envoltura rica en hidrógeno ya sea porque las mismas pertenecen a sistemas binarios o a través de fuertes vientos estelares. Las WR representan una etapa evolucionaria normal de las estrellas masivas, cuya pérdida de masa es >= 3 × 10-5Msolar/yr y la cual es sufrida por la estrella en un tiempo de escala mucho menor que el tiempo en que se produce la quema del He. Esto garantiza la ``homogeneidad'' de las estrellas de helio para nuestros modelos. Este tipo de estrellas serían posibles progenitores de SN tipo Ib y Ic. Aquí presentamos un estudio sobre la evolución de estrellas de helio a partir de la secuencia principal de helio, pasando por el flash de carbono, hasta agotarlo en la región central; como así también la dependencia con la variable masa y con la pérdida de la misma para distintos tipos de masas. Para tal fin hemos utilizado un código de evolución estelar completo que realiza todas las reacciones de Fowler en forma simultánea. También se han tenido en cuenta los procesos de mezcla convectiva, los principales mecanismos de emisión de neutrinos y los efectos de la pérdida de masa. Las opacidades utilizadas fueron las de Rogers & Iglesias (1992). Debido a la pérdida de masa en este tipo de estrellas, hemos encontrado que los perfiles convectivos, la composición química, las condiciones centrales de temperatura y presión, luminosidad y temperatura efectiva dependen en forma esencial de la velocidad de pérdida de masa adoptada, lo que tendría profundas implicaciones en la evolución posterior de estos objetos.

Mitigating the effect of development on bats in England with derogation licensing.

PubMed

Stone, Emma Louise; Jones, Gareth; Harris, Stephen

2013-12-01

The Convention on Biological Diversity has catalyzed worldwide awareness of threats to biological diversity and stimulated global conservation strategies. These have led to national and international legislation and have generated debate about the most effective conservation actions. Under the EU Habitats Directive, all member states are obliged to establish a system for strict protection of species listed in Annex IV(a), which includes all bats. In England, this obligation has resulted in legislation that allows for derogation from strict protection under license, provided activities are undertaken to mitigate any potential negative effects on bat numbers. We used an evidence-based approach to assess the cost-effectiveness of mitigation strategies and the English bat-derogation licensing process as a whole. We analyzed data from 389 bat derogation licenses issued in England from 2003 to 2005 relating to 1776 roosts and 15 species to determine the nature and extent of development and mitigation activities and their effects on bats. Overall the effects of licensed activities on roosts were negative. Despite the level of protection afforded to bats, the majority (68%) of roosts for which derogation licenses were issued were destroyed. There were species-specific differences in the probability of roosts being destroyed, and impacts on roosts did not reflect a species' conservation status. Information provided by licensees was inadequate and inconsistent. Most licensees (67%) failed to submit postdevelopment reports, and postdevelopment monitoring was conducted at only 19% of sites. Despite a minimum of £4.13 million spent on mitigation structures for bats from 2003 to 2005, it was unclear whether the licensing process meets EU obligations. On the basis of our results, we believe there is a need to overhaul the licensing process, to establish a comprehensive, standardized postdevelopment monitoring system, and to demonstrate that mitigation is commensurate with Britain's legal obligations. Mitigando el Efecto del Desarrollo sobre los Murciélagos en Inglaterra con Licencias de Derogación. © 2013 Society for Conservation Biology.

Lichenometry dating of rock collapse related to the great Lisbon Earthquake (1755) at the SE part of Spain

NASA Astrophysics Data System (ADS)

Perez-Lopez, Raul; Rodriguez-Pascua, Miguel Angel; Silva, Pablo G.; Bischoff, James L.; Owen, Lewis A.; Giner-Robles, Jorge L.; Díez-Herrero, Andres

2010-05-01

"De una montaña, se desprendió una parte" (A large part of a mountain has fallen down). This sentence was extracted from an ancient text written at the end of the 18th Century, in relation with the great Earthquake of Lisbon in 1755 (Martínez-Solares, 2001), and describing the rock collapse recorded near the small town of Agramón, 50 km southeastward of Albacete city (SE of Spain). Up to now, archaeologists have suggested this rock collapse to the archaeological site of "El Tolmo de Minateda", a small butte (420 m long) of calcarenitic sandstone bedrock with a flat top and scarped cliffs (20m high) bordering the butte. This ancient city was habited by several civilizations from Bronze Ages to modern times (i.e. Iberians, Roman, Visigoths, Muslims, Medieval ages, etc.). The landscape of this area is characterized by a flat terrain with isolated relict structural buttes consisting of Late Neogene marine sandstones created by differential erosion. The site exhibits three different stages of massive rock collapse. The oldest is located at the north of the site while the younger is located at the south part of the site and affecting Visigothic stone carved tombs. Archaeologists have postulated that the youngest of these was triggered by the Lisbon earthquake of 1755. We have carried out a lichenometric analysis over the free-faces of the rock blocks, with the aim of testing the postulate. For our purpose, we have calculated the calibrated growth curve for Aspicilia Radiosa (Hoff.), which yields a linear growth of 0.2425 mm per yr (R2 = 0.97, N=20). This growth rate was determined for the time interval from 800 BP yrs to the present by two different approaches: (1) rates obtained from cemetery measurements (200 yrs BP) and (2) rates determined from well-dated archaeological monuments (200-800 yrs BP). Our analysis revealed that the age of the rock-falling was in the year 1754 AD ±4. Thus, our results confirm that this collapse of ca. 5000 m3 of volume was triggered by the great Lisbon Earthquake of 1755, suggesting an ESI macroseismic intensity ranging between VII and VIII (Michetti et al., 2007) from a locality located 660 km eastward away from the city of Lisbon. This value is in contrast with the EMS intensity of V-VI estimated by Martínez-Solares (2001). Martínez-Solares, J. M. (2001): Los efectos en España del Terremoto de Lisboa (1 de noviembre de 1755). Ed. Dirección General del Instituto Geográfico Nacional. Madrid. 756 p. (In Spanish). Michetti, et al. (2007): Intensity Scale ESI 2007. Memoria Descriptiva Carta Geologica Italiana, 74: 41.

Intertextual Sexual Politics: Illness and Desire in Enrique Gomez Carrillo's "Del amor", "del dolor y del vicio" and Aurora Caceres's "La rosa muerta"

ERIC Educational Resources Information Center

LaGreca, Nancy

2012-01-01

This study explores the intertextuality between Aurora Caceres's "La rosa muerta" (1914) and the novel "Del amor, del dolor y del vicio" (1898) by her ex-husband, Enrique Gomez Carrillo. Caceres strategically mentions Gomez Carrillo's novel in "La rosa muerta" to invite a reading of her work in dialogue with his. Both narratives follow the sexual…

Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children.

PubMed

Yanovski, J A; Diament, A L; Sovik, K N; Nguyen, T T; Li, H; Sebring, N G; Warden, C H

2000-06-01

Little is known about genes that affect childhood body weight. The objective of this study was to examine the association between alleles of the mitochondrial uncoupling protein 2 (UCP2) gene and obesity because UCP2 may influence energy expenditure. We related UCP2 genotype to body composition and resting energy expenditure in 105 children aged 6-10 y. Overweight children and nonoverweight children of overweight parents were genotyped for a 45-base pair deletion/insertion (del/ins) in 3'-untranslated region of exon 8 and for an exon 4 C to T transition. Eighty-nine children were genotyped for the exon 8 allele: 50 children had del/del, 33 had del/ins, and 6 had ins/ins. Mean (+/-SD) body mass index (BMI; in kg/m(2)) was greater for children with del/ins (24.1 +/- 5.9) than for children with del/del (20.4 +/- 4.8; P < 0.001). BMI of ins/ins children (23.7 +/- 7.8) was not significantly different from that of del/ins children. A greater BMI in del/ins children was independent of race and sex. Body composition was also different according to UCP2 genotype. All body circumferences and skinfold thicknesses examined were significantly greater in del/ins than in del/del children. Body fat mass as determined by dual-energy X-ray absorptiometry was also greater in del/ins than in del/del children (P < 0.005). For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the 3 exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype. The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight.

Told through the wine: A liquid chromatography-mass spectrometry interplatform comparison reveals the influence of the global approach on the final annotated metabolites in non-targeted metabolomics.

PubMed

Díaz, Ramon; Gallart-Ayala, Hector; Sancho, Juan V; Nuñez, Oscar; Zamora, Tatiana; Martins, Claudia P B; Hernández, Félix; Hernández-Cassou, Santiago; Saurina, Javier; Checa, Antonio

2016-02-12

This work focuses on the influence of the selected LC-HRMS platform on the final annotated compounds in non-targeted metabolomics. Two platforms that differed in columns, mobile phases, gradients, chromatographs, mass spectrometers (Orbitrap [Platform#1] and Q-TOF [Platform#2]), data processing and marker selection protocols were compared. A total of 42 wines samples from three different protected denomination of origin (PDO) were analyzed. At the feature level, good (O)PLS-DA models were obtained for both platforms (Q(2)[Platform#1]=0.89, 0.83 and 0.72; Q(2)[Platform#2]=0.86, 0.86 and 0.77 for Penedes, Ribera del Duero and Rioja wines respectively) with 100% correctly classified samples in all cases. At the annotated metabolite level, platforms proposed 9 and 8 annotated metabolites respectively which were identified by matching standards or the MS/MS spectra of the compounds. At this stage, there was no coincidence among platforms regarding the suggested metabolites. When screened on the raw data, 6 and 5 of these compounds were detected on the other platform with a similar trend. Some of the detected metabolites showed complimentary information when integrated on biological pathways. Through the use of some examples at the annotated metabolite level, possible explanations of this initial divergence on the results are presented. This work shows the complications that may arise on the comparison of non-targeted metabolomics platforms even when metabolite focused approaches are used in the identification. Copyright © 2016 Elsevier B.V. All rights reserved.

Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway.

PubMed

Maekawa, Tomoki; Hosur, Kavita; Abe, Toshiharu; Kantarci, Alpdogan; Ziogas, Athanasios; Wang, Baomei; Van Dyke, Thomas E; Chavakis, Triantafyllos; Hajishengallis, George

2015-09-16

Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del-1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBPβ. Specifically, IL-17 causes GSK-3β-dependent phosphorylation of C/EBPβ, which is associated with diminished C/EBPβ binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3β level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin-D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del-1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis.

Pharmacological and electrophysiological characterization of nine, single nucleotide polymorphisms of the hERG-encoded potassium channel

PubMed Central

Männikkö, R; Overend, G; Perrey, C; Gavaghan, CL; Valentin, J-P; Morten, J; Armstrong, M; Pollard, CE

2010-01-01

Background and purpose: Potencies of compounds blocking KV11.1 [human ether-ago-go-related gene (hERG)] are commonly assessed using cell lines expressing the Caucasian wild-type (WT) variant. Here we tested whether such potencies would be different for hERG single nucleotide polymorphisms (SNPs). Experimental approach: SNPs (R176W, R181Q, Del187-189, P347S, K897T, A915V, P917L, R1047L, A1116V) and a binding-site mutant (Y652A) were expressed in Tet-On CHO-K1 cells. Potencies [mean IC50; lower/upper 95% confidence limit (CL)] of 48 hERG blockers was estimated by automated electrophysiology [IonWorks™ HT (IW)]. In phase one, rapid potency comparison of each WT-SNP combination was made for each compound. In phase two, any compound-SNP combinations from phase one where the WT upper/lower CL did not overlap with those of the SNPs were re-examined. Electrophysiological WT and SNP parameters were determined using conventional electrophysiology. Key results: IW detected the expected sixfold potency decrease for propafenone in Y652A. In phase one, the WT lower/upper CL did not overlap with those of the SNPs for 77 compound-SNP combinations. In phase two, 62/77 cases no longer yielded IC50 values with non-overlapping CLs. For seven of the remaining 15 cases, there were non-overlapping CLs but in the opposite direction. For the eight compound-SNP combinations with non-overlapping CLs in the same direction as for phase 1, potencies were never more than twofold apart. The only statistically significant electrophysiological difference was the voltage dependence of activation of R1047L. Conclusion and implications: Potencies of hERG channel blockers defined using the Caucasian WT sequence, in this in vitro assay, were representative of potencies for common SNPs. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 PMID:19673885

DEL phenotype.

PubMed

Kwon, Dong H; Sandler, S G; Flegel, Willy A

2017-09-01

DEL red blood cells (RBCs) type as D- by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent of African individuals who are D-, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D- recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are transfused as D- annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.

Calentamiento global : ¿Efecto invernadero o actividad solar?

NASA Astrophysics Data System (ADS)

Mauas, P. J. D.

Here we discuss some evidences suggesting that solar activity affects the terrestrial climate. We pay particular attention to claims, made by different authors, that global warming is due to an increase in solar activity and not to anthropogenic causes like, mainly, the greenhouse effect. We conclude that, although there are evidences suggesting that solar activity affects the climate at Earth, it seems doubtful that this is the main cause of global warming.

Distintas Modalidades de Aproximar la Educacion al Mundo Productivo: Efectos sobre Variables Psico-Sociales en los Alumnos (Distinct Modalities in Approaching Education for the Productive World: Effects of Socio-psychological Variables on Students).

ERIC Educational Resources Information Center

Hidalgo, Abelardo Castro; Carrasco, Decler Martinez; Alegria, Jorge Alegria; Elevancini, Cecilia Maldonado

2000-01-01

States that since the 1990s, professional technical education has produced profound transformations in the relationship between education and work in Chile. Examines in a study how modalities of bringing students to the world of work have affected students' socio-psychological characteristics in comparison to training received from traditional…

Relativistic Calculations and Measurements of Energies, Auger Rates, and Lifetimes.

DTIC Science & Technology

1982-12-01

Research and Industry, Denton, Texas, 8-10 November 1982. 7. B. Crasemann: "Efectos Relativ’sticos y de QED Sobre las Transiciones Rayos - X y Auger Entre...INNER-SHELL IONIZATION BY PROTONS X -RAY EMISSION BREIT INTERACTION AUGER TRANSITIONS DIRAC-HARTREE-SLATER COMPUTATIONS SYNCHROTRON RADIATION RESONANT...computations, including relativistic and quantum- electrodynamic effects, of atomic energy levels and of x -ray and Auger transitions in atoms with one or

ASSOCIATIONS BETWEEN UNCOUPLING PROTEIN 2, BODY COMPOSITION, AND RESTING ENERGY EXPENDITURE IN LEAN AND OBESE AFRICAN AMERICAN, CAUCASIAN, AND ASIAN CHILDREN

PubMed Central

Yanovski, J.A.; Diament, A.L.; Sovik, K.N.; Nguyen, T.T.; Li, H.; Sebring, N.G.; Warden, C.H.

2015-01-01

Background Little is known about genes affecting childhood body weight. Objective To examine alleles of the mitochondrial uncoupling protein-2 (UCP2) gene for association with obesity, since UCP2 may influence energy expenditure. Design We related UCP2 genotype to body composition, and to resting energy expenditure, in 105 children aged 6–10y. Overweight children and non-overweight children of overweight parents were genotyped for a 45 bp deletion/insertion (del/ins) in 3’ UTR of exon 8 and for an exon 4 C to T transition. Results 89 children were genotyped for the exon 8 allele: 50 children had del/del, 33 del/ins, and 6 ins/ins. Body mass index (BMI) was greater for del/ins (24.1 ± 5.9 kg/m2) than for del/del (20.4 ± 4.8 kg/m2, p<0.001). BMI of ins/ins (23.7 ± 7.8 kg/m2) was not different from del/ins. This effect was independent of race and gender (ANOVAs, p< 0.05). Body composition was also different according to UCP2 genotype. All body circumferences and skin fold thicknesses examined were significantly greater in del/ins than in del/del. DXA body fat mass (p<0.005) was also greater in del/ins than del/del. For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the three exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype. Conclusion The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight. PMID:10837279

Identification of two novel compound heterozygous mutations of ADGRV1 in a Chinese family with Usher syndrome type IIC.

PubMed

Zhang, Nian; Wang, Juan; Liu, Shuting; Liu, Mugen; Jiang, Fagang

2018-08-01

To describe the clinical and genetic findings in a Chinese family with three sibs diagnosed with Usher syndrome type IIC. Four members received ophthalmic and otologic tests to ascertain the clinical characteristics. According to the clinical phenotype, we focused attention on a total of 658 genes associated with them. We screened the possible pathogenic mutation sites, used Sanger to exclude the false positive and verified whether there were co-segregated among the family members. Typical fundus features found in the proband supported the diagnosis of retinitis pigmentosa (RP). Audiometric test indicated moderate to severe sensorineural hearing impairment while the vestibular function was normal. Whole-exome sequencing identified the presence of two novel compound heterozygous mutations in ADGRV1, a known gene responsible for Usher syndrome type IIC. Mutationc.15008delG/p.Gly5003AlafsTer13 was inherited from the mother while c.18383_18386dupACAG/p.His6130GlnfsTer84 was inherited from the father, and they were co-segregated with the disease phenotype in the family. The mutations found in our study not only broaden the mutation spectrum of ADGRV1, but also provide assistances for future genetic diagnosis and treatment for Usher syndrome patients.

Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings.

PubMed

Mozzillo, Enza; Melis, Daniela; Falco, Mariateresa; Fattorusso, Valentina; Taurisano, Roberta; Flanagan, Sarah E; Ellard, Sian; Franzese, Adriana

2013-08-01

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disease caused by loss of function mutations in the SLC19A2 gene. TRMA is characterized by anemia, deafness, and diabetes. In some cases, optic atrophy or more rarely retinitis pigmentosa is noted. We now report two sisters, the eldest of which presented to a different hospital during childhood with sensorineural deafness, which was treated with a hearing prosthesis, insulin requiring diabetes, retinitis pigmentosa, optic atrophy, and macrocytic anemia. These features initially suggested a clinical diagnosis of Wolfram syndrome (WS). Therapy with thiamine was initiated which resulted in the resolution of the anemia. The younger sister, who was affected with sensorineural deafness, was referred to our hospital for non-autoimmune diabetes. She was found to have macrocytosis and ocular abnormalities. Because a diagnosis of TRMA was suspected, therapy with insulin and thiamine was started. Sequencing analysis of the SLC19A2 gene identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in both sisters. Non-autoimmune diabetes associated with deafness and macrocytosis, without anemia, suggests a diagnosis of TRMA. Patients clinically diagnosed with WS with anemia and/or macrocytosis should be reevaluated for TRMA. © 2012 John Wiley & Sons A/S.

Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities.

PubMed

Nakajima, Junya; Oana, Shingo; Sakaguchi, Tomohiro; Nakashima, Mitsuko; Numabe, Hironao; Kawashima, Hisashi; Matsumoto, Naomichi; Miyake, Noriko

2018-04-01

The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.

Telephone interventions for adherence to colpocytological examination.

PubMed

Lima, Thais Marques; Nicolau, Ana Izabel Oliveira; Carvalho, Francisco Herlânio Costa; Vasconcelos, Camila Teixeira Moreira; Aquino, Priscila de Souza; Pinheiro, Ana Karina Bezerra

2017-02-06

to test the effects of behavioral and educational intervention by telephone on adherence of women with inappropriate periodicity to colpocytological examination. quasi-experimental study with a sample of 524 women, selected with the following inclusion criteria: be aged between 25 and 64 years, have initiated sexual activity, have inappropriate periodicity of examination and have mobile or landline phone. The women were divided into two groups for application of behavioral and educational intervention by telephone. It was used an intervention script according to the principles of Motivational Interviewing. on comparing the results before and after the behavioral and educational interventions, it was found that there was a statistically significant change (p = 0.0283) with increase of knowledge of women who participated in the educational intervention. There was no change in the attitude of women of any of the groups and there was an increase of adherence to colpocytological examination in both groups (p < 0.0001), with greater adherence of women participating in the behavioral group (66.8%). the behavioral and educational interventions by phone were effective in the adherence of women to colpocytological examination, representing important strategies for permanent health education and promotion of care for the prevention of cervical cancer. testar os efeitos de intervenção comportamental e educativa por telefone na adesão das mulheres com periodicidade inadequada ao exame colpocitológico. estudo quase-experimental, com amostra constituída por 524 mulheres selecionadas conforme os critérios de inclusão: estar na faixa etária entre 25 e 64 anos, ter iniciado atividade sexual, estar com a periodicidade do exame inadequada e possuir telefone móvel ou fixo. As mulheres foram divididas em dois grupos para aplicação da intervenção comportamental e educativa por telefone. Utilizou-se um roteiro de intervenção segundo os preceitos da Entrevista Motivacional. ao comparar antes e depois das intervenções comportamental e educativa constatou-se que houve uma mudança estatisticamente significativa (p = 0,0283) no aumento do conhecimento das mulheres que participaram da intervenção educativa; não houve mudança comprovada na atitude das mulheres de nenhum dos grupos e houve um aumento da adesão ao exame colpocitológico nos dois grupos (p < 0,0001), com maior adesão das mulheres que participaram do grupo comportamental (66,8%). as intervenções comportamentais e educativas por telefone foram eficazes na adesão das mulheres ao exame colpocitológico, representando estratégias importantes para educação permanente em saúde, promovendo a atenção para a prevenção do câncer cérvico-uterino. comprobar los efectos de intervención comportamental y educativa por teléfono en la adhesión de las mujeres, con periodicidad inadecuada, al examen de citología vaginal. estudio casi experimental, con muestra constituida por 524 mujeres seleccionadas conforme a los siguientes criterios de inclusión: estar en el intervalo etario entre 25 y 64 años, haber iniciado actividad sexual, estar con la periodicidad del examen inadecuada y poseer teléfono móvil o fijo. Las mujeres fueron divididas en dos grupos para aplicación de la intervención comportamental y educativa por teléfono. Se utilizó una guía de intervención según los preceptos de la Entrevista Motivacional. al comparar antes y después de la intervención comportamental y educativa se constató que hubo un cambio estadísticamente significativo (p = 0,0283) en el aumento del conocimiento de las mujeres que participaron de la intervención educativa; no hubo cambio comprobado en la actitud de las mujeres de ninguno de los grupos y hubo un aumento de la adhesión al examen de citología vaginal en los dos grupos (p < 0,0001), con mayor adhesión de las mujeres que participaron del grupo comportamental (66,8%). las intervenciones comportamentales y educativas por teléfono fueron eficaces en obtener la adhesión de las mujeres al examen de citología vaginal, representando estrategias importantes para una educación permanente en salud y promoviendo la atención para la prevención del cáncer del cuello uterino.

Modelo semi-empírico de protuberancia solar a partir del diagnóstico de densidades

NASA Astrophysics Data System (ADS)

Cirigliano, D.; Vial, J. C.; Rovira, M.

A partir de la observación del espectro del quintuplete de C III alrededor de 1175 Å, se ha realizado el diagnóstico de la densidad y presión electrónica, basado en el cálculo del cociente de las intensidades observadas. Una vez establecida la densidad electrónica, y con el cálculo de las velocidades Doppler, hemos investigado el flujo de masa en la protuberancia en función de la temperatura. Estableciendo como hipótesis la conservación del número de partículas que ingresan y salen del cuerpo de la protuberancia, se investiga la variación del área de un tubo de flujo semi-empírico en función de la temperatura. A partir de dicho diagnóstico, se examina el comportamiento del radio del tubo magnético en función de la temperatura, los que dan cuenta de la abertura de las líneas de campo magnético que confinan el plasma y de la divergencia del campo magnético en diferentes alturas de la atmósfera solar.

Del(20q) in patients with chronic lymphocytic leukemia: a therapy-related abnormality involving lymphoid or myeloid cells.

PubMed

Yin, C Cameron; Tang, Guilin; Lu, Gary; Feng, Xiaoli; Keating, Michael J; Medeiros, L Jeffrey; Abruzzo, Lynne V

2015-08-01

Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ hybridization (FISH) analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain variable region) genes, and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morphologic evidence of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia with del(20q) acquired after therapy is heterogeneous. In cases with morphologic evidence of dysplasia, the del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, the del(20q) may represent clonal evolution and disease progression. Combining morphologic analysis with FISH for del(20q) or performing FISH on immunomagnetically selected sub-populations to localize the cell population with this abnormality may help guide patient management.

Del(20q) in patients with chronic lymphocytic leukemia: A therapy-related abnormality involving lymphoid or myeloid cells

PubMed Central

Yin, C. Cameron; Tang, Guilin; Lu, Gary; Feng, Xiaoli; Keating, Michael J.; Medeiros, L. Jeffrey; Abruzzo, Lynne V.

2015-01-01

Del(20q), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. FISH analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 27/64 (42%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV genes and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morphologic evidence of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia with del(20q) acquired after therapy is heterogeneous. In cases with morphologic evidence of dysplasia, the del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, the del(20q) may represent clonal evolution and disease progression. Combining morphologic analysis with FISH for del(20q) or performing FISH on immunomagnetically-selected subpopulations to localize the cell population with this abnormality may help guide patient management. PMID:25953391

Increasing Naval Security Cooperation between the U.S., Chile and Peru

DTIC Science & Technology

2009-03-01

del Mar: La Marina de Guerra en la historia del Perú (Lima: Marina de Guerra del Perú, 1994), 184. 108 Ibid., 188. 109 Ibid., 191-193. 42 “the...La Marina de Guerra en la historia del Perú, 205. 111 Ibid. 112 Ibid., 210. 113 Ibid., 229. 114 Ibid., 230. 115 Ibid., 246. 43 contributed to...la Puente Brunke, Los Hombres del Mar: La Marina de Guerra en la historia del Perú, 252. 117 Ibid., 264. 118 Ibid., 302. 119 Ibid., 342. 44

Novel Founder Mutation in FANCA Gene (c.3446_3449dupCCCT) Among Romani Patients from the Balkan Region.

PubMed

Dimishkovska, Marija; Kotori, Vjosa Mulliqi; Gucev, Zoran; Kocheva, Svetlana; Polenakovic, Momir; Plaseska-Karanfilska, Dijana

2018-01-20

Fanconi anemia is a rare autosomal recessive or X-linked disorder characterised by clinical and genetic heterogeneity. Most fanconi anemia patients harbour homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~10%) or FANCD2 (3-6%) genes. We have already reported the FANCA variant c.190-256_283+1680del2040dupC as a founder mutation among Macedonian fanconi anemia patients of Gypsy-like ethnic origin. Here, we present a novel FANCA mutation in two patients from Macedonia and Kosovo. The novel FANCA mutation c.3446_3449dupCCCT was identified in two fanconi anemia patients with Romany ethnicity; a 2-year-old girl from Macedonia who is a compound heterozygote for a previously reported FANCA c.190-256_283+1680del2040dupC and the novel mutation and a 10-year-old girl from Kosovo who is a homozygote for the novel FANCA c.3446_3449dupCCCT mutation. The novel mutation is located in exon 35 in the FAAP20-binding domain which plays a crucial role in the FANCA -FAAP20 interaction and is required for integrity of the fanconi anemia pathway. The finding of the FANCA c.3446_3449dupCCCT mutation in two unrelated FA patients with Romani ethnicity from Macedonia and Kosovo suggests it is a founder mutation in the Romani population living in the Balkan region.

Fanconi-Bickel syndrome: GLUT2 mutations associated with a mild phenotype.

PubMed

Grünert, Sarah Catharina; Schwab, Karl Otfried; Pohl, Martin; Sass, Jörn Oliver; Santer, René

2012-03-01

Fanconi-Bickel syndrome (FBS, OMIM #227810), a congenital disorder of carbohydrate metabolism, is caused by mutations in GLUT2 (SLC2A2), the gene encoding the glucose transporter protein-2. The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal tubular nephropathy, rickets, and severe short stature. We report on two siblings with FBS and an unusually mild clinical course. A 9.5-year-old boy with failure to thrive was diagnosed at the age of 9 months, his younger sister (4.5 years) was investigated in the first months of life and also diagnosed with FBS. Both patients were found to be compound heterozygous for the novel GLUT2 (SLC2A2) mutations c.457_462delCTTATA (p.153_4delLI) and c.1250C>G (p.P417R). On a diet restricted in free glucose and galactose, both children showed normal growth. Hepatomegaly, nephromegaly and hypophosphatemic rickets have never been observed. Glucosuria and tubular proteinuria were only mild compared to previously reported patients with FBS. This report describes an unusually mild phenotype of FBS expanding the spectrum of this disease. Some clinical signs that have been considered hallmarks of FBS like hepatomegaly and short stature may be absent in this condition. As a consequence, clinicians will have to look for GLUT2 mutations even in patients with isolated glucosuria. Copyright © 2011 Elsevier Inc. All rights reserved.

[Rapid prenatal genetic diagnosis of a fetus with a high risk for Morquio A syndrome].

PubMed

Guo, Yi-bin; Ai, Yang; Zhao, Yan; Tang, Jia; Jiang, Wei-ying; Du, Min-lian; Ma, Hua-mei; Zhong, Yan-fang

2012-04-01

To provide rapid and accurate prenatal genetic diagnosis for a fetus with high risk of Morquio A syndrome. Based on ascertained etiology of the proband and genotypes of the parents, particular mutations of the GALNS gene were screened at 10th gestational week with amplification refractory mutation system (ARMS), denaturing high performance liquid chromatography (DHPLC), and direct DNA sequencing. DHPLC screening has identified abnormal double peaks in the PCR products of exons 1 and 10, whilst only a single peak was detected in normal controls. Amplification of ARMS specific primers derived a specific product for the fetus's gene, whilst no similar product was detected in normal controls. Sequencing of PCR products confirmed that exons 1 and 10 of the GALNS gene from the fetus contained a heterozygous paternal c.106-111 del (p.L36-L37 del) deletion and a heterozygous maternal c.1097 T>C (p.L366P) missense mutation, which resulted in a compound heterozygote status. The fetus was diagnosed with Morquio A syndrome and a genotype similar to the proband. Termination of the pregnancy was recommended. Combined ARMS, DHPLC and DNA sequencing are effective for rapid and accurate prenatal diagnosis for fetus with a high risk for Morquio A syndrome. Such methods are particularly suitable for early diagnosis when pathogenesis is clear. Furthermore, combined ARMS and DHPLC are suitable for rapid processing of large numbers of samples for the identification of new mutations.

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

PubMed

Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

2018-01-01

A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

Characteristics and outcome of myelodysplastic syndromes (MDS) with isolated 20q deletion: a report on 62 cases.

PubMed

Braun, Thorsten; de Botton, Stéphane; Taksin, Anne-Laure; Park, Sophie; Beyne-Rauzy, Odile; Coiteux, Valérie; Sapena, Rosa; Lazareth, Anne; Leroux, Geneviève; Guenda, Khaled; Cassinat, Bruno; Fontenay, Michaela; Vey, Norbert; Guerci, Agnès; Dreyfus, François; Bordessoule, Dominique; Stamatoullas, Aspasia; Castaigne, Sylvie; Terré, Christine; Eclache, Virginie; Fenaux, Pierre; Adès, Lionel

2011-07-01

Isolated 20q deletion is common in MDS and considered of good prognosis, but no large series have been reported. We compared characteristics of 62 MDS patients with isolated del 20q, 36 patients with del 20q and other cytogenetic abnormalities, and 1335 MDS patients without del20q. Significant differences between MDS with isolated del 20q and patients without del 20q were lower platelet count (mean 144 vs. 196 G/l, p=0.005), lower marrow blast count (mean 3.9% vs. 5.6%, p=0.0008), and higher reticulocyte count (mean 72.5 vs. 51.7 G/l, p=0.04). Ten (16%) patients with isolated del 20q had Hb>12 g/dl and platelets <100 G/l, compared to 7.3% of patients without del 20q (p=0.025). Review of marrow slides of those 10 patients showed that could be readily identified as MDS prior to cytogenetics. Fourteen percent of patients with isolated del 20q progressed to AML compared to 11% with one and 24% with several additional abnormalities. Median survival was 54 months in patients with isolated del 20q, not reached and 12 months for del 20q with one and several additional abnormalities, respectively (p=0.035) confirming the favorable prognosis of del 20q without complex abnormalities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Produccion Gaseosa del Cometa Halley: Erupciones Y Fotodisociacion del Radical OH

NASA Astrophysics Data System (ADS)

Silva, A. M.; Mirabel, I. F.

1990-11-01

RESUMEN:En este trabajo informamos la detecci6n de 20 erupciones en la li'nea de =18cm (1667MHz) del radical OH en el Cometa Halley.Las observaciones incluyen todos los monitoreos existentes y se extienden desde 120 dias antes del perihelio hasta 90 dias despues.Se detectan bruscos crecimientos en el flujo medido,hasta un factor 1O,seguidos por decaimientos lentos asociados con la fotodisociaci6n del OH. Se obtuvieron valores para el tiempo de vida fotoquimico del OH y del H2O basandose en el modelo desarrollado previamente por Silva(1988). Esos tiempos de vida estan de acuerdo con predicciones teoricas y con las observaciones en el Ultravioleta, y los resultados, los que son fuertemente dependientes de la velocidad heliocentrica del Coineta (variando hasta un factor 6), han sido calculados para varios rangos de velocidad entre +28 y -28 km/seg. Key wo'L :

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

Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng

Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild typemore » of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells. • Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.« less

Endogenous developmental endothelial locus-1 limits ischemia-related angiogenesis by blocking inflammation

PubMed Central

Klotzsche - von Ameln, Anne; Cremer, Sebastian; Hoffmann, Jedrzej; Schuster, Peggy; Khedr, Sherif; Korovina, Irina; Troulinaki, Maria; Neuwirth, Ales; Sprott, David; Chatzigeorgiou, Antonios; Economopoulou, Matina; Orlandi, Alessia; Hain, Andreas; Zeiher, Andreas M.; Deussen, Andreas; Hajishengallis, George; Dimmeler, Stefanie; Chavakis, Triantafyllos; Chavakis, Emmanouil

2017-01-01

We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin–dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischemia-related angiogenesis. Intriguingly, Del-1–deficient mice displayed increased neovascularization in two independent ischemic models (retinopathy of prematurity and hind-limb ischemia), as compared to Del-1–proficient mice. On the contrary, angiogenic sprouting in vitro or ex vivo (aortic ring assay) and physiological developmental retina angiogenesis were not affected by Del-1 deficiency. Mechanistically, the enhanced ischemic neovascularization in Del-1-deficiency was linked to higher infiltration of the ischemic tissue by CD45+ hematopoietic and immune cells. Moreover, Del-1-deficiency promoted β2-integrin–dependent adhesion of hematopoietic cells to endothelial cells in vitro, and the homing of hematopoietic progenitor cells and of immune cell populations to ischemic muscles in vivo. Consistently, the increased hind limb ischemia-related angiogenesis in Del-1 deficiency was completely reversed in mice lacking both Del-1 and the β2-integrin LFA-1. Additionally, enhanced retinopathy-associated neovascularization in Del-deficient mice was reversed by LFA-1 blockade. Our data reveal a hitherto unrecognized function of endogenous Del-1 as a local inhibitor of ischemia-induced angiogenesis by restraining LFA-1–dependent homing of pro-angiogenic hematopoietic cells to ischemic tissues. Our findings are relevant for the optimization of therapeutic approaches in the context of ischemic diseases. PMID:28447099

The Effect of Direct and Indirect Corrective Feedback on Students' Spelling Errors (El efecto de la retroalimentación directa e indirecta sobre los errores de ortografía de los estudiantes)

ERIC Educational Resources Information Center

Baleghizadeh, Sasan; Dadashi, Mehdi

2011-01-01

The study presented here is an attempt to examine the role of indirect feedback in promoting junior high school students' spelling accuracy in English. It compares the effect of direct feedback with indirect feedback on students' written work dictated by their teacher from their textbooks. Two classes were selected from the Zanjanrood District in…

The effects of work on the health of nurses who work in clinical surgery departments at university hospitals.

PubMed

Silva, Rosângela Marion da; Zeitoune, Regina Célia Gollner; Beck, Carmem Lúcia Colomé; Martino, Milva Maria Figueiredo de; Prestes, Francine Cassol

2016-08-08

to analyze the effects of work on the health of nurses who work in clinical surgery departments at university hospitals in relation to physical, social and psychological suffering and pain. a quantitative transversal study was carried out between 2012 and 2013 in four institutions in a state located in the south of Brazil. We studied 65 nurses who responded to questions on their habits. We also obtained sociodemographical information on them as well as conducting an evaluation on work relational damage using an evaluation scale. Associations were checked through the use of the Chi-Sqaure and Fisher's exact test. Correlations were checked using the Spearmann test. we found that physical ailments persisted and that there were connections between social and psychological pain/suffering and variable physical activities as well as connections with accidents in the work place and the option to work shifts. We noted correlations between social and psychological pain/suffering. nurses had their health compromised due to their work in clinical surgery departments. analisar os efeitos do trabalho na saúde de enfermeiros que atuam em clínicas cirúrgicas de hospitais universitários, relacionando-os aos danos físicos, sociais e psicológicos. estudo quantitativo, transversal, realizado entre 2012 e 2013 em quatro instituições de um Estado da região sul do Brasil. A amostra foi composta por 65 enfermeiros que responderam questões sobre os hábitos de vida e dados sociodemográficos e a Escala de Avaliação de Danos Relacionados ao Trabalho. Associações foram verificadas pelo teste Qui-Quadrado e Exato de Fisher e as correlações pelo teste de Spearmann. prevaleceu o adoecimento físico, encontrando associação entre os fatores Danos Sociais e Psicológicos e as variáveis prática de atividade física, acidente de trabalho e opção pelo turno de trabalho. Evidenciou-se correlação entre Danos Sociais e Psicológicos. o trabalho realizado por enfermeiros que atuam em clínica cirúrgica nas instituições hospitalares pesquisadas produz efeitos danosos à saúde. analizar los efectos del trabajo en la salud de enfermeros que actúan en clínicas quirúrgicas de hospitales universitarios, relacionándolos a daños físicos, sociales y psicológicos. estudio cuantitativo, transversal, realizado entre 2012 y 2013, en cuatro instituciones de un estado de la región sur de Brasil. La muestra estuvo compuesta por 65 enfermeros que respondieron preguntas sobre los hábitos de vida y datos sociodemográficos; se uso la Escala de Evaluación de Daños Relacionados al Trabajo. Las asociaciones fueron verificadas con el test Chi-Cuadrado y Exacto de Fisher y las correlaciones con el test de Spearmann. prevaleció la enfermedad física, encontrando asociación entre los factores Daños Sociales y Psicológicos y las variables: práctica de actividades físicas, accidente de trabajo y opción por el turno de trabajo. Se evidenció correlación entre Daños Sociales y Psicológicos. el trabajo realizado por enfermeros, que actúan en clínica quirúrgica en las instituciones hospitalarias investigadas, produce efectos que perjudican a la salud.

Acerca del moho

EPA Pesticide Factsheets

El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

Misura de Massa e Larghezza degli Stati $$x_1$$ e $$x_2$$ del Charmonio Formati in Interazioni $$p - \\bar{p}$$

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

Pallavicini, Marco

1995-01-01

Oggetto di questa tesi è la misura di alcune caratteristiche fisiche ( massa, larghezza, e larghezza parziale in p - p) degli stati 3 Pi e 3 A del charmonio, - overo del sistema legato di un quark "charm" e del suo antiquark-, nell'ambito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab (U.S.A).

Dissection of Insertion–Deletion Variants within Differentially Expressed Genes Involved in Wood Formation in Populus

PubMed Central

Gong, Chenrui; Du, Qingzhang; Xie, Jianbo; Quan, Mingyang; Chen, Beibei; Zhang, Deqiang

2018-01-01

Short insertions and deletions (InDels) are one of the major genetic variants and are distributed widely across the genome; however, few investigations of InDels have been conducted in long-lived perennial plants. Here, we employed a combination of RNA-seq and population resequencing to identify InDels within differentially expressed (DE) genes underlying wood formation in a natural population of Populus tomentosa (435 individuals) and utilized InDel-based association mapping to detect the causal variants under additive, dominance, and epistasis underlying growth and wood properties. In the present paper, 5,482 InDels detected from 629 DE genes showed uneven distributions throughout all 19 chromosomes, and 95.9% of these loci were diallelic InDels. Seventy-four InDels (positive false discovery rate q ≤ 0.10) from 68 genes exhibited significant additive/dominant effects on 10 growth and wood-properties, with an average of 14.7% phenotypic variance explained. Potential pleiotropy was observed in one-third of the InDels (representing 24 genes). Seven genes exhibited significantly differential expression among the genotypic classes of associated InDels, indicating possible important roles for these InDels. Epistasis analysis showed that overlapping interacting genes formed unique interconnected networks for each trait, supporting the putative biochemical links that control quantitative traits. Therefore, the identification and utilization of InDels in trees will be recognized as an effective marker system for molecular marker-assisted breeding applications, and further facilitate our understanding of quantitative genomics. PMID:29403506

Radio-Observaciones del OH EN la Coma del Cometa Halley Desde EL Hemisferio Sur

NASA Astrophysics Data System (ADS)

Silva, A. M.; Bajaja, E.; Morras, R.; Cersosimo, J. C.; Martin, M. C.; Arnal, E. M.; Poppel, W. G. L.; Colomb, F. R.; Mazzaro, J.; Olalde, J. C.; Boriakoff, V.; Mirabel, I. F.

1987-05-01

Se utilizó una antena de 30 metros del Instituto Argentino de Radioastronomía para observaciones diarias Cf ebrero a abril de 1986) de la transición en 1667 MHz ( λ = 18 cm) del OH en la coma del cometa Halley. De las observaciones realizadas se concluye: 1) El número promedio de moléculas de OH en la coma durante 37 días de observación fue de (8.9±3.5)x1034 moléculas, lo que implica una tasa de producción promedio de OH de 1.8x1029 moléculas seg-1 y consecuentemente una pérdida de masa promedio de 17±6 toneladas seg-1 . Este valor está de acuerdo con las mediciones realizadas por las sondas Vega y Giotto. 2) El monitoreo desde el lAR revela la existencia de variaciones bruscas en los flujos de absorción del OH. Estas variaciones son consistentes con los modelos que representan la producción gaseosa a partir de ejecciones y/o desprendimientos discretos de materia congelada del núcleo. 3) Las variaciones en la densidad de flujo son consistentes con las estimaciones de los tiem- pos de vida medios del H2O y del OH en presencia del campo de radiación solar. 4) Se encuentra una correlación entre la intensidad del flujo absorbido y anisotropías en Ia dinamica de la coma.

An evaluation of Delaware's DelTrac program : building an integrated transportation management system

DOT National Transportation Integrated Search

2004-06-01

The DelTrac deployment experience included both successes and unmet challenges. Programmatically, the DelTrac approach to managing ITS has been successful at creating a great deal of integration and cooperation between organizations at DelDOT. Stakeh...

An Annotated Bibliography of Latin American Military Journals.

DTIC Science & Technology

1965-12-01

CABALLERIA Y UNIDADES BLINDADAS) REVISTA DE INFANTERIA REVISTA DE INGENIERIA MILITÄR (Organo de la Academia Politecnica Militär) REVISTA DEL...Appendix--continued ■84- PERU BOLETIN DEL MINISTERIO DE GUERRA Y MARINA (Continued as MEMORIAL DEL EJERCITO) INFANTERIA INGENIERIA REVISTA DEL

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

PubMed Central

Stanton, Bruce A.; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials. PMID:26018799

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

PubMed

Stanton, Bruce A; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

In utero exposure to dioxins and dioxin-like compounds and anogenital distance in newborns and infants.

PubMed

Vafeiadi, Marina; Agramunt, Silvia; Papadopoulou, Eleni; Besselink, Harrie; Mathianaki, Kleopatra; Karakosta, Polyxeni; Spanaki, Ariana; Koutis, Antonis; Chatzi, Leda; Vrijheid, Martine; Kogevinas, Manolis

2013-01-01

Anogenital distance in animals is used as a measure of fetal androgen action. Prenatal exposure to dioxins and dioxin-like compounds in rodents causes reproductive changes in male offspring and decreases anogenital distance. We assessed whether in utero exposure to dioxins and dioxin-like compounds adversely influences anogenital distance in newborns and young children (median age, 16 months; range, 1-31 months). We measured anogenital distance among participants of the "Rhea" mother-child cohort study in Crete and the Hospital del Mar (HMAR) cohort in Barcelona. Anogenital distance (AGD; anus to upper penis), anoscrotal distance (ASD; anus to scrotum), and penis width (PW) were measured in 119 newborn and 239 young boys; anoclitoral (ACD; anus to clitoris) and anofourchetal distance (AFD; anus to fourchette) were measured in 118 newborn and 223 young girls. We estimated plasma dioxin-like activity in maternal blood samples collected at delivery with the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX®) bioassay. Anogenital distances were sexually dimorphic, being longer in males than females. Plasma dioxin-like activity was negatively associated with AGD in male newborns. The estimated change in AGD per 10 pg CALUX®-toxic equivalent/g lipid increase was -0.44 mm (95% CI: -0.80, -0.08) after adjusting for confounders. Negative but smaller and nonsignificant associations were observed for AGD in young boys. No associations were found in girls. Male infants may be susceptible to endocrine-disrupting effects of dioxins. Our findings are consistent with the experimental animal evidence used by the Food and Agriculture Organization/World Health Organization to set recommendations for human dioxin intake.

In Utero Exposure to Dioxins and Dioxin-like Compounds and Anogenital Distance in Newborns and Infants

PubMed Central

Vafeiadi, Marina; Agramunt, Silvia; Papadopoulou, Eleni; Besselink, Harrie; Mathianaki, Kleopatra; Karakosta, Polyxeni; Spanaki, Ariana; Koutis, Antonis; Chatzi, Leda; Vrijheid, Martine

2012-01-01

Background: Anogenital distance in animals is used as a measure of fetal androgen action. Prenatal exposure to dioxins and dioxin-like compounds in rodents causes reproductive changes in male offspring and decreases anogenital distance. Objective: We assessed whether in utero exposure to dioxins and dioxin-like compounds adversely influences anogenital distance in newborns and young children (median age, 16 months; range, 1–31 months). Methods: We measured anogenital distance among participants of the “Rhea” mother–child cohort study in Crete and the Hospital del Mar (HMAR) cohort in Barcelona. Anogenital distance (AGD; anus to upper penis), anoscrotal distance (ASD; anus to scrotum), and penis width (PW) were measured in 119 newborn and 239 young boys; anoclitoral (ACD; anus to clitoris) and anofourchetal distance (AFD; anus to fourchette) were measured in 118 newborn and 223 young girls. We estimated plasma dioxin-like activity in maternal blood samples collected at delivery with the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX®) bioassay. Results: Anogenital distances were sexually dimorphic, being longer in males than females. Plasma dioxin-like activity was negatively associated with AGD in male newborns. The estimated change in AGD per 10 pg CALUX®–toxic equivalent/g lipid increase was –0.44 mm (95% CI: –0.80, –0.08) after adjusting for confounders. Negative but smaller and nonsignificant associations were observed for AGD in young boys. No associations were found in girls. Conclusions: Male infants may be susceptible to endocrine-disrupting effects of dioxins. Our findings are consistent with the experimental animal evidence used by the Food and Agriculture Organization/World Health Organization to set recommendations for human dioxin intake. PMID:23171674

Wolfram Syndrome: New Mutations, Different Phenotype

PubMed Central

Pasquali, Lorenzo; Lugani, Francesca; Perri, Katia; Russo, Chiara; Tallone, Ramona; Ghiggeri, Gian Marco; Lorini, Renata; d'Annunzio, Giuseppe

2012-01-01

Background Wolfram Syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness identified by the acronym “DIDMOAD”. The WS gene, WFS1, encodes a transmembrane protein called Wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. WS is a rare disease, with an estimated prevalence of 1/550.000 children, with a carrier frequency of 1/354. The aim of our study was to determine the genotype of WS patients in order to establish a genotype/phenotype correlation. Methodology/Principal Findings We clinically evaluated 9 young patients from 9 unrelated families (6 males, 3 females). Basic criteria for WS clinical diagnosis were coexistence of insulin-treated diabetes mellitus and optic atrophy occurring before 15 years of age. Genetic analysis for WFS1 was performed by direct sequencing. Molecular sequencing revealed 5 heterozygous compound and 3 homozygous mutations. All of them were located in exon 8, except one in exon 4. In one proband only an heterozygous mutation (A684V) was found. Two new variants c.2663 C>A and c.1381 A>C were detected. Conclusions/Significance Our study increases the spectrum of WFS1 mutations with two novel variants. The male patient carrying the compound mutation [c.1060_1062delTTC]+[c.2663 C>A] showed the most severe phenotype: diabetes mellitus, optic atrophy (visual acuity 5/10), deafness with deep auditory bilaterally 8000 Hz, diabetes insipidus associated to reduced volume of posterior pituitary and pons. He died in bed at the age of 13 years. The other patient carrying the compound mutation [c.409_424dup16]+[c.1381 A>C] showed a less severe phenotype (DM, OA). PMID:22238590

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

NASA Astrophysics Data System (ADS)

Davila Montanez, Melissa

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

The residual and direct effects of reduced-risk and conventional miticides on twospotted spider mites, Tetranychus urticae (Acari: Tetranychidae) and predatory mites (Acari: Phytoseiidae)

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

Liburd, O.E.; White, J.C.; Rhodes, E.M.

2007-03-15

The residual effects of several reduced-risk and conventional miticides were evaluated in strawberries (Fragaria z ananassa Duchesne) on the twospotted spider mite (TSSM), Tetranychus urticae Koch (Acari: Tetranychidae) and on 2 predatory mites, Neoseiulus californicus McGregor and Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae). Experiments were conducted in the laboratory and greenhouse. The greenhouse experiments also tested the direct effects of the miticides on TSSM. The efficacy of conventional and reduced-risk miticides was evaluated on strawberry leaf discs and on whole plants for control of TSSM. Furthermore, the residual effects of these miticides were evaluated on whole strawberry plants against selective predatorymore » mites. For TSSM, 5 treatments were evaluated: a conventional miticide; fenbutatin-oxide (Vendex[reg]) and 3 reduced-risk miticides; binfenazate (Acramite 50WP[reg]), activated garlic extract (Repel[reg]), sesame seed and castor oil (Wipeout[reg]), and a water-treated control. For predatory mites, the residual effects of only Acramite[reg] and Vendex[reg] were evaluated. Acramite[reg] was the most effective acaricide in reducing TSSM populations in both the laboratory and greenhouse experiments. Vendex[reg] and Wipeout[reg] were also effective in the laboratory, but did not cause significant reduction of TSSM in the greenhouse. Repel[reg] was the least effective of the 4 pesticides evaluated. Neither Acramite[reg] nor Vendex[reg] had a significant effect on either predatory mite species. However, there appeared to be more predatory mites on the Vendex[reg]-treated plants than on the Acramite[reg]-treated plants. There were significantly more predatory mites of both species on the cue plants, which were inoculated with TSSM versus the non-cue plants, which were not inoculated. (author) [Spanish] Los efectos residuales en poblaciones de la 'arana roja', Tetranychus urticae Koch (Acari: Tetranichidae) y de los acaros predadores Neoseiulus californicus McGregor y Phytoseilus persimilis Athias-Henriot (Acari: Phytoseiidae) causados por varios acaricidas convencionales y de riesgo-reducido fueron evaluados en fresas (Fragaria x ananassa Duchense). Los experimentos fueron realizados en laboratorio e invernadero. Los experimentos en el invernadero evaluaron tambien el efecto directo de los acaricidas en la 'arana roja'. La eficacia para controlar la 'arana roja' de los acaricidas convencionales y de riesgo-reducido fue evaluada en discos de las hojas y en plantas de fresa, y los efectos residuales de los acaricidas en los acaros predadores fueron evaluados en plantas completas. Para la 'arana roja' se evaluaron cinco tratamientos: el acaricida convencional fenbutatin-oxido (Vendex[reg]), 3 acaricidas de riesgo-reducido binfenazate (Acaramite 50WP[reg]), extracto de ajo activado (Repel[reg]), aceite de semillas de ajonjoli y ricino (Wipeout[reg]) y un control tratado con agua. Para los acaros predadores solamente los efectos de Acaramite[reg] y Vendex[reg] fueron evaluados. Acaramite[reg] fue el tratamiento mas efectivo para la 'arana roja' en el laboratorio y el invernadero. Vendex[reg] y Wipeout[reg] fueron tambien efectivos en el laboratorio, pero no causaron una reduccion significativa de 'aranas rojas' en el invernadero. Repel[reg] fue el tratamiento evaluado menos eficaz. Ni Acaramite[reg] ni Vendex[reg] redujeron significativamente las poblaciones de acaros predadores. Sin embargo, aparentemente hay mas acaros predadores en Vendex[reg] que en Acaramite[reg]. Tambien se encontraron significativamente mas acaros predadores en plantas inoculadas que en plantas no inoculadas. (author)« less

An experiment of formation of charmoni states in annihilation P-Pbarra. Un esperimento di formazione di stati del charmonio in annichilazione P-Pbarra (in Italian)

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

Pallavicini, Marco

1995-01-01

Oggetto di questa tesi e la misura di alcune caratteristiche fisiche (massa, larghezza, e larghezza parziale in p -more » $$\\bar{p}$$) degli stati 3P 1 e 3P 2 del charmonio, -ovvero del sistema legato di un quark "charm" e del suo antiquark-, nell'amito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab.« less

Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials.

PubMed

Saccone, G; Khalifeh, A; Elimian, A; Bahrami, E; Chaman-Ara, K; Bahrami, M A; Berghella, V

2017-03-01

Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed. Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53-0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40-0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0.53 (95% CI, 0.31-0.91); very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared with 17-OHPC (18.7% vs 23.5%; RR, 0.63 (95% CI, 0.47-0.83); low quality of evidence). For the comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was not reached) and by at least one degree due to indirectness (different interventions). Daily vaginal progesterone (either suppository or gel) started at about 16 weeks' gestation is a reasonable, if not better, alternative to weekly 17-OHPC injection for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low or very low as assessed by GRADE, indicating that the true effect may be, or is likely to be, substantially different from the estimate of the effect. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. COMPARACIÓN ENTRE LA PROGESTERONA VAGINAL Y EL 17Α-HIDROXIPROGESTERONA CAPROATO INTRAMUSCULAR PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO ESPONTÁNEO RECURRENTE EN EMBARAZOS CON FETO ÚNICO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIOS: RESUMEN OBJETIVO: Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en inglés) por vía intramuscular con la progesterona por vía vaginal para la reducción del riesgo de parto pretérmino espontáneo (PPTE) en embarazos con feto único de gestantes con historial de PPTE. El objetivo de esta revisión sistemática y metaanálisis fue evaluar la eficacia de la progesterona vaginal en comparación con la 17-OHPC en la prevención de embarazos con feto único de gestantes con historial de PPTE. MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas para identificar todos los ECA con embarazos de feto único asintomáticos con historial de PPTE antes de ser asignados al azar a un tratamiento profiláctico, ya fuera con progesterona vaginal (grupo de intervención) o con 17-OHPC intramuscular (grupo de control). No se aplicaron restricciones respecto al idioma o la ubicación geográfica. El resultado primario fue PPTE < 34 semanas. Los resultados secundarios fueron PPTE <37 semanas, < 32 semanas, < 28 semanas y < 24 semanas, la reacción materna adversa al fármaco y los resultados neonatales. Las medidas del resumen se reportaron como riesgo relativo (RR) con IC del 95%. Para cada estudio incluido se evaluó el riesgo de sesgo. Se incluyeron tres ECA (680 mujeres). La media de la edad gestacional en el momento de la aleatorización fue de 16 semanas. A las mujeres se les administró progesterona hasta la semana 36 o hasta el parto. Con respecto a la progesterona vaginal, un estudio utilizó gel de 90 mg diariamente, otro utilizó un supositorio diario de 100 mg y el otro utilizó un supositorio diario de 200 mg. Todos los ECA incluidos en el grupo de comparación utilizaron 250 mg semanales de 17-OHPC por vía intramuscular. Las mujeres que recibieron progesterona vaginal tuvieron tasas significativamente más bajas de PPTE < 34 semanas (17,5% vs. 25,0%; RR 0,71 (IC 95%, 0,53-0,95); calidad de la evidencia baja) y < 32 semanas (8,9% vs. 14,5%; RR 0,62 (IC 95%, 0,40-0,94); calidad de evidencia baja), en comparación con las mujeres que recibieron 17-OHPC. No hubo diferencias significativas en las tasas de PPTE < 37 semanas, < 28 semanas y < 24 semanas. La tasa de mujeres que reportaron reacciones adversas a los medicamentos fue significativamente menor en el grupo de progesterona vaginal en comparación con el grupo de 17-OHPC (7,1% vs. 13,2%; RR 0,53 (IC 95%, 0,31-0,91); calidad de la evidencia muy baja). En cuanto a los resultados neonatales, la progesterona vaginal se asoció a una menor tasa de admisiones en la unidad neonatal de cuidados intensivos en comparación con la 17-OHPC (18,7% vs. 23,5%; RR 0,63 (IC 95%, 0,47-0,83); calidad de evidencia baja). Para la comparación del 17-OHPC con la progesterona vaginal se rebajó la calidad de las pruebas para todos los resultados en al menos un grado debido a imprecisiones (no se alcanzó el tamaño óptimo de la información) y en al menos un grado debido al carácter indirecto de los estudios (diferentes intervenciones). La progesterona vaginal administrada diariamente (ya fuera como supositorio o como gel) desde la semana 16 de gestación es una alternativa razonable, si no mejor, a una inyección semanal de 17-OHPC para la prevención de PPTE en mujeres con embarazos de feto único e historial de PPTE. Sin embargo, el nivel de calidad de las estimaciones del resumen fue bajo o muy bajo según lo evaluado por GRADE, lo que indica que el verdadero efecto puede ser, o es probable que sea, sustancialmente diferente de la estimación del efecto. 17Α-:META: : (randomized controlled trials,RCTs)(spontaneous preterm birth,SPTB)17α-(intramuscular 17α-hydroxyprogesterone caproate,17-OHPC)SPTB。metaSPTB17-OHPCSPTB。 : ,SPTBRCTs,RCTs()17-OHPC()。。34SPTB。37、32、2824SPTB,。(relative risk,RR)95%CI。。 : 3RCTs(680)。16。,36。,90 mg,100 mg,200 mg。,RCTs250 mg 17-OHPC。17-OHPC,34 [17.5%25.0%;RR,0.71(95% CI,0.53 ~ 0.95);]32[8.9%14.5%;RR,0.62(95% CI,0.40 ~ 0.94);]SPTB。37、2824SPTB。17-OHPC,[7.1%13.2%;RR,0.53(95% CI,0.31 ~ 0.91);]。,17-OHPC,[18.7%23.5%;RR,0.63(95% CI,0.47 ~ 0.83);]。17-OHPC,(),()。 : SPTBSPTB,16()17-OHPC,。,GRADE,,。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Confirmation of RAX gene involvement in human anophthalmia

PubMed Central

Lequeux, L.; Rio, Marlène; Vigouroux, Armelle; Titeux, Matthias; Etchevers, Heather; Malecaze, François; Chassaing, Nicolas; Calvas, Patrick

2008-01-01

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia and left microphthalmia and sclerocornea. Here, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909 C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia. PMID:18783408

Confirmation of RAX gene involvement in human anophthalmia.

PubMed

Lequeux, L; Rio, M; Vigouroux, A; Titeux, M; Etchevers, H; Malecaze, F; Chassaing, N; Calvas, P

2008-10-01

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia, left microphthalmia and sclerocornea. In this study, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia.

Regulation and Function of TIFAB in Myelodysplastic Syndrome

DTIC Science & Technology

2013-06-01

genomic alteration in MDS is deletion of chromosome 5q (del(5q)). MDS patients with an isolated del(5q) presenting with anemia, neutropenia , and...is deletion of chromosome 5q (del(5q)). MDS patients with an isolated del(5q) presenting with anemia, neutropenia , and elevated platelets associated

On the Determination of Perturbations in Planetary Motions

NASA Astrophysics Data System (ADS)

Brunini, A.

1990-11-01

ABSTRACT. The main goal of this paper is to give an alternative way when the physical reaiity is too difficult to interpret, in such form that small effects can be ignored in the force model of dynamical systems. RESUMEN. El principal objetivo de este trabajo es ofrecer una via alterna para cuando la realidad fisica es demasiado dificil de interpretar, en tal forma que los efectos pequefios puedan despreciarse en los modelos de fuerza de sistemas dinamicos. Key words: PLANETS AND SATELLITES-DYNAMICS

Efectos dinámicos de las resonancias orbitales en el Sistema Solar

NASA Astrophysics Data System (ADS)

Gallardo, T.

2016-08-01

We describe the different orbital resonances in the Solar System that primarily affect minor bodies and some satellites. We present an idea of how to study the two body and three body mean motion resonances, secular resonances and Kozai-Lidov mechanism and the conclusions that can be drawn from these studies. Weak resonances generate subtle periodic orbital variations and produce temporary concentrations of objects while strong resonances can generate large variations in eccentricity and inclination risking the orbital stability.

Effects of Classroom Assessment Practices in a Foreign Language Reading Course (Efectos de las Prácticas de Evaluación en el Salón de Clase de un Curso de Lectura en Lengua Extranjera (LE))

ERIC Educational Resources Information Center

Medina, Sergio Alonso Lopera

2015-01-01

This article analyzes the various types of information that alternative assessment and traditional assessment practices provided in an English foreign language (FL) reading course for graduate students at a public university in Medellín, Colombia. This study followed the principles of qualitative research, and a case study was used as a research…

Effects of Strategy Instruction in an EFL Reading Comprehension Course: A Case Study (Efectos de la instrucción de estrategias en un curso de comprensión de lectura en inglés como lengua extranjera: un estudio de caso)

ERIC Educational Resources Information Center

Lopera Medina, Sergio

2012-01-01

Strategy instruction is useful in teaching contexts. This paper examines the effects of strategy instruction in an EFL reading comprehension course carried out with 26 undergraduate students at a Colombian university. As a research method, a case study was implemented. There were three instruments with which to collect data: reading comprehension…

Kurt Gödels Brünner Verwandte

NASA Astrophysics Data System (ADS)

Müller, Dora

2007-11-01

The author of this memoir Dora Müller (born 1920) belongs - as well as Kurt Gödel-to the German minority playing an important role in the past life of Brno. The marriage of his son included her among the Gödels collaterals. She was chemist, but also pianist, historician, participant of antinacist movement and iniciator of Czech-German understanding after war. Following her personal experiences, remembrances of Gödels relatives and documental materials, she evokes the atmosphere of broader family milieu of Kurt Gödel.

Resolving the Orientation of Cylinders and Cuboids from Projected Area Measurements

DTIC Science & Technology

2016-05-01

fabs ( e1 ) + Ay * fabs ( e2...Az * fabs ( e3 ) - A_xy; 90 g = Ax * fabs ( e4 ) + Ay * fabs ( e5 ) + Az * fabs ( e6 ) - A_xz; 91 h = Ax * fabs ( e7 ) + Ay * fabs ( e8 ) + Az * fabs ( e9...b23 * h; 128 del_r = b31 * f + b32 * g + b33 * h; 129 130 p -= del_p; 131 y -= del_y; 132 r -= del_r; 133 134 if ( fabs ( del_p ) < TOL && fabs (

Assessment of Management to Mitigate Anthropogenic Effects on Large Whales

PubMed Central

Van Der Hoop, Julie M; Moore, Michael J; Barco, Susan G; Cole, Timothy VN; Daoust, Pierre-Yves; Henry, Allison G; McAlpine, Donald F; McLellan, William A; Wimmer, Tonya; Solow, Andrew R

2013-01-01

Abstract United States and Canadian governments have responded to legal requirements to reduce human-induced whale mortality via vessel strikes and entanglement in fishing gear by implementing a suite of regulatory actions. We analyzed the spatial and temporal patterns of mortality of large whales in the Northwest Atlantic (23.5°N to 48.0°N), 1970 through 2009, in the context of management changes. We used a multinomial logistic model fitted by maximum likelihood to detect trends in cause-specific mortalities with time. We compared the number of human-caused mortalities with U.S. federally established levels of potential biological removal (i.e., species-specific sustainable human-caused mortality). From 1970 through 2009, 1762 mortalities (all known) and serious injuries (likely fatal) involved 8 species of large whales. We determined cause of death for 43% of all mortalities; of those, 67% (502) resulted from human interactions. Entanglement in fishing gear was the primary cause of death across all species (n = 323), followed by natural causes (n = 248) and vessel strikes (n = 171). Established sustainable levels of mortality were consistently exceeded in 2 species by up to 650%. Probabilities of entanglement and vessel-strike mortality increased significantly from 1990 through 2009. There was no significant change in the local intensity of all or vessel-strike mortalities before and after 2003, the year after which numerous mitigation efforts were enacted. So far, regulatory efforts have not reduced the lethal effects of human activities to large whales on a population-range basis, although we do not exclude the possibility of success of targeted measures for specific local habitats that were not within the resolution of our analyses. It is unclear how shortfalls in management design or compliance relate to our findings. Analyses such as the one we conducted are crucial in critically evaluating wildlife-management decisions. The results of these analyses can provide managers with direction for modifying regulated measures and can be applied globally to mortality-driven conservation issues. Evaluación del Manejo para Mitigar Efectos Antropogénicos sobre Ballenas Mayores Resumen Los gobiernos de Estados Unidos y Canadá han respondido a requerimientos legales para reducir la mortalidad de ballenas inducida por humanos por medio de impacto con embarcaciones y enmarañamiento en artes de pesca mediante la implementación de un conjunto de acciones reguladoras. Analizamos los patrones espaciales y temporales de la mortalidad de ballenas mayores en el Atlántico Noroccidental (23.5°N a 48.0°N), de 1970 a 2009, en el contexto de cambios de manejo. Utilizamos un modelo logístico multinomial ajustado por la máxima probabilidad de detección de tendencias en mortalidades por causa específica en el tiempo. Comparamos el número de muertes provocadas por humanos con los niveles de remoción biológica potencial (i.e., mortalidad específica provocada por humanos sustentable). De 1970 a 2009, hubo 1762 muertes (conocidas) y lesiones serias (casi fatales) involucrando 8 especies de ballenas mayores. Determinamos la causa de 43% de todas las muertes; de ellas, 67% (502) resultaron de interacciones humanas. El enmarañamiento en artes de pesca fue la causa principal de muerte en todas las especies (n = 323), seguida de causas naturales (n = 248) e impacto de embarcaciones (n = 171). Los niveles sustentables de mortalidad establecidos fueron excedidos consistentemente hasta en 650% en 2 especies. Las probabilidades de muerte por enmarañamiento y por impacto de embarcaciones incrementaron significativamente de 1990 a 2009. No hubo cambio significativo en la intensidad local de mortalidad por todas las causas o por impacto de embarcaciones antes y después de 2003, año en el que se implementaron numerosos esfuerzos de mitigación. Hasta ahora, los esfuerzos regulatorios no han reducido los efectos letales de las actividades humanas sobre las ballenas a nivel de población, aunque no excluimos la posibilidad de éxito de medidas enfocadas a hábitats locales específicos que no estuvieron dentro de la resolución de nuestro análisis. No es claro como se relacionan con nuestros resultados las deficiencias en el diseño o implementación del manejo. Análisis como el que realizamos son cruciales para la evaluación crítica de decisiones para el manejo de vida silvestre, y los resultados de estos análisis pueden proporcionar directrices a los manejadores para que modifiquen medidas regulatorias y puedan ser aplicadas globalmente en temas de conservación relacionadas con mortalidad. PMID:23025354

Systematically frameshifting by deletion of every 4th or 4th and 5th nucleotides during mitochondrial transcription: RNA self-hybridization regulates delRNA expression.

PubMed

Seligmann, Hervé

2016-01-01

In mitochondria, secondary structures punctuate post-transcriptional RNA processing. Recently described transcripts match the human mitogenome after systematic deletions of every 4th, respectively every 4th and 5th nucleotides, called delRNAs. Here I explore predicted stem-loop hairpin formation by delRNAs, and their associations with delRNA transcription and detected peptides matching their translation. Despite missing 25, respectively 40% of the nucleotides in the original sequence, del-transformed sequences form significantly more secondary structures than corresponding randomly shuffled sequences, indicating biological function, independently of, and in combination with, previously detected delRNA and thereof translated peptides. Self-hybridization decreases delRNA abundances, indicating downregulation. Systematic deletions of the human mitogenome reveal new, unsuspected coding and structural informations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pleistocene Variations in Delivery and Deposition of Organic Matter Under the Benguela Current Upwelling System - Biomarker Isotopic Evidence From Sediment Light-Dark Color Cycles

NASA Astrophysics Data System (ADS)

Meyers, P. A.; Bouloubassi, I.; Pancost, R. D.; Robinson, R. S.

2007-12-01

The light-dark color cycles that are distinctive features of sediment beneath the Benguela Current Upwelling System imply repetitive alternations in organic matter delivery and deposition. Organic geochemical proxies for paleoproductivity and for depositional conditions were employed to investigate the paleoceanographic processes involved in creating these cycles in two sediment sequences from ODP Site 1084 corresponding to 0.7 and 1.1 Mya. Concentrations of total organic carbon (TOC) vary between 3.5 and 17.1 wt percent, and those of calcium carbonate fluctuate inversely between 68 and 1 percent, suggesting that carbonate dissolution is involved with the light-dark cycles. Bulk organic del 13C and del 15N values that remain constant across the two light-dark sediment intervals indicate that the extent of nutrient utilization did not change in each cycle. Biomarker compositions in both sequences reflect a range of organic matter sources. Abundant n-alkanes and n-alkanols with odd-over-even and even-over-odd distributions, respectively, record land-plant inputs. Other terrestrial biomakers (e.g triterpenoid acids and alcohols) are present but in very low abundances, suggesting that the n- alkyl components derive predominantly from eolian inputs. Carbon isotopic values of n-alkanes range from -25 to -28 permil, suggesting a mixture of C3 and C4 sources. In contrast, n-alkanol isotopic compositions range from -28 to -34 permil, suggesting that they derive solely from C3 plants. Algal biomarkers are abundant and diverse, represented by 1,15-C30 diols (eustigmatophytes), 4-desmethyl and -methylsterols (diatoms, dinoflagellates), and alkenones (haptophytes). These compounds all have del 13C values ranging from ca. -22 to -24 permil, consistent with a marine origin. Systematic differences in isotopic values imply that marine productivity at 1.1 Mya was higher than at 0.7 Mya, but alkenone-based sea-surface temperatures are higher at 1.1 Mya (21 deg) than at 0.7 Mya (15 deg), which indicates that changes in water-mass properties were also involved.

F-35 Force Development Evaluation and Weapons School Beddown Environmental Impact Statement

DTIC Science & Technology

2011-05-01

deficiencias encontradas después del despliegue del sistema; ♦ explora medios no materiales (por ejemplo, tácticas) para satisfacer requisitos...del adecuado desempeño del avión en combate al proporcionar entrenamiento, información sobre las capacidades operativas y nuevos requisitos. Además

Perk Ablation Ameliorates Myelination in S63del-Charcot–Marie–Tooth 1B Neuropathy

PubMed Central

Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D’Antonio, Maurizio; Feltri, Maria L.

2016-01-01

In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot–Marie–Tooth disease type 1B (CMT1B)–S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment: Perk haploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/− compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition, Perk deficiency in other cells may contribute to demyelination in a non–Schwann-cell autonomous manner. PMID:27095827

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

PubMed Central

McGraw, K L; Zhang, L M; Rollison, D E; Basiorka, A A; Fulp, W; Rawal, B; Jerez, A; Billingsley, D L; Lin, H-Y; Kurtin, S E; Yoder, S; Zhang, Y; Guinta, K; Mallo, M; Solé, F; Calasanz, M J; Cervera, J; Such, E; González, T; Nevill, T J; Haferlach, T; Smith, A E; Kulasekararaj, A; Mufti, G; Karsan, A; Maciejewski, J P; Sokol, L; Epling-Burnette, P K; Wei, S; List, A F

2015-01-01

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis. PMID:25768405

PubMed

Martínez Carrión, José Miguel; Cámara, Antonio D; Pérez-Castroviejo, Pedro María

2016-12-12

Objetivo: analizar la geografía del estado nutricional en España y su evolución entre mediados del siglo xixy comienzos del siglo xx, etapa previa a la transición nutricional con alta prevalencia de malnutrición.Métodos: se utilizan datos antropométricos agregados (promedios provinciales de estatura) del reclutamiento militar en 1858 y 1913, así como promedios provinciales de estatura y peso procedentes de una revisión realizada entre 119.571 soldados en 1903-1906. Con estos datos se elaboran cartografía y estadísticos descriptivos.Resultados: los parámetros antropométricos de los españoles se situaban entre los valores de complexión más bajos de Europa antes de la transición nutricional. Entre 1858 y 1913, la altura media creció solo 1,43 cm. En ese periodo hubo cambios significativos en la geografía antropométrica marcados por la configuración de una polaridad nutricional a las puertas de la I Guerra Mundial: las provincias del centro y del sur de país exhiben mayor incidencia de la malnutrición crónica que las provincias del arco Noreste, que disfrutan de ventaja relativa en términos nutricionales.Conclusión:las desigualdades territoriales que configuraron una geografía polarizada del estado nutricional en España pueden asociarse en parte a los cambios ambientales del periodo, caracterizados por el inicio de la modernización y la industrialización y, asimismo, por la privación derivada de las crisis agrarias, las enfermedades y el relativo atraso tecnológico. Se destaca la relevancia de la historia antropométrica para el estudio de los niveles de vida en poblaciones del pasado y del proceso de transición nutricional.

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations.

PubMed

Dusatkova, Petra; Pfäffle, Roland; Brown, Milton R; Akulevich, Natallia; Arnhold, Ivo J P; Kalina, Maria A; Kot, Karolina; Krzisnik, Ciril; Lemos, Manuel C; Malikova, Jana; Navardauskaite, Ruta; Obermannova, Barbora; Pribilincova, Zuzana; Sallai, Agnes; Stipancic, Gordana; Verkauskiene, Rasa; Cinek, Ondrej; Blum, Werner F; Parks, John S; Austerlitz, Frederic; Lebl, Jan

2016-03-01

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations

PubMed Central

Dusatkova, Petra; Pfäffle, Roland; Brown, Milton R; Akulevich, Natallia; Arnhold, Ivo JP; Kalina, Maria A; Kot, Karolina; Krzisnik, Ciril; Lemos, Manuel C; Malikova, Jana; Navardauskaite, Ruta; Obermannova, Barbora; Pribilincova, Zuzana; Sallai, Agnes; Stipancic, Gordana; Verkauskiene, Rasa; Cinek, Ondrej; Blum, Werner F; Parks, John S; Austerlitz, Frederic; Lebl, Jan

2016-01-01

Two variants (c.[301_302delAG][301_302delAG] and c.[150delA][150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG][301_302delAG] or c.[150delA][150delA] or c.[301_302delAG][ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations – a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants – c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1–116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1–29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2–17.0) and 16.4 (14.4–20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4–52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants. PMID:26059845

Association of methylenetetrahydrofolate reductase (MTHFR 677C>T) and thymidylate synthase (TSER and TS 1494del6) polymorphisms with premature ovarian failure in Korean women.

PubMed

Rah, HyungChul; Jeon, Young Joo; Choi, Youngsok; Shim, Sung Han; Yoon, Tae Ki; Choi, Dong Hee; Cha, Sun Hee; Kim, Nam Keun

2012-11-01

The aim of our study was to investigate whether methylenetetrahydrofolate reductase (MTHFR) gene variant (MTHFR 677C>T) and thymidylate synthase (TS) gene variants (TS enhancer region [TSER] and TS 1494del6) confer a risk for premature ovarian failure (POF). We genotyped 136 POF patients and 236 controls among Korean women for the three single nucleotide polymorphism sites using polymerase chain reaction restriction fragment length polymorphism analysis. Differences in the MTHFR 677C>T, TSER, and TS 1494del6 genotype frequencies between POF patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as a measure of the strength of the association between genotypes and POF. The MTHFR 677CT and CT + TT variant genotypes were more frequent in POF patients than in controls (OR, 2.249; 95% CI, 1.317-3.843; and OR, 2.132; 95% CI, 1.268-3.585, respectively). The combined genotype frequencies of MTHFR 677CT + TT/TSER 3R3R and 677CT + TT/TS 1494del6 del6/del6 were higher in patients than in controls (OR, 2.300; 95% CI, 1.219-4.337; and OR, 3.314; 95% CI, 1.623-6.767, respectively). The T-3R-del6 and T-2R-del6 (MTHFR 677C>T/TSER/TS 1494del6) haplotypes were more frequent in patients (OR, 1.450; 95% CI, 1.050-2.002; and OR, 2.911; 95% CI, 1.191-7.117, respectively), whereas the C-2R-del6 haplotype was less frequent in patients (OR, 0.372; 95% CI, 0.152-0.912). The T-del6 (MTHFR 677/TS 1494del6) haplotype frequency was higher among patients (OR, 1.653; 95% CI, 1.206-2.266), whereas the C-del6 haplotype frequency was lower among patients (OR, 0.700; 95% CI, 0.516-0.950). We did not find an association between TSER or TS 1494del6 polymorphisms and POF. Our data suggest that the MTHFR 677T allele may increase the risk for POF, which could lead to the development of novel genetic markers for predicting the risk of POF in patients.

Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications.

PubMed

Muranen, Taru A; Greco, Dario; Fagerholm, Rainer; Kilpivaara, Outi; Kämpjärvi, Kati; Aittomäki, Kristiina; Blomqvist, Carl; Heikkilä, Päivi; Borg, Ake; Nevanlinna, Heli

2011-09-20

Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels.Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified potential drivers of CHEK2 1100delC-associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene-expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of the CHEK2 1100delC mutation.

Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications

PubMed Central

2011-01-01

Introduction Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. Methods In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. Results We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels. Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified potential drivers of CHEK2 1100delC-associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene-expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of the CHEK2 1100delC mutation. PMID:21542898

PRPF3-Associated Autosomal Dominant Retinitis Pigmentosa and CYP4V2-Associated Bietti's Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family.

PubMed

Meng, Xiaohong; Li, Qiyou; Guo, Hong; Xu, Haiwei; Li, Shiying; Yin, Zhengqin

2017-01-01

To characterize the clinical and molecular genetic characteristics of a large, multigenerational Chinese family showing different phenotypes. A pedigree consisted of 56 individuals in 5 generations was recruited. Comprehensive ophthalmic examinations were performed in 16 family members affected. Mutation screening of CYP4V2 was performed by Sanger sequencing. Next-generation sequencing (NGS) was performed to capture and sequence all exons of 47 known retinal dystrophy-associated genes in two affected family members who had no mutations in CYP4V2 . The detected variants in NGS were validated by Sanger sequencing in the family members. Two compound heterozygous CYP4V2 mutations (c.802-8_810del17insGC and c.992A>C) were detected in the proband who presented typical clinical features of BCD. One missense mutation (c.1482C>T, p.T494M) in the PRPF3 gene was detected in 9 out of 22 affected family members who manifested classical clinical features of RP. Our results showed that two compound heterozygous CYP4V2 mutations caused BCD, and one missense mutation in PRPF3 was responsible for adRP in this large family. This study suggests that accurate phenotypic diagnosis, molecular diagnosis, and genetic counseling are necessary for patients with hereditary retinal degeneration in some large mutigenerational family.

Recent advances on the encoding and selection methods of DNA-encoded chemical library.

PubMed

Shi, Bingbing; Zhou, Yu; Huang, Yiran; Zhang, Jianfu; Li, Xiaoyu

2017-02-01

DNA-encoded chemical library (DEL) has emerged as a powerful and versatile tool for ligand discovery in chemical biology research and in drug discovery. Encoding and selection methods are two of the most important technological aspects of DEL that can dictate the performance and utilities of DELs. In this digest, we have summarized recent advances on the encoding and selection strategies of DEL and also discussed the latest developments on DNA-encoded dynamic library, a new frontier in DEL research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing the Cytotoxicity of Black Carbon As A Model for Ultrafine Anthropogenic Aerosol Across Human and Murine Cells: A Chronic Exposure Model of Nanosized Particulate Matter

NASA Astrophysics Data System (ADS)

Salinas, E.

2015-12-01

Combustion-derived nanomaterials or ultrafine (<1 μm) atmospheric aerosols are primarily products of anthropogenic activities, such as the burning of fossil fuels. Ultrafine particles (UFPs) can absorb other noxious pollutants including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), toxic organic compounds, and heavy metals. The combination of high population density, meteorological conditions, and industrial productivity brings high levels of air pollution to the metropolitan area of El Paso, Texas, USA/ Ciudad Juarez, Chihuahua, Mexico, comprising the Paso del Norte air basin. A study conducted by scientists from the Research Triangle Park in North Carolina, analyzed sites adjacent to heavy-traffic highways in El Paso and elucidated higher UFP concentrations in comparison to previously published work exploring pollution and adverse health effects in the basin. UFPs can penetrate deep into the alveolar sacs of the lung, reaching distant alveolar sacs and inducing a series of immune responses that are detrimental to the body: evidence suggests that UFPs can also cross the alveolar-blood barrier and potentially endanger the body's immune response. The physical properties of UFPs and the dynamics of local atmospheric and topographical conditions indicate that emissions of nanosized carbonaceous aerosols could pose significant threats to biological tissues upon inhalation by local residents of the Paso del Norte. This study utilizes Black Carbon (BC) as a model for environmental UFPs and its effects on the immunological response. An in vitro approach is used to measure the ability of BC to promote cell death upon long-term exposure. Human epithelial lung cells (A549), human peripheral-blood monocytes (THP-1), murine macrophages (RAW264.7), and murine epithelial lung cells (LA-4) were treated with BC and assessed for metabolic activity after chronic exposure utilizing three distinct and independent cell viability assays. The cell viability experiments included a chronic study at 7, 10, and 14 days of UFP exposure at six different concentrations of BC: 100μM, 300μM, 600μM, 1,250μM, 2,500μM, and 5,000μM conducting the Trypan Blue (TB) Exclusion Assay, Calcein-AM Viability Assay, and CellTiter-Glo Viability Assay.

Groundwater drainage from fissures as a source for lahars

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

Johnson, P. J.; Valentine, G. A.; Stauffer, P. H.

One mechanism for generating lahars at volcanoes experiencing unrest is the disruption of internal aquifers. These disruptions can trigger releases of large quantities of groundwater. An example of such aquifer disruption occurred at Nevado del Huila Volcano, Colombia, during February and April 2007 when large fractures formed across the summit area of the volcano and lahars were emitted from them. Previous work interpreted that lahar volumes could not be accounted for by melted glacial snow or precipitation, and by elimination suggested that the primary water source was groundwater. Conceptual models have been developed for perched, confined aquifers that have beenmore » heated and pressurized by magma intrusions, followed by sudden pressure release and water emission during fracture formation. In this paper, we consider an alternative end member wherein water release from large fissures at volcanoes is driven by simple gravity drainage. We apply numerical modeling to quantify water discharge from the porous medium surrounding a fissure with a low-elevation free exit. If a long fracture with high vertical extent (on the order of hundreds of meters) intersects a highly connected saturated porous medium, large volumes (on order 10 3 m 3/m of crack length) of water may be released within tens of minutes. The drainage rates from the model may be adequate to account for the Nevado del Huila events if the medium surrounding the crack contains a large volume of water and has high horizontal permeability. Finally, this simple but poorly understood mechanism can present a hazard on its own or compound other processes releasing water from volcanoes.« less

Molecular Characteristics, Clinical and Immunologic Manifestations of 11 Children with Omenn Syndrome in East Slavs (Russia, Belarus, Ukraine).

PubMed

Sharapova, Svetlana O; Guryanova, Irina E; Pashchenko, Olga E; Kondratenko, Irina V; Kostyuchenko, Larisa V; Rodina, Yulia A; Varlamova, Tatjana V; Bondarenko, Anastasiia V; Chernyshova, Liudmyla I; Gyseva, Marina N; Belevtsev, Mikhail V; Minakovskaya, Nina V; Aleinikova, Olga V

2016-01-01

Omenn syndrome [Mendelian Inheritance (OMIM 603554)] is a genetic disease of the immune system, characterized by the presence of fatal generalized severe erythroderma, lymphoadenopathy, eosinophilia and profound immunodeficiency. We studied clinical and immunologic presentation of the disease manifestation among East Slavs population with genetically confirmed Omenn syndrome. We collected clinical and immunologic data of 11 patients (1 from Belarus, 5--Ukraine, 5--Russia): 6 females, 5 males. The age of Omenn syndrome manifestation varied from the 1st day of life to 1 year and 1 month, the age of diagnosis--20 days to 1 year and 10 months. Nine out of 11 patients had classic immunologic phenotype T(+/-)B-NK+, 1 pt had TlowB + NK+ with CD3 + TCRgd + expansion and 1 had TlowB+/-NK+ phenotype. Eight out of 11 pts had mutation in RAG1 gene, 4 out of 8 had c.368-369delAA (p.K86fsX118) in homozygous state or heterozygous compound. In our cohort of patients, we also described two new mutations in RAG genes (p.E722Q in RAG1 and p.M459R in RAG2). At present, 7/11 were transplanted and 5 out of the transplanted are alive. This study demonstrates that the most popular genetic abnormality in East Slavs children with Omenn syndrome is c.368-369delAA (p.K86fs118) in RAG1 gene, which may be connected with more favorable prognosis because 4/4 patients survived after hematopoietic stem cells transplantation.

Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

PubMed Central

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905

Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria.

PubMed

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R; Gray, Amie K; Baluarte, H Jorge; Econs, Michael J

2014-02-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440-1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. © 2013.

Groundwater drainage from fissures as a source for lahars

NASA Astrophysics Data System (ADS)

Johnson, P. J.; Valentine, G. A.; Stauffer, P. H.; Lowry, C. S.; Sonder, I.; Pulgarín, B. A.; Santacoloma, C. C.; Agudelo, A.

2018-04-01

One mechanism for generating lahars at volcanoes experiencing unrest is the disruption of internal aquifers. These disruptions can trigger releases of large quantities of groundwater. An example of such aquifer disruption occurred at Nevado del Huila Volcano, Colombia, during February and April 2007 when large fractures formed across the summit area of the volcano and lahars were emitted from them. Previous work interpreted that lahar volumes could not be accounted for by melted glacial snow or precipitation, and by elimination suggested that the primary water source was groundwater. Conceptual models have been developed for perched, confined aquifers that have been heated and pressurized by magma intrusions, followed by sudden pressure release and water emission during fracture formation. We consider an alternative end member wherein water release from large fissures at volcanoes is driven by simple gravity drainage. We apply numerical modeling to quantify water discharge from the porous medium surrounding a fissure with a low-elevation free exit. If a long fracture with high vertical extent (on the order of hundreds of meters) intersects a highly connected saturated porous medium, large volumes (on order 103 m3/m of crack length) of water may be released within tens of minutes. The drainage rates from the model may be adequate to account for the Nevado del Huila events if the medium surrounding the crack contains a large volume of water and has high horizontal permeability. This simple but poorly understood mechanism can present a hazard on its own or compound other processes releasing water from volcanoes.

Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome.

PubMed

Blackburn, Patrick R; Xu, Zhi; Tumelty, Kathleen E; Zhao, Rose W; Monis, William J; Harris, Kimberly G; Gass, Jennifer M; Cousin, Margot A; Boczek, Nicole J; Mitkov, Mario V; Cappel, Mark A; Francomano, Clair A; Parisi, Joseph E; Klee, Eric W; Faqeih, Eissa; Alkuraya, Fowzan S; Layne, Matthew D; McDonnell, Nazli B; Atwal, Paldeep S

2018-04-05

AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 -/- mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581 ∗ ]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs ∗ 3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Groundwater drainage from fissures as a source for lahars

DOE PAGES

Johnson, P. J.; Valentine, G. A.; Stauffer, P. H.; ...

2018-03-22

One mechanism for generating lahars at volcanoes experiencing unrest is the disruption of internal aquifers. These disruptions can trigger releases of large quantities of groundwater. An example of such aquifer disruption occurred at Nevado del Huila Volcano, Colombia, during February and April 2007 when large fractures formed across the summit area of the volcano and lahars were emitted from them. Previous work interpreted that lahar volumes could not be accounted for by melted glacial snow or precipitation, and by elimination suggested that the primary water source was groundwater. Conceptual models have been developed for perched, confined aquifers that have beenmore » heated and pressurized by magma intrusions, followed by sudden pressure release and water emission during fracture formation. In this paper, we consider an alternative end member wherein water release from large fissures at volcanoes is driven by simple gravity drainage. We apply numerical modeling to quantify water discharge from the porous medium surrounding a fissure with a low-elevation free exit. If a long fracture with high vertical extent (on the order of hundreds of meters) intersects a highly connected saturated porous medium, large volumes (on order 10 3 m 3/m of crack length) of water may be released within tens of minutes. The drainage rates from the model may be adequate to account for the Nevado del Huila events if the medium surrounding the crack contains a large volume of water and has high horizontal permeability. Finally, this simple but poorly understood mechanism can present a hazard on its own or compound other processes releasing water from volcanoes.« less

Growth Inhibition and DNA Damage Induced by X-Phenols in Yeast: A Quantitative Structure–Activity Relationship Study

PubMed Central

2017-01-01

Phenolic compounds and their derivatives are ubiquitous constituents of numerous synthetic and natural chemicals that exist in the environment. Their toxicity is mostly attributed to their hydrophobicity and/or the formation of free radicals. In a continuation of the study of phenolic toxicity in a systematic manner, we have examined the biological responses of Saccharomyces cerevisiae to a series of mostly monosubstituted phenols utilizing a quantitative structure–activity relationship (QSAR) approach. The biological end points included a growth assay that determines the levels of growth inhibition induced by the phenols as well as a yeast deletion (DEL) assay that assesses the ability of X-phenols to induce DNA damage or DNA breaks. The QSAR analysis of cell growth patterns determined by IC50 and IC80 values indicates that toxicity is delineated by a hydrophobic, parabolic model. The DEL assay was then utilized to detect genomic deletions in yeast. The increase in the genotoxicity was enhanced by the electrophilicity of the phenolic substituents that were strong electron donors as well as by minimal hydrophobicity. The electrophilicities are represented by Brown’s sigma plus values that are a variant of the Hammett sigma constants. A few mutant strains of genes involved in DNA repair were separately exposed to 2,6-di-tert-butyl-4-methyl-phenol (BHT) and butylated hydroxy anisole (BHA). They were subsequently screened for growth phenotypes. BHA-induced growth defects in most of the DNA repair null mutant strains, whereas BHT was unresponsive. PMID:29302629

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

PubMed Central

Huijts, Petra EA; Hollestelle, Antoinette; Balliu, Brunilda; Houwing-Duistermaat, Jeanine J; Meijers, Caro M; Blom, Jannet C; Ozturk, Bahar; Krol-Warmerdam, Elly MM; Wijnen, Juul; Berns, Els MJJ; Martens, John WM; Seynaeve, Caroline; Kiemeney, Lambertus A; van der Heijden, Henricus F; Tollenaar, Rob AEM; Devilee, Peter; van Asperen, Christi J

2014-01-01

The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4–32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency. PMID:23652375

The -2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion.

PubMed

Hashemi, Mohammad; Danesh, Hiva; Bizhani, Fatemeh; Mokhtari, Mojgan; Bahari, Gholamreza; Tabasi, Farhad; Taheri, Mohsen

2018-03-01

Recurrent spontaneous abortion (RSA) is a common health problem affecting women of reproductive age. Altered expression of vascular endothelial growth factor ( VEGF ) has been associated with spontaneous abortion. The present case-control study aimed to evaluate the impact of the 18-bp insertion/deletion (ins/del) polymorphism (rs35569394) in the promoter region of the VEGF gene on idiopathic RSA. Genomic DNA from 93 patients with RSA and 93 healthy fertile women of southeastern Iran was isolated using the salting-out method. Genotyping of the rs35569394 variant was performed by a polymerase chain reaction (PCR) method. The findings indicated that the VEGF 18-bp ins/del variant significantly increased the risk of RSA under codominant (ins/ins vs. del/del; OR=2.85, 95% CI=1.31-6.22, P=0.019), dominant (del/ins+ins/ins vs. del/del; OR=2.19, 95% CI=1.20-4.01, P=0.015) and allelic (ins vs. del; OR=1.90, 95% CI=1.25-2.88, P=0.003) inheritance models. In summary, the findings propose a significant association between the VEGF 18-bp ins/del polymorphism and risk of RSA in a sample of the southeast Iranian population. Further studies on larger sample sizes and different ethnicities are required to validate the present findings.

Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies.

PubMed

Bello, Luca; Campadello, Paola; Barp, Andrea; Fanin, Marina; Semplicini, Claudio; Sorarù, Gianni; Caumo, Luca; Calore, Chiara; Angelini, Corrado; Pegoraro, Elena

2016-09-01

We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.

Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.

PubMed

Nagel, Jord H A; Peeters, Justine K; Smid, Marcel; Sieuwerts, Anieta M; Wasielewski, Marijke; de Weerd, Vanja; Trapman-Jansen, Anita M A C; van den Ouweland, Ans; Brüggenwirth, Hennie; van I Jcken, Wilfred F J; Klijn, Jan G M; van der Spek, Peter J; Foekens, John A; Martens, John W M; Schutte, Mieke; Meijers-Heijboer, Hanne

2012-04-01

CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. In line with previous work, all CHEK2 1100delC mutant tumors clustered among the hormone receptor-positive breast cancers. In the hormone receptor-positive subset, a 40-gene CHEK2 signature was subsequently defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.

Unidades del paisaje de Puerto Rico: la influencia del clima, el substrato y la topografia

Treesearch

William Gould; Michael E. Jimenez; Gary Potts; Maya Quinones; Sebastian Martinuzzi

2008-01-01

El mapa de unidades del paisaje de Puerto Rico representa variaciones climaticas, topograficas y del substrato mediante la integracion de seis zonas climaticas (Ewel y Whitmore, 1973), seis substratos (Bawiec, 2001; USGS, 2005), cinco posiciones topograficas, o topoformas (Martinuzzi et al. 2007), y cuerpos de agua (USGS 2005). Los substratos representan el conjunto...

Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

PubMed

Prodhan, P; Gossett, J M; Rycus, P T; Gupta, P

2015-11-01

The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children <18 years undergoing heart surgery for either common atrio-ventricular canal, tetralogy of Fallot, truncus arteriosus or transposition of the great vessels and interrupted aortic arch and requiring ECMO, from 1998-2011. The outcomes evaluated included mortality, ECMO duration and length of hospital stay in patients with del22q11 syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls. © The Author(s) 2015.

Percepcion de los profesores universitarios acerca del concepto cultura cientifica y de sus implicaciones en el nuevo bachillerato del Recinto de Rio Piedras de la Universidad de Puerto Rico

NASA Astrophysics Data System (ADS)

Ramos Pastrana, Nilsa

El Senado Academico del Recinto de Rio Piedras de la Universidad de Puerto Rico aprobo en el ano academico 2005-2006 la Certificacion 46, que contiene los lineamientos de un nuevo bachillerato. Este nuevo bachillerato introdujo cambios significativos en el curriculo tradicional. Entre ellos se encuentra la reduccion del componente de educacion general y el de Ciencias Biologicas en particular. La reduccion de creditos en el componente de Ciencias Biologicas ha obligado a reevaluar el concepto de cultura cientifica que desarrollan esos cursos. El proposito del estudio consistio en auscultar las percepciones de los profesores de las Facultades de Administracion de Empresas, Humanidades, Ciencias Sociales, Ciencias Naturales, Educacion y Estudios Generales del Recinto de Rio Piedras de la Universidad de Puerto Rico en torno al concepto de cultura cientifica, los contenidos disciplinares del curso de Ciencias Biologicas y la reduccion de creditos en el nuevo bachillerato. Las preguntas que guiaron la investigacion fueron: ¿cuales son las percepciones que tienen los profesores de las Facultades de Administracion de Empresas, Ciencias Sociales, Estudios Generales, Ciencias Naturales, Humanidades y Educacion, en torno al concepto de cultura cientifica y los contenidos disciplinares del curso de Ciencias Biologicas? ¿cuales son las percepciones que tienen los profesores de Ciencias Biologicas en torno al concepto cultura cientifica y los contenidos disciplinares del curso de Ciencias Biologicas? ¿existen diferencias significativas por facultad, genero, experiencia, rango y nombramiento en las percepciones que tienen los profesores del Recinto de Rio Piedras de la Universidad de Puerto Rico sobre los elementos que caracterizan la cultura cientifica y los contenidos biologicos que deben tener los egresados del Recinto? ¿que implicaciones curriculares tienen estos testimonios en el desarrollo del concepto de cultura cientifica en el nuevo bachillerato? Para realizar la investigacion se utilizo una metodologia cuantitativa y la herramienta para lograrlo fue una encuesta. La encuesta se analizo estadisticamente mediante analisis de frecuencias y por cientos, prueba ANOVA, prueba t, pruebas Post Hoc de Tukey y de Levene. Tambien se realizo nuevamente una prueba de confiabilidad mediante el alfa de Cronbach. Los resultados reflejaron que los profesores de las Facultades de Administracion de Empresas, Ciencias Sociales, Ciencias Naturales, Educacion, Humanidades, Estudios Generales y el Departamento de Ciencias Biologicas tienen una percepcion muy positiva del concepto de cultura cientifica, los contenidos curriculares de Ciencias Biologicas y del nuevo bachillerato.

Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic mechanisms but equivalent poorer clinical outcome.

PubMed

Puiggros, Anna; Venturas, Marta; Salido, Marta; Blanco, Gonzalo; Fernandez-Rodriguez, Concepción; Collado, Rosa; Valiente, Alberto; Ruiz-Xivillé, Neus; Carrió, Ana; Ortuño, Francisco José; Luño, Elisa; Calasanz, María José; Ardanaz, María Teresa; Piñán, María Ángeles; Talavera, Elisabet; González, María Teresa; Ortega, Margarita; Marugán, Isabel; Ferrer, Ana; Gimeno, Eva; Bellosillo, Beatriz; Delgado, Julio; Hernández, José Ángel; Hernández-Rivas, Jesús María; Espinet, Blanca

2014-09-01

Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G-banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F-del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i-del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i-del(13q) was shorter than F-del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q-deleted CLL patients associated with a worse clinical outcome. © 2014 Wiley Periodicals, Inc.

El Alcalde José Carlos Aponte Dalmau del Municipio de Carolina es nombrado a formar parte del Comité Asesor de Gobiernos Locales de la EPA a nivel de todos los Estados Unidos

EPA Pesticide Factsheets

Comunicado de prensa de la EPA: El Alcalde José Carlos Aponte Dalmau del Municipio de Carolina es nombrado a formar parte del Comité Asesor de Gobiernos Locales de la EPA a nivel de todos los Estados Unidos

Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases.

PubMed

Adank, Muriel A; Verhoef, Senno; Oldenburg, Rogier A; Schmidt, Marjanka K; Hooning, Maartje J; Martens, John W M; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I; Jonker, Marianne A; Meijers-Heijboer, Hanne

2013-05-01

The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n=2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown. Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p<0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p=0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p=0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p=0.025). There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2∗1100delC familial breast cancer relatives. Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs. Copyright © 2013 Elsevier Ltd. All rights reserved.

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

PubMed Central

Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Corrales-Rodriguez, Luis; Martín, Claudio; Reguart, Noemí; Archila, Pilar; Rodríguez, July; Cuello, Mauricio; Ortíz, Carlos; Franco, Sandra; Rolfo, Christian; Rosell, Rafael

2016-01-01

Background Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. Results BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). Methods We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. Conclusions The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation. PMID:27926478

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations.

PubMed

Cardona, Andrés F; Rojas, Leonardo; Wills, Beatriz; Arrieta, Oscar; Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Corrales-Rodriguez, Luis; Martín, Claudio; Reguart, Noemí; Archila, Pilar; Rodríguez, July; Cuello, Mauricio; Ortíz, Carlos; Franco, Sandra; Rolfo, Christian; Rosell, Rafael; on behalf of the CLICaP

2016-09-19

Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.

Distinct Purine Distribution in Carbonaceous Chondrites

NASA Technical Reports Server (NTRS)

Callahan, Michael P.; Smith, Karen E.; Cleaves, Henderson J.; Ruzicka, Josef; Stern, Jennifer C.; Glavin, Daniel P.; House, Christopher H.; Dworkin, Jason P.

2011-01-01

Carbonaceous chondrite meteorites are known to contain a diverse suite of organic compounds, many of which are essential components of biochemistry. Amino acids, which are the monomers of proteins, have been extensively studied in such meteorites (e.g. Botta and Bada 2002; Pizzarello et aI., 2006). The origin of amino acids in meteorites has been firmly established as extraterrestrial based on their detection typically as racemic mixtures of amino acids, the presence of many non-protein amino acids, and non-terrestrial values for compound-specific deuterium, carbon, and nitrogen isotopic measurements. In contrast to amino acids, nucleobases in meteorites have been far less studied. Nucleobases are substituted one-ring (pyrimidine) or two-ring (purine) nitrogen heterocyclic compounds and serve as the information carriers of nucleic acids and in numerous coenzymes. All of the purines (adenine, guanine, hypoxanthine, and xanthine) and pyrimidines (uracil) previously reported in meteorites are biologically common and could be interpreted as the result of terrestrial contamination (e.g. van del' Velden and Schwartz, 1974.) Unlike other meteoritic organics, there have been no observations of stochastic molecular diversity of purines and pyrimidines in meteorites, which has been a criterion for establishing extraterrestrial origin. Maltins et al. (2008) performed compound-specific stable carbon isotope measurements for uracil and xanthine in the Murchison meteorite. They assigned a non-terrestrial origin for these nucleobases; however, the possibility that interfering indigenous molecules (e.g. carboxylic acids) contributed to the 13C-enriched isotope values for these nucleobases cannot be completely ruled out. Thus, the origin of these meteoritic nucleobases has never been established unequivocally. Here we report on our investigation of extracts of II different carbonaceous chondrites covering various petrographic types (Cl, CM, and CR) and degrees of aqueous alteration (l, 2, and 3) and one ureilite. Analysis via liquid chromatography coupled with electrospray triple-stage mass spectrometry or orbitrap mass spectrometry employed a targeted approach for analysis focused on the five canonical RNA/DNA nucleobases as well as 14 non-canonical pyrimidines and purines, which have bcen observed under plausible prebiotic reactions.

Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis

PubMed Central

Traivaree, Chanchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Prasertsin, Warakorn; Boonyawat, Boonchai

2018-01-01

Introduction Beta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM). Objective This study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital. Materials and methods Seventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection. Results All 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (<3rd percentile) compared to compound heterozygous beta-thalassemia patients (25–50th percentile). Conclusion This study revealed a genotype–phenotype correlation of the most prevalent beta-thalassemia in Thai children using diagnostic capacity in genotypic analysis of HBB mutation. Our findings can provide a better prediction of clinical manifestation and severity by early identification of the type of the HBB mutations. PMID:29695942

Expression of exon-8-skipped kindlin-1 does not compensate for defects of Kindler syndrome.

PubMed

Natsuga, Ken; Nishie, Wataru; Shinkuma, Satoru; Nakamura, Hideki; Matsushima, Yoichiro; Tatsuta, Aya; Komine, Mayumi; Shimizu, Hiroshi

2011-01-01

Kindler syndrome (KS) is a rare, inherited skin disease characterized by blister formation and generalized poikiloderma. Mutations in KIND1, which encodes kindlin-1, are responsible for KS. c.1089del/1089+1del is a recurrent splice-site deletion mutation in KS patients. To elucidate the effects of c.1089del/1089+1del at the mRNA and protein level. Two KS patients with c.1089del/1089+1del were included in this study. Immunofluorescence analysis of KS skin samples using antibodies against the dermo-epidermal junction proteins was performed. Exon-trapping experiments were performed to isolate the mRNA sequences transcribed from genomic DNA harbouring c.1089del/1089+1del. β1 integrin activation in HeLa cells transfected with truncated KIND1 cDNA was analyzed. Immunofluorescence study showed positive expression of kindlin-1 in KS skin with c.1089del/1089+1del mutation. We identified the exon-8-skipped in-frame transcript as the main product among multiple splicing variants derived from that mutation. HeLa cells transfected with KIND1 cDNA without exon 8 showed impaired β1 integrin activation. Exon-8-coding amino acids are located in the FERM F2 domain, which is conserved among species, and the unstructured region between F2 and the pleckstrin homology domain. This study suggests that exon-8-skipped truncated kindlin-1 is functionally defective and does not compensate for the defects of KS, even though kindlin-1 expression in skin is positive. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Max Brödel: his art, legacy, and contributions to neurosurgery through medical illustration.

PubMed

Patel, Smruti K; Couldwell, William T; Liu, James K

2011-07-01

Max Brödel is considered the father of modern medical illustration. This report reviews his contributions to neurosurgery as a medical illustrator. Max Brödel, a young artist from Leipzig, Germany, was hired at Johns Hopkins Hospital in 1894, where he illustrated an operative textbook of gynecology for Howard A. Kelly. Although Brödel did not have any formal medical training, he quickly acquired knowledge of anatomy, pathology, physiology, and surgery. Brödel's extraordinary illustrations were characterized by an aerial perspective that conveyed the surgeon's operative viewpoint and precise surgical anatomy. He masterfully incorporated tissue realism with cross-sectional anatomy to accentuate concepts while maintaining topographical accuracy. Brödel's reputation spread quickly and resulted in collaborations with prominent surgeons, such as Cushing, Halsted, and Dandy. Cushing, who also possessed artistic talent, became a pupil of Brödel and remained a very close friend. In 1911, Brödel was appointed the director of the Department of Art as Applied to Medicine at Johns Hopkins, the first academic department of its kind in the world. For the next several decades, he trained generations of renowned medical illustrators. Just as Osler, Halsted, and Cushing passed their skills and knowledge to future leaders of medicine and surgery, Brödel did the same for the field of medical illustration. The advancement of neurosurgical education has been greatly facilitated by Max Brödel's artistic contributions. His unique ability to synthesize art and medicine resulted in timeless illustrations that remain indispensable to surgeons. The art produced by his legacy of illustrators continues to flourish in neurosurgical literature today.

Doping test results dependent on genotype of uridine diphospho-glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation.

PubMed

Schulze, Jenny Jakobsson; Lundmark, Jonas; Garle, Mats; Skilving, Ilona; Ekström, Lena; Rane, Anders

2008-07-01

Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. The large variation in testosterone glucuronide (TG) excretion and its strong association with a deletion polymorphism in the uridine diphospho-glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio test. Our objective was to investigate whether genotype-based cutoff values will improve the sensitivity and specificity of the test. This was an open three-armed comparative study. A total of 55 healthy male volunteers with either two, one, or no allele [insertion/insertion, insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was included in the study. A single im dose of 500 mg testosterone enanthate was administered. Urinary excretion of TG after dose and the T/E ratio during 15 d were calculated. The degree and rate of increase in the TG excretion rate were highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the insertion/insertion group compared with the del/del group. Of the del/del subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the dose. When differentiated cutoff levels for the del/del (1.0) and the other genotypes (6.0) were applied, the sensitivity increased substantially for the del/del group, and false positives in the other genotypes were eliminated. Consideration of the genetic variation in disposition of androgens will improve the sensitivity and specificity of the testosterone doping test. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society.

Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.

PubMed

Montgomery, M D; Bylund, D B

2010-02-01

The alpha(2C)-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells. Human alpha(2C) wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following agonist treatment. Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325. The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.

Mirror Coronograph for Argentina (MICA). Primera Luz

NASA Astrophysics Data System (ADS)

Stenborg, G.; Epple, A.; Schwenn, R.; Francile, C.; Rovira, M.

En Julio de 1997 se terminó con la primera parte de la instalación del ``Coronógrafo de Espejo para la Argentina'' en la estación de altura Carlos U. Cesco (El Leoncito), gracias al esfuerzo de la gente del Max Planck Institut für Aeronomie (Alemania), del OAFA y del IAFE. Dicho coronógrafo forma parte de un programa de ciencia bilateral entre Alemania y Argentina. El propósito del mismo, en conjunción con otros telescopios solares y terrestres, es contribuir a un mejor entendimiento de cuestiones fundamentales de la física solar. Para ello, ya está observando la corona de emisión en el verde (Fe XIV), rojo (Fe X) y Hα entre 1.05 y 2 radios solares aproximadamente. El diseño del instrumento, el cual fuera ya presentado en esta misma reunión en La Plata en 1996, es esencialmente similar al del telescopio LASCO-C1 a bordo del Solar Heliospheric Observatory (SOHO). La adquisición de datos se realiza con un CCD de 1280x1024 pixels, codificando en 12 bits, pudiendo ser el mismo operado en forma remota. En esta reunión presentaremos algunas de las observaciones realizadas durante la puesta a punto del instrumento en el período julio-setiembre de 1997. Asimismo expondremos cómo y por qué sus resultados complementarán a los de su par en el espacio.

Espectroscopia del Cometa Halley

NASA Astrophysics Data System (ADS)

Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

1987-05-01

Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

[Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

CHEK2 1100delC and male breast cancer in the Netherlands.

PubMed

Wasielewski, Marijke; den Bakker, Michael A; van den Ouweland, Ans; Meijer-van Gelder, Marion E; Portengen, Henk; Klijn, Jan G M; Meijers-Heijboer, Hanne; Foekens, John A; Schutte, Mieke

2009-07-01

Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2-14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.

Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic)

PubMed Central

Posukh, Olga L.; Teryutin, Fedor M.; Solovyev, Aisen V.; Klarov, Leonid A.; Romanov, Georgii P.; Gotovtsev, Nyurgun N.; Kozhevnikov, Andrey A.; Kirillina, Elena V.; Sidorova, Oksana G.; Vasilyevа, Lena M.; Fedotova, Elvira E.; Morozov, Igor V.; Bondar, Alexander A.; Solovyevа, Natalya A.; Kononova, Sardana K.; Rafailov, Adyum M.; Sazonov, Nikolay N.; Alekseev, Anatoliy N.; Tomsky, Mikhail I.; Dzhemileva, Lilya U.; Khusnutdinova, Elza K.; Fedorova, Sardana A.

2016-01-01

Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic region in Russia. The complete sequencing of the non-coding and coding regions of the GJB2 gene was performed in 393 patients with HI (Yakuts—296, Russians—51, mixed and other ethnicities—46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n = 80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2 gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous state) were found in 192 out of 393 patients (48.85%). We found that the most frequent GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to be the most frequent among the Russian patients. The carrier frequencies of the c.-23+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and 2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical (2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic variants in HI in the population of the Sakha Republic (48.85%) was the highest among all of the previously studied regions of Asia. We suggest that extensive accumulation of the c.-23+1G>A pathogenic variant in the indigenous Yakut population (92.20% of all mutant chromosomes in patients) and an extremely high (10.20%) carrier frequency in the control group may indicate a possible selective advantage for the c.-23+1G>A carriers living in subarctic climate. PMID:27224056

International Celestial Reference Frame (ICRF): mantenimiento y extensión

NASA Astrophysics Data System (ADS)

Ma, C.; Arias, E. F.; Eubanks, T.; Fey, A. L.; Gontier, A.-M.; Jacobs, C. S.; Sovers, O. J.; Archinal, B. A.; Charlot, P.

A partir de enero de 1998 el sistema de referencia celeste convencional está representado por el International Celestial Reference System (ICRS) y materializado a través de las coordenadas VLBI del conjunto de radiofuentes extragalácticas que conforman el International Celestial Reference Frame (ICRF). La primera realización del ICRF, fue elaborada en 1995 por un grupo de expertos designado por la IAU, la que encomendó al International Earth Rotation Service el mantenimiento del ICRS, del ICRF y del vínculo con marcos de referencia en otras frecuencias. Una primera extensión del ICRF se realizó entre abril y junio de 1999, con el objetivo primario de proveer posiciones de radiofuentes extragalácticas observadas a partir de julio de 1995 y de mejorar las posiciones de las fuentes ``candidatas" con la inclusión de observaciones adicionales. Objetivos secundarios fueron monitorear a las radiofuentes para verificar que siguen siendo adecuadas para realizar al ICRF y mejorar las técnicas de análisis de datos. Como resultado del nuevo análisis se obtuvo una solución a partir de la cual se construyó la primera extensión del ICRF, denominada ICRF - Ext.1. Ella representa al ICRS, sus fuentes de definición se mantienen con las mismas posiciones y errores que en la primera realización del ICRF; las demás radiofuentes tienen coordenadas mejor determinadas que en ICRF; el marco de referencia se densificó con el agregado de 59 nuevas radiofuentes.

Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

PubMed Central

Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

2010-01-01

OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

Forensic applicability of multi-allelic InDels with mononucleotide homopolymer structures.

PubMed

Zhang, Shu; Zhu, Qiang; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Yang, Yiwen; Gao, Zehua; Fang, Ting; Wang, Yufang; Zhang, Ji

2018-04-27

Insertion/deletion polymorphisms (InDels), which possess the characteristics of low mutation rates and a short amplicon size, have been regarded as promising markers for forensic DNA analysis. InDels can be classified as bi-allelic or multi-allelic, depending on the number of alleles. Many studies have explored the use of bi-allelic InDels in forensic applications, such as individual identification and ancestry inference. However, multi-allelic InDels have received relatively little attention. In this study, InDels with 2-6 alleles and a minor allele frequency ≥0.01, in Chinese Southern Han (CHS), were retrieved from the 1000 Genomes Project Phase III. Based on the structural analysis of all retrieved InDels, 17 multi-allelic markers with mononucleotide homopolymer structures were selected and combined in one multiplex PCR reaction system. Sensitivity, species specificity and applicability in forensic case work of the multiplex were analyzed. A total of 218 unrelated individuals from a Chinese Han population were genotyped. The combined discriminatory power (CDP), the combined match probability (CMP) and the cumulative probability of exclusion (CPE) were 0.9999999999609, 3.91E-13 and 0.9956, respectively. The results demonstrated that this InDel multiplex panel was highly informative in the investigated population and most of the 26 populations of the 1000 Genomes Project. The data also suggested that multi-allelic InDel markers with monomeric base pair expansions are useful for forensic applications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Microwave Observations and Modeling of O2 (1-delta(sub g)) and O3 Diurnal Variation in the Mesosphere

NASA Technical Reports Server (NTRS)

Sandor, Brad J.; Clancy, R. Todd; Rusch, David W.; Randall, Cora E.; Eckman, Richard S.; Siskind, David S.; Muhleman, Duane O.

1997-01-01

The first microwave measurements of an electronically excited molecular species in the Earth's atmosphere are presented. Local thermodynamic equilibrium (LTE) rotational line emission from mesospheric O2(1-del(sub g)) was observed at a frequency of 255.01794 GHz (lambda is approx. 1.2 mm), employing the National Radio Astronomy Observatory (NRAO) millimeter facility at Kitt Peak, Arizona (32 N, 111 W). The pressure broadened line shapes of the O2(1-del(sub g)) spectra, which were obtained in January and April 1992 and in January and November 1993, are inverted to retrieve O2(1-del(sub g)) mixing profiles over the 50-70 km altitude region. The observed daytime abundances exceed ozone abundances in the lower mesosphere, which are separately retrieved with coincident O3 spectral line (249.7886 GHz) observations. The January and November 1993 observations are binned into 20-60 min time intervals to study O2(1-del(sub g)) diurnal behavior. Derived abundances of O2(1-del(sub g)) between 50 and 70 km for the four observation dates are 9%, 31%, 3%, and 26%, respectively, each +/- 10% higher than predicted, based on the simple photochemistry of lower mesospheric O2(1-del(sub g)). Modeled variation of [O2(1-del(sub g))] with time of day agrees with observed variation in that the observed difference between model and data abundances is constant throughout the daylight hours of each observation date. Model underprediction Of [02(lAg)] is consistent with similar model underprediction of mesospheric [O3]. A perturbation to the photochemical model that forces decreased ozone chemical loss brings brings both model [O3] and [O2(1-del(sub g))] into agreement with the observations. O2(1-del(sub g)) abundances derived from these 1.2 mm observations agree with [O2(1-del(sub g))] values derived from comparable SME observations of the 1.27 micrometers emission, with assumption of a 3880 sec O2(1-del(sub g)) radiative lifetime. The 6800 sec O2(1-del(sub g)) radiative lifetime proposed by Mlynczak and Nesbitt is ruled out by the similar comparison.

Tierra del Fuego, Argentina, South America

NASA Technical Reports Server (NTRS)

1991-01-01

The Mitre Peninsula is the easternmost tip of Tierra del Fuego, Argentina, (54.5S, 65.5W). Early winter snow can be seen on this south tip of the Andes Mountains. These same mountains continue underwater to Antarctica. The Strait of Magellan, separating the South American mainland from Tierra del Fuego is off the scene to the north and west, but the Strait of LeMaire, separating Tierra del Fuego from the Isla de los Estados can be seen.

Desgarros del epitelio pigmentario de la retina: factores de riesgo, mecanismo y control terapéutico.

PubMed

Clemens, Christoph R; Eter, Nicole

2017-07-11

Los desgarros del epitelio pigmentario de la retina (EPR) se asocian en la mayoría de los casos con los desprendimientos vascularizados del EPR debido a una degeneración macular asociada a la edad (DMAE), y normalmente implican una pérdida adversa de la agudeza visual. Estudios recientes indican que ha habido un aumento en la incidencia de desgarros del EPR desde la introducción de fármacos anti-factor de crecimiento del endotelio vascular (anti-VEGF) así como una asociación temporal entre el desgarro y la inyección intravítrea. Dado que el número de pacientes con DMAE y el número de inyecciones anti-VEGF va en aumento, tanto la dificultad de prevenir desgarros del EPR como el tratamiento tras la formación de los desgarros han adquirido una mayor relevancia. De forma paralela, la evolución de la imagenología de la retina ha contribuido de manera significativa a comprender mejor el desarrollo de los desgarros del EPR en los últimos años. Esta revisión resume los conocimientos que se poseen actualmente sobre el desarrollo, los factores pronósticos y las estrategias terapéuticas de los desgarros del EPR antes y después de que estos se formen. © 2017 S. Karger AG, Basel.

Índice UV

EPA Pesticide Factsheets

Información general sobre el Índice UV que proporciona un pronóstico del riesgo esperado de sobreexposición a la radiación ultravioleta (UV) del sol. El índice UV va acompañado de recomendaciones para protegerse del sol.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

PubMed

Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation

PubMed Central

Herrera, Alex F.; Mei, Matthew; Low, Lawrence; Kim, Haesook T.; Griffin, Gabriel K.; Song, Joo Y.; Merryman, Reid W.; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R.; Budde, Lihua E.; Chan, Wing C.; Chen, Robert; Davids, Matthew S.; Freedman, Arnold S.; Fisher, David C.; Jacobsen, Eric D.; Jacobson, Caron A.; LaCasce, Ann S.; Murata-Collins, Joyce; Nademanee, Auayporn P.; Palmer, Joycelynne M.; Pihan, German A.; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R.; Zain, Jasmine; Rosen, Steven T.; Kwak, Larry W.; Weinstock, David M.; Forman, Stephen J.; Weisenburger, Dennis D.; Kim, Young; Rodig, Scott J.; Krishnan, Amrita

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P = .013), and 4-year OS was 25% versus 61% (P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT. PMID:28034071

Naturally occurring deletions/insertions in HBV core promoter tend to decrease in hepatitis B e antigen-positive chronic hepatitis B patients during antiviral therapy.

PubMed

Peng, Yaqin; Liu, Baoming; Hou, Jinlin; Sun, Jian; Hao, Ran; Xiang, Kuanhui; Yan, Ling; Zhang, Jiangbo; Zhuang, Hui; Li, Tong

2015-01-01

Mutations in HBV core promoter (CP) are suggested to affect viral replication and disease progression. We investigated CP deletion/insertion mutations (Del/Ins) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients before and during antiviral treatment. Direct and clone sequencings were used for detection of CP Del/Ins in 12 patients. The dynamic changes of CP Del/Ins were tracked in these cases until week 48 of treatment. The effects of Del/Ins on CP activities and hepatitis B X protein (HBx) were analysed using luciferase assay and sequence comparison, respectively. Furthermore, 292 untreated HBeAg-positive CHB cases were also analysed. Twelve cases with multi-peak PCR direct sequencing electropherograms at baseline were confirmed to have CP Del/Ins by clone sequencing, with detection rates varying from 14.8% to 93.3% of clones analysed. Follow-up studies showed the detection rates of CP Del/Ins in patients decreased from 100% (12/12) at baseline to 16.7% (2/12) at week 48 of treatment (P<0.001), in parallel with a decline in HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase (ALT) and aspartate transaminase (AST) levels along with an increase in HBeAg loss. Luciferase assay results showed distinct promoter activities among Del/Ins-harbouring CP sequences. Importantly, 71.8% (148/206) of Del/Ins sequences potentially resulted in HBx carboxy-terminal truncations. CP Del/Ins mutations were also found in 27.4% (80/292) of untreated cases. Naturally occurring complex of CP Del/Ins mutants existed in untreated HBeAg-positive CHB patients. These mutations would affect HBV transcription activities and integrity of HBx, which might correlate with disease progression. Their prevalence decreases on antiviral therapy in parallel with the decline in HBV DNA, HBsAg and ALT and AST levels.

CDC25AQ110del: A Novel Cell Division Cycle 25A Isoform Aberrantly Expressed in Non-Small Cell Lung Cancer

PubMed Central

Younis, Rania H.; Cao, Wei; Lin, Ruxian; Xia, Ronghui; Liu, Zhenqiu; Edelman, Martin J.; Mei, Yuping; Mao, Li; Ren, Hening

2012-01-01

Objective Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25AQ110del, on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients. Methodology/Principal Findings Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25AQ110del in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25AQ110del expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25AQ110del were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25Awt, CDC25AQ110del protein had longer half-life; cells expressing CDC25AQ110del were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25AQ110del expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25AQ110del relative to the adjacent lung tissues to have significantly inferior overall survival (P = .0018). Significance Here we identified CDC25AQ110del as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies. PMID:23071577

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

Fang, Xu-Qian; Liu, Xiang-Fan; Yao, Ling

Highlights: •A novel FAK splicing mutation identified in breast tumor. •FAK-Del33 mutation promotes cell migration and invasion. •FAK-Del33 mutation regulates FAK/Src signal pathway. -- Abstract: Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introducedmore » into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.« less

Factors associated with poor sleep quality in women with cancer.

PubMed

Mansano-Schlosser, Thalyta Cristina; Ceolim, Maria Filomena

2017-03-02

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

Cambios históricos en el aporte terrígeno de la cuenca del Río de la Plata sobre la plataforma interna Uruguaya

NASA Astrophysics Data System (ADS)

Marrero, Analía; Tudurí, Adriana; Pérez, Laura; Cuña, Caroline; Muniz, Pablo; Lopes Figueira, Rubens; Michaelovitch de Mahiques, Michel; Alves de Lima Ferreira, Paulo; Pittauerová, Daniela; Hanebuth, Till; García Rodríguez, Felipe

2014-12-01

El Río de la Plata (RdlP) presenta significativas variaciones naturales (hidrodinámicas y oceanográficas) asociadas a diferentes condiciones climáticas. El propósito de este trabajo es inferir los cambios de aportes continentales de sedimentos y su relación con las variaciones hidrológicas del Río de la Plata, a través del análisis de proxies sedimentológicos y geoquímicos en testigos de sedimentos de la plataforma interna uruguaya que registran los últimos 100 años, aproximadamente. A partir de la datación por 210Pb de dos testigos de sedimentos (GeoB 13813-4 y BAR1) se reconstruyó la geocronología del ambiente, y se relacionó con datos de las forzantes climáticas Pacific Decadal Oscillation, El Niño/La Niña Southern Oscillation, Atlantic Multidecadal Oscillation, y las anomalías hidrológicas de los ríos Paraná y Uruguay. Los valores más positivos y estables del Southern Oscillation Index, los cuales corresponden a fases La Niña, se observan en el periodo correspondiente entre 1910-1970, respecto al resto de la serie, donde se aprecia una mayor variabilidad y una tendencia hacia valores más negativos (eventos El Niño). Se hicieron dendrogramas (clustering) jerárquicos para ambos testigos. Para el testigo GeoB 13813-4, se utilizó la relación Ca/Ti y la granulometría, mientras que para BAR1 se recurrió a variables granulométricas y la tasa de sedimentación. El mayor aporte continental hacia la región de la plataforma adyacente al Río de la Plata registrado a partir del año 1970, podría ser el factor principal de los agrupamientos observados en los clusters para ambos testigos. Las agrupaciones mostraron una diferenciación en la década de 1970, lo que estaría asociado al aumento de los caudales de los ríos Paraná y Uruguay, durante las últimas tres décadas del siglo XX. Por otra parte se observa que la granulometría del testigo BAR1 presentó un mayor tamaño de grano y más variabilidad que en el caso del testigo GeoB 13813-4. También se determinó una mayor acumulación de sedimentos a través del tiempo en el cinturón de barro del Río de la Plata (plataforma continental adyacente), comparado con aquel registrado en la Barra del Indio (límite entre zona intermedia y externa del estuario). Estas diferencias podrían estar relacionadas con la influencia del Río de la Plata, el cual genera un ambiente altamente dinámico sobre la Barra del Indio y un ambiente más estable sobre el cinturón de barro en la plataforma continental.

Reconversion Militar del Ejercito en la Frontera Dominico-Haitiana (Military Restructuring of the Army on the Dominican-Haitian Border)

DTIC Science & Technology

2013-05-22

Estado Mayor del Ejército de EE. UU. en cumplimiento parcial de los requisitos para la obtención del grado de MAESTRÍA EN CIENCIAS Y ARTES...MILITARES Estudios Generales Por MAYOR FELIPE CÉSPEDES TEJERA, EJÉRCITO NACIONAL DOMINICANO Licenciado en Ciencias Sociales, Universidad...ANSI Std. Z39.18 ii MAESTRÍA EN ARTES Y CIENCIAS MILITARES PÁGINA DE APROBACIÓN DE LA TESIS Nombre del Candidato: Mayor Felipe Céspedes Tejera

CHEK2*1100delC Variant and BRCA1/2-Negative Familial Breast Cancer - A Family-Based Genetic Association Study

DTIC Science & Technology

2007-10-01

AD_________________ Award Number: DAMD17-03-1-0774 TITLE: CHEK2 *1100delC Variant and BRCA1/2...NUMBER CHEK2 *1100delC Variant and BRCA1/2-Negative Familial Breast Cancer - A Family- Based Genetic Association Study 5b. GRANT NUMBER DAMD17...association between the CHEK2 *1100delC gene variant and breast cancer among BRCA1/2-negative families. Vital to DNA replication and normal growth of breast

Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome.

PubMed

Matsunoshita, Natsuki; Nozu, Kandai; Yoshikane, Masahide; Kawaguchi, Azusa; Fujita, Naoya; Morisada, Naoya; Ishimori, Shingo; Yamamura, Tomohiko; Minamikawa, Shogo; Horinouchi, Tomoko; Nakanishi, Keita; Fujimura, Junya; Ninchoji, Takeshi; Morioka, Ichiro; Nagase, Hiroaki; Taniguchi-Ikeda, Mariko; Kaito, Hiroshi; Iijima, Kazumoto

2018-05-30

Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.

Utility of whole exome sequencing in the diagnosis of Usher syndrome: Report of novel compound heterozygous MYO7A mutations.

PubMed

Ramzan, Khushnooda; Al-Owain, Mohammed; Huma, Rozeena; Al-Hazzaa, Selwa A F; Al-Ageel, Sarah; Imtiaz, Faiqa; Al-Sayed, Moeenaldeen

2018-05-01

Next generation sequencing (NGS), such as targeted panel sequencing, whole-exome sequencing and whole-genome sequencing has led to an exponential increase of elucidated genetic causes in both rare diseases, and common but heterogeneous disorders. NGS is applied in both research and clinical settings, and the clinical exome sequencing (CES), which provides not only the sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to a genetic diagnosis. Usher syndrome is a group of disorders, characterized by bilateral sensorineural hearing loss, with or without vestibular dysfunction and retinitis pigmentosa. The index patient, a 2-year-old child was initially diagnosed with nonsyndromic hearing impairment. Homozygosity mapping followed by CES was utilized as a diagnostic tool to identify the genetic basis of his hearing loss. A paternally inherited novel insertion, c.198_199insA (p.Val67Serfs*73) and a maternally inherited novel deletion, c.1219_1226del (p.Phe407Aspfs*33) in gene MYO7A were found in compound heterozygous state in the index patient. The result expands the mutational spectrum of MYO7A. In addition it helped in early diagnosis of the syndrome, for planning and adjustments for the patient, and as well as for future family planning. This study highlights the clinical effectiveness of CES for Usher syndrome diagnosis in a child presented with congenital hearing loss. Copyright © 2018. Published by Elsevier B.V.

Parasite infracommunities of a specialized marine fish species in a compound community dominated by generalist parasites.

PubMed

Lanfranchi, A L; Rossin, M A; Timi, J T

2009-12-01

The structure and composition of parasite communities of Mullus argentinae were analysed under two alternative hypotheses in a sample of 75 specimens caught off Mar del Plata, Argentina (38 degrees 27'S, 57 degrees 90'W). The first, based on the dominance of trophically transmitted larval parasites of low host-specificity among fish species in the region, predicts that infracommunities will be random subsets of regionally available species. The second, based on previous studies on other mullids, predicts that infracommunities will be dominated by adult digeneans. The parasite fauna of goatfishes was mainly composed of endoparasites, with metacercariae of Prosorhynchus australis accounting for most individual parasites and greatly affecting infracommunity descriptors. Its importance was reinforced by the low number of trophically transmitted larval parasites. Both hypotheses were refuted; parasite communities were not dominated either by trophically transmitted larval parasites of low host-specificity or by adult digeneans. Prosorhynchus australis was the only species displaying any degree of phylogenetic specificity. Therefore, the influence of phylogenetic factors seems to exceed that of ecological ones in determining the observed structure of infracommunities. However, it is precisely host ecology that allows P. australis to become the determinant of infracommunity structure by constraining the acquisition of other parasites. Studies aiming to determine the relative importance of evolutionary and ecological processes as structuring forces of parasite communities should take into account not only the identity and specificity of their component parasites, but also their availability in the compound community.

Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions

PubMed Central

Bliznetz, Elena A; Lalayants, Maria R; Markova, Tatiana G; Balanovsky, Oleg P; Balanovska, Elena V; Skhalyakho, Roza A; Pocheshkhova, Elvira A; Nikitina, Natalya V; Voronin, Sergey V; Kudryashova, Elena K; Glotov, Oleg S; Polyakov, Alexander V

2017-01-01

Although mutations in the GJB2 gene sequence make up the majority of variants causing autosomal-recessive non-syndromic hearing loss, few large deletions have been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1 hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report frequency in Russia, clinical significance and evolutionary origins of a 101 kb deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of 1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus, the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and this allele was shown to be predominantly associated with profound sensorineural hearing loss. Additionally, eight previously unpublished GJB2 mutations were described in this study. All patients carrying del(GJB2-D13S175) were of the Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of haplotypes associated with the deletion revealed a common founder in the Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175) was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has been added to our routine testing strategy for DFNB1 hearing loss. PMID:28405014

Effect of the F508del genotype on outcomes of endoscopic sinus surgery in children with cystic fibrosis.

PubMed

Do, Bao Anh Julie; Lands, Larry C; Saint-Martin, Christine; Mascarella, Marco A; Manoukian, John J; Daniel, Sam J; Nguyen, Lily H P

2014-07-01

Numerous authors have sought to describe genotype-phenotype correlations in cystic fibrosis (CF), notably to pancreatic insufficiency and lung disease. However, few studies have focused on the association between the F508del genotype and response to sinus surgery. The objective of this study is to assess the effect of the F508del genotype on sinonasal disease severity and outcomes following functional endoscopic sinus surgery (FESS) in a pediatric population. A retrospective chart review of 153 children with CF seen at a tertiary care pediatric hospital from 1995 to 2008 was performed. Patients were classified into one of three groups according to F508del genotype, either as homozygous, heterozygous or not carrying a F508del mutation. The sinonasal disease phenotype of the three groups was compared based on clinical and radiological findings, extent of endoscopic sinus surgery and rate of revision surgery. The relationship between the F508del genotype and pancreatic insufficiency was confirmed (p<0.05). There was no association between the F508del genotype and increased need for FESS (p=0.75). Moreover, no association was established between F508del homozygosity and presence of nasal polyps, Lund-Mackay score, extent of surgery or length of postoperative hospitalization. The rates of revision surgery did not differ significantly among the three genotypes analyzed (p=0.59). There is no clear association between the F508del genotype and an increased need for FESS, extent of surgery, or revision surgery. Given the phenotypic variability of sinonasal disease in patients with CF, a prospective study is needed to better understand outcomes following FESS and the contribution of gene modifiers to this effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.

PubMed

Cosson, Adrien; Chapiro, Elise; Belhouachi, Nabila; Cung, Hong-Anh; Keren, Boris; Damm, Frederik; Algrin, Caroline; Lefebvre, Christine; Fert-Ferrer, Sandra; Luquet, Isabelle; Gachard, Nathalie; Mugneret, Francine; Terre, Christine; Collonge-Rame, Marie-Agnes; Michaux, Lucienne; Rafdord-Weiss, Isabelle; Talmant, Pascaline; Veronese, Lauren; Nadal, Nathalie; Struski, Stephanie; Barin, Carole; Helias, Catherine; Lafage, Marina; Lippert, Eric; Auger, Nathalie; Eclache, Virginie; Roos-Weil, Damien; Leblond, Veronique; Settegrana, Catherine; Maloum, Karim; Davi, Frederic; Merle-Beral, Helene; Lesty, Claude; Nguyen-Khac, Florence

2014-08-01

Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS. © 2014 Wiley Periodicals, Inc.

Población de galaxias de baja luminosidad en cúmulos

NASA Astrophysics Data System (ADS)

Valotto, C. A.; Muriel, H.; Moore, B.; García Lambas, D.

En este trabajo se discute sobre la presencia de un exceso de galaxias de baja luminosidad en medios de alta densidad de galaxias y la posibilidad de que los halos de galaxias cD puedan ser formados a partir de galaxias en cúmulos ricos, los cuales muestran una función de luminosidad (FL) con el extremo débil plano. Se analizaron muestras de cúmulos cercanos obtenidas a partir de los catálogos de Abell y X-ray Sample of Bright Clusters. Los resultados obtenidos muestran que los cúmulos de galaxias que tienen emisión en rayos X detectada poseen una FL plana (α ≈ -1.2), consistente con los valores encontrados para las galaxias de campo. En cambio, los cúmulos de galaxias identificados a partir de distribuciones bidimensionales de galaxias que no tienen su contraparte en rayos X, muestran una FL con una pendiente pronunciada en el extremo débil (α ≈ -1.6). Se examinaron además, los posibles efectos debido a la presencia de una galaxia central dominante sobre el extremo débil de la FL. Se analizaron muestras de acuerdo a la clasificación Bautz-Morgan dividiendo en las submuestras I,I-II y II, II- III, III. Las FL resultantes para ambas muestras son indistinguibles. Nuestros resultados son consistentes con la hipótesis de que los efectos de proyección en cúmulos identificados en dos dimensiones pueden producir un exceso artificial de galaxias de baja luminosidad.

Improving mating performance of mass-reared sterile Mediterranean fruit flies (Diptera: Tephritidae) through changes in adult holding conditions: demography and mating competitiveness

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

Liedo, P.; Salgado, S.; Oropeza, A.

Mass rearing conditions affect the mating behavior of Mediterranean fruit flies (medflies) Ceratitis capitata (Wiedemann). We evaluated the effect of slight changes in the adult holding conditions of adult flies maintained for egg production on their mating performance. Colonization was initiated from wild flies collected as larvae from infested coffee berries (Coffea arabica L.). When pupae were close to adult emergence, they were randomly divided into 3 groups and the emerging adults were reared under the following conditions: (1) Metapa System (MS, control), consisting of 70 x 45 x 15 cm aluminum frame, mesh covered cages, with a density ofmore » 2,200 flies per cage and a 1:1 initial sex ratio; (2) Insert System (IS), with the same type of cage, and the same fly density and sex ratio as in the MS treatment, but containing twelve Plexiglas pieces (23 x 8.5 cm) to provide additional horizontal surface areas inside the cage; and (3) Sex-ratio System (SS), same as IS, but in this case the initial male: female ratio was 4:1. Three d later, newly emerged females were introduced, so the ratio became 3:1 and on the 6th d another group of newly emerged females was added to provide a 2:1 final sex ratio, at which the final density reached 1,675 flies per cage. The eggs collected from each of the 3 treatments were reared independently following standard procedures and the adults were held under the same experimental conditions. This process was repeated for over 10 to 13 generations (1 year). The experiment was repeated 3 times in 3 consecutive years, starting each replicate with a new collection of wild flies. Life tables were constructed for each treatment at the parental, 3rd, 6th, and 9th generations. Standard quality control parameters (pupation at 24 h, pupal weight, adult emergence, and flight ability), were estimated for each treatment every third generation in the third year. For the last generation each year, mating competitiveness was evaluated in field cage tests with wild flies. As colonization progressed, life expectancy and fecundity rates increased in the 3 rearing systems. There was no significant difference in standard quality control parameters among the 3 rearing systems. Wild males always achieved more matings than any of the mass reared males. Mating competitiveness of males from the IS, although surprisingly not from the SS, was significantly greater than that of males from the MS. Our results indicate that these slight changes in the adult holding conditions can significantly reduce the harmful effects of mass rearing on the mating performance of sterile flies. (author) [Spanish] Se ha demostrado que las condiciones de cria masiva afectan el comportamiento de apareamiento de la mosca del Mediterraneo Ceratitis capitata (Wiedemann). Nosotros evaluamos el efecto de ligeros cambios en las condiciones en las que los adultos son mantenidos para la produccion de huevos, en el desempeno de apareamiento de las moscas esteriles. La colonizacion se inicio con moscas silvestres colectadas como larvas en cerezas de cafe (Coffea arabica L.) infestadas. Cuando las pupas estuvieron cerca de la emergencia de los adultos, se dividieron en tres grupos al azar y los adultos recien emergidos fueron criados en las siguientes condiciones: (1) Sistema Metapa (MS, testigo), consistente en jaulas con marco de aluminio de 70 x 45 x 15 cm, cubiertas con malla, con una densidad de 2,200 moscas por jaula y una relacion de sexos inicial de 1:1; (2); Sistema Insertos (IS), con el mismo tipo de jaula, densidad de moscas, y relacion de sexos que en el MS, pero conteniendo 12 piezas de plexiglas (23 x 8.5 cm) para proporcionar superficie horizontal al interior de la jaula; y (3) Sistema de Relacion de Sexos (SS), igual que el IS, pero en este caso la relacion inicial macho: hembra fue de 4:1, tres dias despues se introdujeron hembras recien emergidas para tener una relacion de 3:1 y en el 6 dia se anadio otro grupo de hembras para tener una relacion final de sexos de 2:1, que equivale a una densidad final de 1,675 moscas por jaula. Los huevos colectados de cada tratamiento fueron criados independientemente siguiendo los procedimientos estandares y los adultos fueron mantenidos en las mismas condiciones experimentales. Esto se repitio por 10 a 13 generaciones (un ano). El experimento se repitio en tres ocasiones en anos consecutivos, iniciando cada repeticion con una nueva colecta de moscas silvestres. Se construyeron tablas de vida de cada tratamiento en las generaciones parental, 3 a, 6 a y 9 a . Se estimaron los parametros estandares de calidad (pupacion a las 24 h, peso de pupa, emergencia de adultos y habilidad de vuelo) para cada tratamiento, cada tercera generacion en el tercer ano. En la ultima generacion de cada ano, se evaluo la competitividad sexual en pruebas en jaulas de campo con moscas silvestres. Conforme avanzo la colonizacion, se encontro que la esperanza de vida y las tasas de fecundidad se incrementaron en los tres sistemas de cria. No hubo diferencia significativa en los parametros estandar de control de calidad entre los tres sistemas. Los machos silvestres siempre lograron mas apareamientos que los machos procedentes de cada sistema de cria masiva. La competitividad de los machos del sistema IS fue significativamente mayor que la de los machos del sistema MS. Nuestros resultados indican que estas ligeras modificaciones en las condiciones de la colonia de adultos reducen los efectos adversos de la cria masiva sobre el desempeno de apareamiento de los machos esteriles. (author)« less

A Visual Reporter System for Virus-Induced Gene Silencing in Tomato Fruit Based on Anthocyanin Accumulation1[C][W

PubMed Central

Orzaez, Diego; Medina, Aurora; Torre, Sara; Fernández-Moreno, Josefina Patricia; Rambla, José Luis; Fernández-del-Carmen, Asun; Butelli, Eugenio; Martin, Cathie; Granell, Antonio

2009-01-01

Virus-induced gene silencing (VIGS) is a powerful tool for reverse genetics in tomato (Solanum lycopersicum). However, the irregular distribution of the effects of VIGS hampers the identification and quantification of nonvisual phenotypes. To overcome this limitation, a visually traceable VIGS system was developed for fruit, comprising two elements: (1) a transgenic tomato line (Del/Ros1) expressing Antirrhinum majus Delila and Rosea1 transcription factors under the control of the fruit-specific E8 promoter, showing a purple-fruited, anthocyanin-rich phenotype; and (2) a modified tobacco rattle virus VIGS vector incorporating partial Rosea1 and Delila sequences, which was shown to restore the red-fruited phenotype upon agroinjection in Del/Ros1 plants. Dissection of silenced areas for subsequent chemometric analysis successfully identified the relevant metabolites underlying gene function for three tomato genes, phytoene desaturase, TomloxC, and SlODO1, used for proof of concept. The C-6 aldehydes derived from lipid 13-hydroperoxidation were found to be the volatile compounds most severely affected by TomloxC silencing, whereas geranial and 6-methyl-5-hepten-2-one were identified as the volatiles most severely reduced by phytoene desaturase silencing in ripening fruit. In a third example, silencing of SlODO1, a tomato homolog of the ODORANT1 gene encoding a myb transcription factor, which regulates benzenoid metabolism in petunia (Petunia hybrida) flowers, resulted in a sharp accumulation of benzaldehyde in tomato fruit. Together, these results indicate that fruit VIGS, enhanced by anthocyanin monitoring, can be a powerful tool for reverse genetics in the study of the metabolic networks operating during fruit ripening. PMID:19429602

Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome.

PubMed

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema

2017-01-01

Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.

Pesticides in water sources from the East of Santiago del Estero, Argentina

NASA Astrophysics Data System (ADS)

Inés Mas, Laura; Aparicio, Virginia; De Geronimo, Eduardo; Costa, José Luis

2017-04-01

Occurrence of pesticides in water, specially when it comes to drinking water, is a topic of great concern for local communities of agricultural areas. Therefore, the aim of this study was to monitor the presence of pesticides in water samples from different sources and to determine if the values found represent a risk for the population that consumes it. Samplings took place between April 2014 and July 2016 and were carried out in times when sprays are normally made in the crops of the areas surrounding the cities of Sachayoj and Bandera, in the province of Santiago del Estero. Samples belonged to groundwater, surface water and tanks in which the rainwater is collected. 48 compounds, between pesticides and secondary metabolites, were analyzed by ultra high resolution liquid chromatography (UHPLC) combined with an MS / MS detector. Preliminary results indicate that almost half of the active substances were absent or had a very low occurrence (<15%). Those with higher frequency but below 50% generally had a significant number of cases below the limit of quantification. Finally, the molecules of higher prevalence correspond to the most commonly used pesticides, and they are mainly herbicides. For example, atrazina was present in 100% of the samples, and glyphosate appeared in 80% of the samples, with a frequency similar to its secondary metabolite, AMPA. These three molecules were also the ones that showed the highest concentrations. In all cases the measured values are below the limits of the EPA and WHO, but when compared with the limits established by the EU, although only 7% of the data obtained for the individual molecules exceeds the limit of 0.1 μg L-1, adding all the molecules for each site and sampling date 87% exceeds the limit of 0.5 μg L-1.

Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome

PubMed Central

Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema

2017-01-01

Introduction Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Methods Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Results Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. Conclusion A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort. PMID:28288174

Broadening the phenotype of DFNB28: Mutations in TRIOBP are associated with moderate, stable hereditary hearing impairment.

PubMed

Wesdorp, Mieke; van de Kamp, Jiddeke M; Hensen, Erik F; Schraders, Margit; Oostrik, Jaap; Yntema, Helger G; Feenstra, Ilse; Admiraal, Ronald J C; Kunst, Henricus P M; Tekin, Mustafa; Kanaan, Moien; Kremer, Hannie; Pennings, Ronald J E

2017-04-01

DFNB28 is characterized by prelingual, severe to profound sensorineural hearing impairment (HI). It is associated with mutations in exon 6 and 7 of TRIOBP and has not been reported in the European population. Here, we describe two isolated cases of Dutch origin with congenital, moderate HI and compound heterozygous mutations in TRIOBP. Three of the mutations are novel, one nonsense mutation (c.5014G>T (p.Gly1672*)) and two frameshift mutations (c.2653del (p.Arg885Alafs*120) and c.3460_3461del (p.Leu1154Alafs*29)). The fourth mutation is the known c.3232dup (p.Arg1078Profs*6) mutation. Longitudinal audiometric analyses in one of the subjects revealed that HI was stable over a period of 15 years. Vestibular function was normal. Predicted effects of the mutations do not explain the relatively mild phenotype in the presented subjects, whereas location of the mutation might well contribute to the milder HI in one of the subjects. It is known that isoform classes TRIOBP-4 and TRIOBP-5 are important for stereocilia stability and rigidity. To our knowledge, p.Gly1672* is the first pathogenic variant identified in DFNB28 that does not affect isoform class TRIOBP-4. This suggests that a single TRIOBP copy to encode wildtype TRIOBP-4 is insufficient for normal hearing, and that at least one TRIOBP copy to encode TRIOBP-5 is indispensable for normal inner ear function. Furthermore, this study demonstrates that DFNB28 can be milder than reported so far and that mutations in TRIOBP are thus associated with a heterogeneous phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of air quality in Mexico City due to particles smaller than ten microns (PM10) by wildland fire in "Cumbres del Ajusco Park" for the year 2013

NASA Astrophysics Data System (ADS)

Mendoza, A.; Garcia-Reynoso, J. A.; Ruiz-Suárez, L. G.; Torres, R.; Castro, T.; Peralta, O.; Padilla Barrera, Z. V.; Mar, B.; Carbajal, J. N.

2014-12-01

A forest fire is a natural process of combustion in a specific geographical area, its occurrence depends on meteorological variables, topography and vegetation type, the wildland fires are potential sources of large amounts of pollutants. The main air pollutants are in a wildland fires particles (PM10 and PM2.5) Carbon Monoxide (CO), nitrogen oxides (NOx), volatile organic compounds (VOC's) and a negligible amount of sulfur dioxide (SO2) (Chow 1995), Was performed a study of the environmental impact on air quality in Mexico city for a wildland fire. The fire was presented in Cumbres del Ajusco Park on April 14 for the year 2013, with a duration of 26 hours and consuming an extension 150 ha of pasture, WRF-Chem and WRF-fire model were used to conduct the study, two modeling scenarios were made, one including emissions from wildfire and other without emission-fire, comparison is made between the two modeling scenarios in order to calculate on air quality in Mexico cityPM10 concentrations have a larger impact on the air quality of Mexico city, when fire emission were included, a plume of PM10 coming from fire increase ambient concentration up to 350ug/m3 and it was obtained by modeling similar to the concentration measured by a monitoring station (320ug/m3).The current limit is 120ug/m3 24 hours average. (Mexican standard NOM-025-SSA1-1993)This system for setting emissions from fire is working properly whoever further development is required.

Insights into Mutation Effect in Three Poikiloderma with Neutropenia Patients by Transcript Analysis and Disease Evolution of Reported Patients with the Same Pathogenic Variants.

PubMed

Colombo, Elisa A; Elcioglu, Nursel H; Graziano, Claudio; Farinelli, Pamela; Di Fede, Elisabetta; Neri, Iria; Facchini, Elena; Greco, Mariangela; Gervasini, Cristina; Larizza, Lidia

2018-05-16

Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients. We describe the clinical features of three unreported PN patients and characterize their USB1 pathogenic variants by transcript analysis to get insights into the effect on the overall phenotype and disease evolution. A Turkish boy is homozygous for the c.531delA deletion, a recurrent mutation in Turkey; an adult Italian male is compound heterozygous for two nonsense mutations, c.243G>A and c.541C>T, while an Italian boy is homozygous for the splicing c.683_693+1del variant. The identified mutations have already been reported in PN patients who developed hematologic or skin cancer. Aberrant mRNAs of all four mutated alleles could be identified confirming that transcripts of USB1 main isoform either carrying stop codons or mis-spliced may at least partially escape nonsense-mediated decay. Our study addresses the need of gathering insights on genotype-phenotype correlations in newly described PN patients, by transcript analysis and information on disease evolution of reported patients with the same pathogenic variants.

The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene.

PubMed

Inoue, Hirofumi; Terachi, Shin-Ichi; Uchiumi, Takeshi; Sato, Tetsuji; Urata, Michiyo; Ishimura, Masataka; Koga, Yui; Hotta, Taeko; Hara, Toshiro; Kang, Dongchon; Ohga, Shouichi

2017-07-01

Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19-52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset). © 2017 Wiley Periodicals, Inc.

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence1[OPEN

PubMed Central

Leng, Yujia; Yang, Yaolong; Ren, Deyong; Dai, Liping; Wang, Yuqiong; Chen, Long; Tu, Zhengjun; Gao, Yihong; Zhu, Li; Hu, Jiang; Gao, Zhenyu; Guo, Longbiao; Lin, Yongjun

2017-01-01

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 (del1). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes. PMID:28455404

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence.

PubMed

Leng, Yujia; Yang, Yaolong; Ren, Deyong; Huang, Lichao; Dai, Liping; Wang, Yuqiong; Chen, Long; Tu, Zhengjun; Gao, Yihong; Li, Xueyong; Zhu, Li; Hu, Jiang; Zhang, Guangheng; Gao, Zhenyu; Guo, Longbiao; Kong, Zhaosheng; Lin, Yongjun; Qian, Qian; Zeng, Dali

2017-06-01

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 ( del1 ). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes. © 2017 American Society of Plant Biologists. All Rights Reserved.

Two Variants in SLC24A5 Are Associated with “Tiger-Eye” Iris Pigmentation in Puerto Rican Paso Fino Horses

PubMed Central

Mack, Maura; Kowalski, Elizabeth; Grahn, Robert; Bras, Dineli; Penedo, Maria Cecilia T.; Bellone, Rebecca

2017-01-01

A unique eye color, called tiger-eye, segregates in the Puerto Rican Paso Fino (PRPF) horse breed and is characterized by a bright yellow, amber, or orange iris. Pedigree analysis identified a simple autosomal recessive mode of inheritance for this trait. A genome-wide association study (GWAS) with 24 individuals identified a locus on ECA 1 reaching genome-wide significance (Pcorrected = 1.32 × 10−5). This ECA1 locus harbors the candidate gene, Solute Carrier Family 24 (Sodium/Potassium/Calcium Exchanger), Member 5 (SLC24A5), with known roles in pigmentation in humans, mice, and zebrafish. Humans with compound heterozygous mutations in SLC24A5 have oculocutaneous albinism (OCA) type 6 (OCA6), which is characterized by dilute skin, hair, and eye pigmentation, as well as ocular anomalies. Twenty tiger-eye horses were homozygous for a nonsynonymous mutation in exon 2 (p.Phe91Tyr) of SLC24A5 (called here Tiger-eye 1), which is predicted to be deleterious to protein function. Additionally, eight of the remaining 12 tiger-eye horses heterozygous for the p.Phe91Tyr variant were also heterozygous for a 628 bp deletion encompassing all of exon 7 of SLC24A5 (c.875-340_1081+82del), which we will call here the Tiger-eye 2 allele. None of the 122 brown-eyed horses were homozygous for either tiger-eye-associated allele or were compound heterozygotes. Further, neither variant was detected in 196 horses from four related breeds not known to have the tiger-eye phenotype. Here, we propose that two mutations in SLC24A5 affect iris pigmentation in tiger-eye PRPF horses. Further, unlike OCA6 in humans, the Tiger-eye 1 mutation in its homozygous state or as a compound heterozygote (Tiger-eye 1/Tiger-eye 2) does not appear to cause ocular anomalies or a change in coat color in the PRPF horse. PMID:28655738

Expendable Bathythermograph (XBT) Measurements in the Western Alboran Sea, October 1982

DTIC Science & Technology

1983-08-01

aircraft, shore- based radar, and shore- based meteorological stations cooperated in an intense measurement effort. As one part of this effort USNS BARTLETT...de Castillejo (1972). Contribucion a1 Conocimiento del mar de Alboran: III. Variaciones del Remolino Anticiclonico. Boletin del Institute Espanol

Clays and Clay Minerals and their environmental application in Food Technology

NASA Astrophysics Data System (ADS)

del Hoyo Martínez, Carmen; Cuéllar Antequera, Jorge; Sánchez Escribano, Vicente; Solange Lozano García, Marina; Cutillas Díez, Raul

2013-04-01

The clay materials have led to numerous applications in the field of public health (del Hoyo, 2007; Volzone, 2007) having been demonstrated its effectiveness as adsorbents of all contaminants. Some biodegradable materials are used for for adsorption of chemical contaminants: lignins (Valderrabano et al., 2008) and also clays and clay minerals, whose colloidal properties, ease of generating structural changes, abundance in nature, and low cost make them very suitable for this kind of applications. Among the strategies used at present to preserve the quality of the water and this way to diminish the environmental risk that supposes the chemical pollution, stands out the use of adsorbents of under cost, already they are natural or modified, to immobilize these compounds and to avoid the pollution of the water with the consequent reduction of environmental and economic costs Thanks to the development of the science and the technology of the nourishment in the last 50 years, there have revealed itself several new substances that can fulfill beneficial functions in the food, and these substances, named food additives, are today within reach of all. The food additives recover a very important role in the complex nourishing supply. The additives fulfill several useful functions in the food, which often we give for sat. Nevertheless the widespread use of food additives in the food production also influences the public health. The food industries, which are very important for the economy, spill residues proved from its activity that they have to be controlled to evaluate the environmental impact and to offer the necessary information about the quantitative evaluation of the chemical risk of the use of food additives for the public health. We have studied the adsorption of several contaminants by natural or modified clays, searching their interaction mechanisms and the possible recycling of these materials for environmental purposes and prevention of the health. References -del Hoyo, C. (2007). Applied Clay Science. 36, 103-121.Layered Double Hydroxides and human health: An overview. -Valderrábano, M., Rodríguez-Cruz, S., del Hoyo, C., Sánchez-Martín, M.J. (2006). 4th International Workshop "Bioavalailability of pollutants and soil remediation". 1, 5-6. Physicochemical study of the adsorption of pesticides by lignins. -Volzone, C. (2007). Applied Clay Science. 36, 191-196. Retention of pollutant gases: Comparison between clay minerals and their modified products.

Primer registro para Peru del genero Nielsonia Young, 1977 (Hemiptera: Cicadellidae: Cicadellinae: Cicadellini)

USDA-ARS?s Scientific Manuscript database

En este articulo se reporta por primera vez para el Peru una especies del genero Nielsonia Young, 1977, de material procedente del Departamento de Tumbes. El genero ha sido reportada anteriormente de Ecuador, como unico registro para Sudamerica, y America Central. El unico especimen hembra encontra...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Indian River Bay, Del. 110.65 Section 110.65 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing...

Pastoral del Nino: Bringing the Abundant Life to Paraguayan Children

ERIC Educational Resources Information Center

Austin, Ann Berghout; Aquino, Cyle; Burro, Elizabeth

2007-01-01

Pastoral del Nino is transforming children's lives in rural Paraguay. Part of Pastoral Social (Catholic Social Services), Pastoral del Nino's primary focus is to bring "vida en abundancia" (the abundant life) to families by ensuring that mothers survive childbirth and children reach their first birthdays. In addition, the organization…

Calidad del aire interior en las escuelas

EPA Pesticide Factsheets

EPA ha desarrollado el Programa de Herramientas de Calidad del Aire Interior para las Escuelas para reducir la exposición a los contaminantes ambientales en las mismas a través de la adopción voluntaria de las prácticas para manejar la calidad del aire int

The Armed Forces and the Fight against Drug-Trafficking in Honduras (Las FUERZAS ARMADAS EN EL COMBATE AL NARCOTR FICO EN HONDURAS)

DTIC Science & Technology

2013-06-13

Estado Mayor del Ejército de EE. UU. En cumplimiento parcial de los requisitos para la obtención del grado de MAESTRÍA EN CIENCIAS Y ARTES MILITARES...Estudios Generales Por WALTER D. HERNANDEZ CARVAJAL, MAYOR DEL EJÉRCITO DE HONDURAS Licenciado en Ciencias Militares...Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 ii MAESTRÍA EN ARTES Y CIENCIAS MILITARES PÁGINA DE APROBACIÓN DE LA TESIS Nombre del

Resultados del relevamiento de HI en el Cielo Austral: 3. Relevamiento de Nubes de Alta Velocidad

NASA Astrophysics Data System (ADS)

Morras, R.; Bajaja, E.; Arnal, E. M.; Pöppel, W. G. L.

Los resultados del relevamiento de HI del Hemisferio Austral fueron reprocesados con el fin de incrementar su sensibilidad. Así, se utilizó esta nueva base de datos con el fin de obtener un nuevo relevamiento de Nubes de Alta Velocidad en el cielo austral. El ruido r.m.s. alcanzado es de 0.015-0.020 K, con una resolución espectral de 8 km/seg. El cubrimiento espacial del relevamiento mejora en un factor 16 al realizado por Bajaja et al (1985).

Multi-InDel Analysis for Ancestry Inference of Sub-Populations in China

PubMed Central

Sun, Kuan; Ye, Yi; Luo, Tao; Hou, Yiping

2016-01-01

Ancestry inference is of great interest in diverse areas of scientific researches, including the forensic biology, medical genetics and anthropology. Various methods have been published for distinguishing populations. However, few reports refer to sub-populations (like ethnic groups) within Asian populations for the limitation of markers. Several InDel loci located very tightly in physical positions were treated as one marker by us, which is multi-InDel. The multi-InDel shows potential as Ancestry Inference Marker (AIM). In this study, we performed a genome-wide scan for multi-InDels as AIM. After examining the FST distributions in the 1000 Genomes Database, 12 candidates were selected and validated for eastern Asian populations. A multiplexed assay was developed as a panel to genotype 12 multi-InDel markers simultaneously. Ancestry component analysis with STRUCTURE and principal component analysis (PCA) were employed to estimate its capability for ancestry inference. Furthermore, ancestry assignments of trial individuals were conducted. It proved to be very effective when 210 samples from Han and Tibetan individuals in China were tested. The panel consisting of multi-InDel markers exhibited considerable potency in ancestry inference, and was suggested to be applied in forensic practices and genetic population studies. PMID:28004788

Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells

NASA Technical Reports Server (NTRS)

Wakahara, M.; Neff, A. W.; Malacinski, G. M.

1984-01-01

Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

Nonmutagenic carcinogens induce intrachromosomal recombination in dividing yeast cells.

PubMed

Schiestl, R H

1993-12-01

A large number of animal and human carcinogens without apparent genotoxic activity exist (nonmutagenic carcinogens) that are difficult or impossible to detect with the currently used short-term tests. Because of the association of carcinogenesis with genome rearrangement, a system selecting for intrachromosomal recombination (DEL recombination) that results in genome rearrangement has been constructed in the yeast Saccharomyces cerevisiae. Because DEL recombination is under different genetic control than interchromosomal recombination and meiotic recombination, it is probably due to a different mechanism. It has been found that DEL recombination is readily inducible by 10 mutagenic carcinogens and 17 nonmutagenic carcinogens that are not detectable (false negatives) with the Ames assay. In addition, three out of four mutagens that do not cause cancer (false positives in the Ames assay) do not induce DEL recombination. DEL recombination is inducible by UV only in dividing cells but not in cells synchronized in the G1 or G2 phase of the cell cycle. Interchromosomal recombination, on the other hand, is inducible in G1 but not in G2. The nonmutagenic carcinogens induce DEL recombination only in actively growing cells, which may give some indication as to their mechanism. Further characterization of the mechanism involved in induction of DEL recombination may contribute to the understanding of the biological activity of nonmutagenic carcinogens.

Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage.

PubMed

Li, Juan; Prins, Daniel; Park, Hyun Jung; Grinfeld, Jacob; Gonzalez-Arias, Carlos; Loughran, Stephen; Dovey, Oliver M; Klampfl, Thorsten; Bennett, Cavan; Hamilton, Tina L; Pask, Dean C; Sneade, Rachel; Williams, Matthew; Aungier, Juliet; Ghevaert, Cedric; Vassiliou, George S; Kent, David G; Green, Anthony R

2018-02-08

Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1-bp frameshift and generate a novel protein C terminus. In this study, we generated a conditional mouse knockin model of the most common CALR mutation, a 52-bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus. CALR del/+ mice develop a transplantable ET-like disease with marked thrombocytosis, which is associated with increased and morphologically abnormal megakaryocytes and increased numbers of phenotypically defined hematopoietic stem cells (HSCs). Homozygous CALR del/del mice developed extreme thrombocytosis accompanied by features of MF, including leukocytosis, reduced hematocrit, splenomegaly, and increased bone marrow reticulin. CALR del/+ HSCs were more proliferative in vitro, but neither CALR del/+ nor CALR del/del displayed a competitive transplantation advantage in primary or secondary recipient mice. These results demonstrate the consequences of heterozygous and homozygous CALR mutations and provide a powerful model for dissecting the pathogenesis of CALR-mutant ET and PMF. © 2018 by The American Society of Hematology.

Evaluación de la utilidad diagnóstica de la versión española del cuestionario al informador «AD8»☆

PubMed Central

Pardo, C. Carnero; de la Vega Cotarelo, R.; Alcalde, S. López; Aparicio, C. Martos; Carrillo, R. Vílchez; Gavilán, E. Mora; Galvin, J.E.

2012-01-01

Introducción El AD8 es un cuestionario al informador breve que puede ser autoaplicado y facilita la identificación de deterioro cognitivo (DC); nuestro objetivo es evaluar la utilidad diagnóstica (UD) de una versión española. Material y métodos Estudio transversal en una muestra clínica de díadas paciente/ informador, 330 sujetos con sospecha de DC o demencia (DEM) y 71 controles. Se ha evaluado la consistencia interna (α de Cronbach) y la validez (correlaciones parciales con estadio GDS, Fototest e índice funcional [IF]). La UD se ha evaluado para no DC vs DC (GDS 3–4) por medio del área bajo la curva ROC (aROC) y se ha considerado mejor punto de corte aquel que hacía máximo el índice de Youden. Resultados En la muestra, 105 no tenían DC, 99 tenían DC sin DEM y 203 DEM. La consistencia interna es alta (α 0,90, IC del 95%, 0,89–0,92), al igual que las correlaciones con GDS (r = 0,72, p < 0,001), Fototest (r = −0,61, p < 0,001) e IF (r = 0,59, p < 0,001). El aROC del AD8 es 0,90 (IC del 95%, 0,86–0,93), sin diferencia significativa con la del Fototest (aROC 0,93, IC del 95%, 0,89–0,96); el mejor punto de corte es 3/4 con sensibilidad de 0,93 (IC del 95%, 0,88–0,96), especificidad de 0,81 (IC del 95%, 0,72–0,88) y el 88,8% de las clasificaciones correctas. El uso conjunto de AD8 y Fototest mejora de forma significativa la UD de ambos (aROC 0,96, IC del 95%, 0,93–0,98, p < 0,05). Conclusiones La versión española del AD8 conserva las cualidades psicométricas y la UD de la versión original; su uso combinado con el Fototest mejora de forma significativa la UD de ambos. PMID:22652137

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

PubMed Central

Ren, Hong Yu; Grove, Diane E.; De La Rosa, Oxana; Houck, Scott A.; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J.; Cyr, Douglas M.

2013-01-01

Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR. PMID:23924900

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.

PubMed

Ren, Hong Yu; Grove, Diane E; De La Rosa, Oxana; Houck, Scott A; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J; Cyr, Douglas M

2013-10-01

Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR.

Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

PubMed

Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

2016-12-01

Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

Genetic modifiers of CHEK2*1100delC associated breast cancer risk

PubMed Central

Muranen, Taru A.; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D.P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Bojesen, Stig E.; Nordestgaard, Børge G.; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V.; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Peto, Julian; dos Santos Silva, Isabel; Couch, Fergus J.; Olson, Janet E.; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor J.; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W.M.; Fasching, Peter A.; Beckmann, Matthias W.; Andrulis, Irene L.; Knight, Julia A.; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G.; Milne, Roger L.; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L.; Southey, Melissa C.; John, Esther M.; Whittemore, Alice S.; Bolla, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F.; Schmidt, Marjanka K.; Nevanlinna, Heli

2016-01-01

Purpose CHEK2*1100delC is a founder variant in European populations conferring a 2–3 fold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods With genotype data of 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results The PRS conferred an odds ratio (OR) of 1.59 [95% CI 1.21–2.09] per standard deviation for BC for CHEK2*1100delC carriers and 1.58 [1.55–1.62] for non-carriers. No evidence for deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 [0.86–4.78] for CHEK2*1100delC carriers placing them to the high risk category according to UK NICE guidelines. OR for the lowest quintile was 0.52 [0.16–1.74], indicating life-time risk close to population average. Conclusion Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify the carriers at a high life-time risk for clinical actions. PMID:27711073

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

PubMed

Muranen, Taru A; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Bojesen, Stig E; Nordestgaard, Børge G; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Investigators, Nbcs; Peto, Julian; Dos Santos Silva, Isabel; Couch, Fergus J; Olson, Janet E; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K; Cox, Angela; Cross, Simon S; Sawyer, Elinor J; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W M; Fasching, Peter A; Beckmann, Matthias W; Andrulis, Irene L; Knight, Julia A; Investigators, kConFab/Aocs; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G; Milne, Roger L; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L; Southey, Melissa C; John, Esther M; Whittemore, Alice S; Bolla, Manjeet K; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F; Schmidt, Marjanka K; Nevanlinna, Heli

2017-05-01

CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.

Transnationals Becoming English Teachers in Mexico: Effects of Language Brokering and Identity Formation (Transnacionales Convirtiéndose en Docentes de Inglés en México: Efectos de la Mediación Lingüística y la Formación de la Identidad)

ERIC Educational Resources Information Center

Pablo, Irasema Mora; Rivas, Leonardo Arturo Rivas; Lengeling, M. Martha; Crawford, Troy

2015-01-01

The objective of this research was to explore the effects of language brokering upon identity formation within the family unit of students who have lived in the United States for a period of time and have come back to live in Mexico. The participants are six students that are currently undertaking a BA in TESOL (Teaching of English to Speakers of…

DELIVERING TIMELY AIR QUALITY, TRAFFIC, AND WEATHER INFORMATION TO YOUR COMMUNITY/THE PASO DEL NORTE ENVIRONMENTAL MONITORING PROJECT

EPA Science Inventory

EPA has developed a technology transfer handbook for the EMPACT Paso del Norte Project. The EMPACT Paso del Norte Environmental Monitoring Project is a mobile vehicle emissions project that involves the international community of El Paso, TX; Sundland Park, NM; and Juarez, Mexico...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION ...

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

63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION A, HIGHWAY 1. 1-DN A #124, STA. 164=00 SHOWING DRAINAGE CONDITIONS, G.F.H., 7-30-32. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

Analisis espacial de las areas protegidas terrestres de Puerto Rico

Treesearch

M. Quinones; W.A. Gould; J. Castro-Prieto; S. Martinuzzi

2013-01-01

En este mapa de investigacion describimos las areas protegidas terrestres de Puerto Rico basado en elementos naturales y antropogenicos del paisaje. Utilizamos datos geoespaciales para calcular la extension y representatividad de elementos del paisaje dentro de las areas protegidas de Puerto Rico, i.e., cobertura del terreno (Gould et al. 2007), asentamientos urbanos...

Defense.gov - Dignity, Honor, Respect - For the Fallen

Science.gov Websites

combat operation passes through Dover Air Force Base, Del. The responsibility, and honor, of preparing Operations Center. Stories Dignified Transfer Pays Tribute to Fallen DOVER AIR FORCE BASE, Del., March 12 vehicle to the Air Force Mortuary Affairs Operations Center at Dover Air Force Base, Del. Story Center

Ecuadorean-Peruvian Rivalry in the Upper Amazon,

DTIC Science & Technology

1978-01-01

8217 y el Ecuador. Documentos anexos a la Memoria del Per. Madrid, 1903. Vol. III, Document 86- p. 216 ff. 2. Jorge W. Villacres Moscoso, Historia...AMISTAD Y LIMITES ENTRE PERU Y ECUADOR Los Gobiernos del Peru’ y del Ecuador, deseando dar solucior. a la cuestic~n de Ifmites que por largo tiempo los

Ácaros del mango

USDA-ARS?s Scientific Manuscript database

Los ácaros constituyen un grupo abundante y diverso que ocupa diferentes hábitats en árboles frutales y la estructura y disposición del follaje y ramas del mango, contribuyen significativamente a que se presente gran diversidad de ácaros benéficos y dañinos asociados a esta especie frutal. En Colomb...

33 CFR 334.110 - Delaware Bay off Cape Henlopen, Del.; naval restricted area.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Del.; naval restricted area. 334.110 Section 334.110 Navigation and Navigable Waters CORPS OF....110 Delaware Bay off Cape Henlopen, Del.; naval restricted area. (a) The area. Beginning at a point on... regulations in this section shall be enforced by the Commandant, Fourth Naval District, and such agencies as...

[Recommendations to improve the scientific communication process in the Revista Médica del IMSS].

PubMed

Álvarez, Ivón

2016-01-01

In order to improve the position of the Revista Médica del Instituto Mexicano del Seguro Social among the different journals, in this editorial we enumerate a series of recommendations to ameliorate the practices of the different actors who participate in the scientific communication process of this journal.

Modeling landscapes and past vegetation patterns of New Mexico's Rio Del Oso Valley

Treesearch

Richard D. Periman

2005-01-01

Humans have interacted with the landscape and ecosystem of New Mexico's Rio del Oso Valley for thousands of years. Throughout the Holocene, various cultures have dramatically affected and altered the Rio del Oso. An interdisciplinary research approach, incorporating geomorphology, paleobotany, archaeology, and history, provides a broad range of methodologies and...

Atypical E2F transcriptional repressor DEL1 acts at the intersection of plant growth and immunity by controlling the hormone salicylic acid.

PubMed

Chandran, Divya; Rickert, Joshua; Huang, Yingxiang; Steinwand, Michael A; Marr, Sharon K; Wildermuth, Mary C

2014-04-09

In plants, the activation of immunity is often inversely correlated with growth. Mechanisms that control plant growth in the context of pathogen challenge and immunity are unclear. Investigating Arabidopsis infection with the powdery mildew fungus, we find that the Arabidopsis atypical E2F DEL1, a transcriptional repressor known to promote cell proliferation, represses accumulation of the hormone salicylic acid (SA), an established regulator of plant immunity. DEL1-deficient plants are more resistant to pathogens and slightly smaller than wild-type. The resistance and size phenotypes of DEL1-deficient plants are due to the induction of SA and activation of immunity in the absence of pathogen challenge. Moreover, Enhanced Disease Susceptibility 5 (EDS5), a SA transporter required for elevated SA and immunity, is a direct repressed target of DEL1. Together, these findings indicate that DEL1 control of SA levels contributes to regulating the balance between growth and immunity in developing leaves. Copyright © 2014 Elsevier Inc. All rights reserved.

[La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

Medición de densidades medias de meteoritos: test del método de inmersión

NASA Astrophysics Data System (ADS)

Steren, G.

Se evaluó una técnica simple para medir las densidades medias de meteoritos, basada en el Método de Arquímedes y que utiliza cuentas de vidrio de 40μ en lugar de un fluído esto presenta la ventaja de no ser intrusivo ni químicamente reactivo (D.Britt and G.Consolmagno, 1996, B.A.A.S.28,1106). El estudio, realizado en junio de este año por participantes de la VI Escuela de Verano del Observatorio del Vaticano, empleó 37 muestras de la colección del Observatorio del Vaticano, de las cuales 26 eran Condritas, 1 Pallasita y 1 Howardita; algunas de ellas ya habian sido estudiadas por otras técnicas aunque también se incluyeron muestras no estudiadas anteriormente.

[Not Available].

PubMed

Chivu, Elena Cristina; Artero-Fullana, Ana; Alfonso García, Antonio; Sánchez Juan, Carlos

2016-07-19

Introducción: conociendo la elevada prevalencia de la desnutrición hospitalaria, se hace necesaria su detección precoz. Cuando, por diversos motivos, no es posible realizar una valoración completa del estado nutricional, se recomienda el empleo de herramientas validadas de cribado nutricional. Estas ayudarían a detectar de forma rápida a aquellos pacientes que necesiten de un tratamiento nutricional.Objetivos: determinar la prevalencia del riesgo de desnutrición, en el Hospital General Universitario de Valencia, empleando para ello la herramienta de cribado nutricional HEMAN y comprobar si la implementación de esta herramienta en la práctica clínica, sería lo más adecuado.Métodos: estudio transversal, realizado sobre una muestra de 1.099 pacientes ingresados en un hospital terciario. A todos ellos se les realizó el cribado nutricional HEMAN a las 24-48 horas del ingreso. Las variables cualitativas se compararon mediante Chi-cuadrado, y las cuantitativas mediante el test t de Student.Resultados: la prevalencia del riesgo de desnutrición fue del 33,5%. Los pacientes que resultaron positivos en el cribado (HEMAN ≥ 3), tenían mayor edad que los pacientes normonutridos, referían pérdidas de peso entre el 5-10%, el 55,2% disminuyó su ingesta a menos del 50% de la habitual. Además, ingresaron con patologías consideradas de leves a moderadas. La utilización del método HEMAN como herramienta de cribado, resultó ser práctica y efectiva, y ayudó a disminuir el tiempo empleado con cada paciente encuestado evaluado.Conclusiones: se detectó una elevada prevalencia de riesgo de desnutrición entre los pacientes evaluados, por lo tanto se hace imprescindible la utilización de métodos de cribado nutricional en la rutina diaria del hospital, para ello recomendamos especialmente la utilización del método HEMAN.

Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770

PubMed Central

Gentzsch, Martina; Ren, Hong Y.; Houck, Scott A.; Quinney, Nancy L.; Cholon, Deborah M.; Sopha, Pattarawut; Chaudhry, Imron G.; Das, Jhuma; Dokholyan, Nikolay V.; Randell, Scott H.

2016-01-01

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients. PMID:27402691

Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770.

PubMed

Gentzsch, Martina; Ren, Hong Y; Houck, Scott A; Quinney, Nancy L; Cholon, Deborah M; Sopha, Pattarawut; Chaudhry, Imron G; Das, Jhuma; Dokholyan, Nikolay V; Randell, Scott H; Cyr, Douglas M

2016-09-01

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients. Copyright © 2016 the American Physiological Society.

Estudio de la fotoabsorción y fotoionización de la molécula de alta relevancia atmosférica no a través de los estados Rydberg con la metodología MQDO

NASA Astrophysics Data System (ADS)

Bustos, E.; Velasco, A. M.; Martín, I.; Lavín, C.

Los procesos de fotoionización son de una importancia fundamental [1] y encuentran aplicación en un gran número de contextos científicos: Astrofísica [2], química de las radiaciones, biología. Los investigadores de dichos campos, necesitan de valores de fiables de secciones eficaces para la fotoionización parcial, la Fotoabsorción, así como para los procesos de fotofragmentación en amplios intervalos espectrales, particularmente en estudios de modelización [3-5]. En este trabajo se ha centrado la atención sobre el oxido nítrico, que se ha considerado apropiado y relevante por varios motivos: por el trascendental papel que representa en la física y química de la alta atmosfera [6], aparte de por estar íntimamente relacionado con los problemas de contaminación. Los procesos de recombinación disociativa [7] del NO, donde los estados Rydberg se encuentran directamente implicados, son relevantes, por ejemplo, en las regiones E y F de la ionosfera [7]. En este trabajo se estudia la fotoionización del NO desde el estado fundamental con la versión molecular del método del orbital de defecto cuántico (MQDO). Para ello se calcula el diferencial de las fuerzas de oscilador parciales que constituyen los canales de fotoionización del NO desde el estado fundamental. La continuidad del diferencial de fuerza de oscilador calculada a través del umbral de fotoionización, esto es, en las regiones del espectro discreta y del continua, se adopta como criterio de calidad la escasez de datos comparativos [8].

Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

PubMed

Koc, Arzuhan; Batar, Bahadir; Celik, Ozlem; Onaran, Ilhan; Tasan, Ertugrul; Sultuybek, Gonul Kanigur

2014-07-01

Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels. Copyright © 2014 Elsevier GmbH. All rights reserved.

Manual del McVCO 1999

USGS Publications Warehouse

McChesney, P.J.

1999-01-01

El McVCO es un generador de frecuencias basado en un microcontrolador que reemplaza al oscilador controlado por voltaje (VCO) utilizado en telemetría analógica de datos sísmicas. Acepta señales de baja potencia desde un sismómetro y produce una señal subportadora modulada en frecuencia adecuada para enlaces telefónicos o vía radio a un lugar remoto de recolección de datos. La frecuencia de la subportadora y la ganancia pueden ser seleccionadas mediante un interruptor. Tiene la opción de poder operar con dos canales para la observación con ganancia alta y baja. El McVCO fue diseñado con el propósito de mejorar la telemetría analógica de las señales dentro de la Pacific Northwest Seismograph Network (PNSN) (Red Sismográfica del Noroeste del Pacífico). Su desarrollo recibió el respaldo del Programa de Geofísica de la Universidad de Washington y del "Volcano Hazards and Earthquake Hazards programs of the United States Geological Survey (USGS) (Programa de Investigaciones de Riesgos Volcánicos y Programa de Investigaciones de Riesgos Sísmicos de los EEUU). Cientos de instrumentos se han construido e instalado. Además de utilizarlo el PNSN, el McVCO es usado por el Observatorio Vulcanológico de Alaska para monitorear los volcanes aleutianos y por el USGS Volcano Disaster Assistance Program (Programa de Ayuda en las Catástrofes Volcánicas del USGS) para responder a crisis volcánicas en otros países. Este manual cubre el funcionamiento del McVCO, es una referencia técnica para aquellos que necesitan saber con más detalle cómo funciona el McVCO, y cubre una serie de temas que requieren un trato explícito o que derivan del despliegue del instrumento.

Analysis of density and epitopes of D antigen on the surface of erythrocytes from DEL phenotypic individuals carrying the RHD1227A allele.

PubMed

Gu, Juan; Sun, An-Yuan; Wang, Xue-Dong; Shao, Chao-Peng; Li, Zheng; Huang, Li-Hua; Pan, Zhao-Lin; Wang, Qing-Ping; Sun, Guang-Ming

2014-04-01

The characteristics of the D antigen are important as they influence the immunogenicity of D variant cells. Several studies on antigenic sites have been reported in normal D positive, weak D and partial D cases, including a comprehensive analysis of DEL types in Caucasians. The aim of this study was to assess D antigen density and epitopes on the erythrocyte surface of Asian type DEL phenotypic individuals carrying the RHD1227A allele in the Chinese population. A total of 154 DEL phenotypic individuals carrying the RHD1227A allele were identified through adsorption and elution tests and polymerase chain reaction analysis with sequence-specific primers in the Chinese population. D antigen density on the erythrocyte surface of these individuals was detected using a flow cytometric method. An erythrocyte sample with known D antigen density was used as a standard. Blood samples from D-negative and D-positive individuals were used as controls. In addition, D antigen epitopes on the erythrocyte surface of DEL individuals carrying the RHD1227A allele were investigated with 18 monoclonal anti-D antibodies specific for different D antigen epitopes. The means of the median fluorescence intensity of D antigen on the erythrocyte membrane surface of D-negative, D-positive and DEL individuals were 2.14±0.25, 193.61±11.43 and 2.45±0.82, respectively. The DEL samples were estimated to have approximately 22 D antigens per cell. The samples from all 154 DEL individuals reacted positively with 18 monoclonal anti-D antibodies specific for different D antigen epitopes. In this study, D antigen density on the erythrocyte surface of DEL individuals carrying the RHD1227A allele was extremely low, there being only very few antigenic molecules per cell, but the D antigen epitopes were grossly complete.

The CHEK2 del5395 is a founder mutation without direct effects for cancer risk in the latvian population.

PubMed

Plonis, J; Kalniete, D; Nakazawa-Miklasevica, M; Irmejs, A; Vjaters, E; Gardovskis, J; Miklasevics, E

2015-12-01

Our objective was to determine: 1) whether the checkpoint kinase 2 ( CHEK2 ) del5395 (g.27417113-27422508 del, NC_000022.11) is a founder mutation in the Latvian population, 2) if there is an association between CHEK2 del5395 mutation and cancer risk, and 3) and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster) as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR). The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher's exact test. All p values were two-sided and the odds ratios (OR) calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32). In control groups, the del5395 mutation was most frequent (0.76%) in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer.

Comparison among the efficacy of interventions for the return rate to receive the pap test report: randomized controlled clinical trial.

PubMed

Vasconcelos, Camila Teixeira Moreira; Pinheiro, Ana Karina Bezerra; Nicolau, Ana Izabel Oliveira; Lima, Thaís Marques; Barbosa, Denise de Fátima Fernandes

2017-03-02

to test the effects of a behavioral, an educative and a comparative intervention on women's adherence to the return appointment to receive the pap test report. randomized controlled clinical trial at a Primary Health Care Service, involving three groups: EG (educative session and test demonstration), BG (recall ribbon) and standard intervention (card containing the return appointment - graphical reminder), called comparative group here (CG). To select the sample, the following was established: having started sexual activity and undergoing the pap smear during the study, resulting in 775 women. among the 775 women, 585 (75.5%) returned to receive the test result within 65 days. The educative group presented the highest return rate (EG=82%/CG=77%/BG=66%), statistically significant only when compared to the behavioral group (p=0.000). The educative group obtained the smallest interval (p<0.05) concerning the mean number of days of return to receive the test result (EG:M=43days/BG:M=47.5days/CG:M=44.8 days). the educative group reached higher return rates and the women returned earlier, but the behavioral intervention showed to be the least effective. Brazilian Clinical Trial Register: RBR-93ykhs. testar los efectos de una intervención comportamental (GCP), educativa (GE) y otra comparativa (GCA) en la adhesión de las mujeres a la consulta de retorno para recibir el laudo de citología vaginal. estudio experimental aleatorizado controlado en una Unidad de Atención Primaria de Salud con tres grupos: GE (sesión educativa y demonstración del examen), GCP (cinta recuerdo) e intervención estándar (tarjeta con la fecha de la consulta de retorno - recuerdo gráfico), llamado de grupo comparativo (GCA). Para seleccionar la muestra, fue establecido: haber iniciado actividad sexual y hacer la citología vaginal durante el estudio, resultando en 775 mujeres. entre las 775 mujeres, 585 (75,5%) regresaron para recibir el resultado del examen con hasta 65 días. El grupo educativo presentó el mayor porcentaje de retorno (GE=82%/GCA=77%/GCP=66%), con significancia estadística sólo cuando comparado al comportamental (p=0,000). El grupo educativo alcanzó menor intervalo (p<0,05) del promedio de días de retorno para recibir el resultado del examen (GE:M=43 días/GCP:M=47,5 días/GCA:M=44,8 días). el grupo educativo alcanzó proporciones mayores de retorno, y las mujeres regresaron más precozmente, pero la intervención comportamental se mostró la menos eficaz. Registro Brasileño de Ensayo Clínico: RBR-93ykhs. testar os efeitos de uma intervenção comportamental (GCP), educativa (GE) e outra de comparação (GCA) na adesão das mulheres à consulta de retorno para receber o laudo do exame colpocitológico. estudo experimental randomizado controlado em uma Unidade de Atenção Primária à Saúde com três grupos: GE (sessão educativa e demonstração do exame), GCP (fita lembrança) e intervenção-padrão (cartão contendo a data da consulta de retorno - lembrete gráfico), aqui denominado de grupo de comparação (GCA). Para a seleção da amostra, estabeleceu-se: ter iniciado atividade sexual e realizar o exame colpocitológico durante o estudo, resultando em 775 mulheres. dentre as 775 mulheres, 585 (75,5%) retornaram para receber, o resultado do exame com até 65 dias. O grupo educativo apresentou o maior percentual de retorno (GE=82%/GCA=77%/GCP=66%), com significância estatística apenas quando comparado ao comportamental (p=0,000). O grupo educativo obteve menor intervalo (p<0,05) da média de dias de retorno para receber o resultado do exame (GE:M=43dias/GCP:M=47,5dias/GCA:M=44,8 dias) . o grupo educativo atingiu proporções maiores de retorno, e as mulheres retornaram mais precocemente, porém a intervenção comportamental mostrou-se a menos eficaz. Registro Brasileiro de Ensaio Clínico: RBR-93ykhs.

Dual-porosity modeling of groundwater recharge: testing a quick calibration using in situ moisture measurements, Areuse River Delta, Switzerland

NASA Astrophysics Data System (ADS)

Alaoui, Abdallah; Eugster, Werner

A simple method for calibrating the dual-porosity MACRO model via in situ TDR measurements during a brief infiltration run (2.8 h) is proposed with the aim of estimating local groundwater recharge (GR). The recharge was modeled firstly by considering the entire 3 m of unsaturated soil, and secondly by considering only the topsoil to the zero-flux plane (0-0.70 m). The modeled recharge was compared against the GR obtained from field measurements. Measured GR was 313 mm during a 1-year period (15 October 1990-15 October 1991). The best simulation results were obtained when considering the entire unsaturated soil under equilibrium conditions excluding the macropore flow effect (330 mm), whereas under non-equilibrium conditions GR was overestimated (378 mm). Sensitivity analyses showed that the investigation of the topsoil is sufficient in estimating local GR in this case, since the water stored below this depth appears to be below the typical rooting depth of the vegetation and is not available for evapotranspiration. The modeled recharge under equilibrium conditions for the 0.7-m-topsoil layer was found to be 364 mm, which is in acceptable agreement with measurements. Une méthode simple pour la calibration du modèle à double porosité MACRO par des mesures TDR in situ durant un bref essai d'infiltration (2.8 h) a été proposée pour l'estimation locale de la recharge de la nappe (RN). La RN a été d'abord simulée en tenant compte de toute la zone non saturée (3 m) et ensuite, en considérant uniquement la couverture du sol entre zéro et le plan du flux nul (0.70 m). La RN simulée a été comparée à la RN observée. La RN mesurée durant une année (15 octobre 1990-15 octobre 1991) était de 313 mm. Les meilleures simulations ont été obtenues en tenant compte de toute la zone non saturée sous les conditions d'équilibre excluant le flux préférentiel (330 mm). Sous les conditions de non équilibre, la RN a été surestimée (378 mm). Les analyses de sensitivité ont montré que l'investigation de la couverture du sol est suffisante pour l'estimation locale de la RN du fait que l'eau traversant le plan du flux nul se trouverait sous la zone des racines et échapperait à l'évapotranspiration. La RN simulée sur les 0.70 m du sol sous les conditions d'équilibre était de 364 mm, ce qui est comparable aux mesures. Se propone un método sencillo para calibrar el modelo de doble porosidad "MACRO" mediante medidas in-situ obtenidas por TDR durante un breve ensayo de infiltración (2,8 horas), con el objetivo de estimar la recarga local al acuífero. Ésta ha sido modelada de dos formas: considerando los 3 m de suelo no saturado y empleando sólo desde la capa superior hasta el plano de flujo nulo (de 0 a 0,70 m). Se compara la recarga modelada con la recarga local medida en campo, la cual fue de 313 mm durante un ciclo anual (del 15 de octubre de 1990 al 15 de octubre de 1991). Las mejores simulaciones corresponden a la hipótesis de columna entera no saturada en condiciones de equilibrio, excluyendo el efecto de macroporos (valor de 330 mm), mientras que el resultado obtenido para condiciones de no equilibrio en la recarga local está sobreestimado (378 mm). Los análisis de sensibilidad muestran que la investigación del horizonte superior del suelo es suficiente para estimar la recarga local en este caso, ya que el agua almacenada por debajo de esta profundidad parece estar fuera del alcance típico de las raíces de la vegetación y no puede ser evapotranspirada. La recarga modelada en condiciones de equilibrio para la capa superior de 0,70 m de espesor es de 364 mm, valor aceptable respecto a las medidas.

Weyl fermions in a family of Gödel-type geometries with a topological defect

NASA Astrophysics Data System (ADS)

Garcia, G. Q.; Oliveira, J. R. De S.; Furtado, C.

In this paper, we study Weyl fermions in a family of Gödel-type geometries in Einstein general relativity. We also consider that these solutions are embedded in a topological defect background. We solve the Weyl equation and find the energy eigenvalues and eigenspinors for all three cases of Gödel-type geometries where a topological defect is passing through them. We show that the presence of a topological defect in these geometries contributes to the modification of the spectrum of energy. The energy zero modes for all three cases of the Gödel geometries are discussed.

Observaciones del CH interestelar y el continuo en 3,3 GHz

NASA Astrophysics Data System (ADS)

Olano, C. A.; Combi, J. A.; Pöppel, W.; Benaglia, P.; Sanz, A. J.; Bava, J. A.

Se informa sobre el proyecto que se lleva a cabo en el IAR con el propósito de observar las líneas hiperfinas del estado fundamental del CH y el continuo en la banda de 3,3 GHz. El nuevo receptor construído en nuestro laboratorio para tal fin se instaló sobre uno de los radiotelescopios, funcionando conjuntamente con los sistemas de procesamiento actuales del IAR. Los resultados de las primeras observaciones, realizadas tanto en las líneas espectrales como en el continuo sobre fuentes conocidas, fueron satisfactorios.

Study of Aerospace Materials, Coatings, Adhesions and Processes. Aircraft Icing Processes. Volume 2.

DTIC Science & Technology

1984-09-14

la direccio’n del eje de la son - da. DATOS ELECTRICOS Rint’erna 20.26 . R(OC) =5.35 Q R(22 0 C).. 5.93 Q R(100 0 C) 7.43 . Roperacio’n... son las constantes de calibraci6n propias del sensor. 1INT A FN. de Informe I-231/S10/84.076Pg. . La temperatura de funcionamiento se deterrnin6 por l...funcionamiento del sensor, T la temperatura ambiente, la densidad y v la velocidad. A, B y n son las constantes de cal- z braci6n propias del

Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21.

PubMed

Yu, Jiang-Yong; Yu, Si-Fan; Wang, Shu-Hang; Bai, Hua; Zhao, Jun; An, Tong-Tong; Duan, Jian-Chun; Wang, Jie

2016-03-21

Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R mutations exhibit different responsiveness to EGFR-TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes. Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR-TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high-performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations. Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR-TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression-free survival (PFS) after first-line EGFR-TKI treatment (14.4 vs. 11.4 months, P = 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment, and there was no significant difference in the co-existence of T790M mutation with EGFR 19 del and L858R mutations before EGFR-TKI treatment (5.6% vs. 8.8%, P = 0.554) or after treatment (24.4% vs. 35.4%, P = 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes. Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R mutations. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation.

Reference Aid Abbreviations in the Latin American Press

DTIC Science & Technology

1977-08-30

FTC Frente de Trabajadores de la Cultura Frente de Trabajadores Copeyanos FTCCP Federacion de Trabajadores en Construccion Civil del Peru...Naciones Unidas ACOLSURE Asociacion Colombiana de Suboficiales de las Fuerzas Militares en Retiro ACOMINAS Aco Minas Gerais S.A. ACOPECAFE...28 CAMACOL Camara Colombiana de la Construccion CAMAS Coordinador del Area Maritima del Atlantico Sur CAME Colombian Chamber of

Discourse of His Excellency the President of the Republic of Chile, Don Eduardo Frei Ruiz-Tagle

NASA Astrophysics Data System (ADS)

1999-06-01

Es una gran satisfacción para mí inaugurar lo que será, dentro de breve tiempo, el telescopio más poderoso del mundo, que viene a responder tan claramente a la necesidad esencial del ser humano de explorar y conocer los orígenes y misterios del universo.

62. R.L.T., photographer November 1, 1934 DEL NORTE COUNTY, SECTION ...

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

62. R.L.T., photographer November 1, 1934 DEL NORTE COUNTY, SECTION D, HIGHWAY 1. REDWOOD CLEARING ON EXISTING LINE, 1-DN-71-A #26, R.L.T. 11-1-34. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

60. C.J.T., photographer December 23, 1955 KLAMATH RIVER BRIDGE, DEL ...

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

60. C.J.T., photographer December 23, 1955 KLAMATH RIVER BRIDGE, DEL NORTE COUNTY, SECTION A, HIGHWAY 1. DN-1-A #538, KLAMATH RIVER BR. FROM SO. END, 12/23/55, C.J.T. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

77 FR 2606 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to Executive Order 12978

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

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IKZF1 deletion is an independent prognostic marker in childhood B-cell precursor acute lymphoblastic leukemia, and distinguishes patients benefiting from pulses during maintenance therapy: results of the EORTC Children's Leukemia Group study 58951.

PubMed

Clappier, E; Grardel, N; Bakkus, M; Rapion, J; De Moerloose, B; Kastner, P; Caye, A; Vivent, J; Costa, V; Ferster, A; Lutz, P; Mazingue, F; Millot, F; Plantaz, D; Plat, G; Plouvier, E; Poirée, M; Sirvent, N; Uyttebroeck, A; Yakouben, K; Girard, S; Dastugue, N; Suciu, S; Benoit, Y; Bertrand, Y; Cavé, H

2015-11-01

The added value of IKZF1 gene deletion (IKZF1(del)) as a stratifying criterion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is still debated. We performed a comprehensive analysis of the impact of IKZF1(del) in a large cohort of children (n=1223) with BCR-ABL1-negative BCP-ALL treated in the EORTC-CLG trial 58951. Patients with IKZF1(del) had a lower 8-year event-free survival (EFS, 67.7% versus 86.5%; hazard ratio (HR)=2.41; 95% confidence interval (CI)=1.75-3.32; P<0.001). Importantly, despite association with high-risk features such as high minimal residual disease, IKZF1(del) remained significantly predictive in multivariate analyses. Analysis by genetic subtype showed that IKZF1(del) increased risk only in the high hyperdiploid ALLs (HR=2.57; 95% CI=1.19-5.55; P=0.013) and in 'B-other' ALLs, that is, lacking classifying genetic lesions (HR=2.22; 95% CI=1.45-3.39; P<0.001), the latter having then a dramatically low 8-year EFS (56.4; 95% CI=44.6-66.7). Among IKZF1(del)-positive patients randomized for vincristine-steroid pulses during maintenance, those receiving pulses had a significantly higher 8-year EFS (93.3; 95% CI=61.3-99.0 versus 42.1; 95% CI=20.4-62.5). Thus, IKZF1(del) retains independent prognostic significance in the context of current risk-adapted protocols, and is associated with a dismal outcome in 'B-other' ALL. Addition of vincristine-steroid pulses during maintenance may specifically benefit to IKZF1(del) patients in preventing relapses.

Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

PubMed

Chamcheu, Jean Christopher; Afaq, Farrukh; Syed, Deeba N; Siddiqui, Imtiaz A; Adhami, Vaqar M; Khan, Naghma; Singh, Sohinderjit; Boylan, Brendan T; Wood, Gary S; Mukhtar, Hasan

2013-05-01

Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses. © 2013 John Wiley & Sons A/S.

Development and validation of an automated delirium risk assessment system (Auto-DelRAS) implemented in the electronic health record system.

PubMed

Moon, Kyoung-Ja; Jin, Yinji; Jin, Taixian; Lee, Sun-Mi

2018-01-01

A key component of the delirium management is prevention and early detection. To develop an automated delirium risk assessment system (Auto-DelRAS) that automatically alerts health care providers of an intensive care unit (ICU) patient's delirium risk based only on data collected in an electronic health record (EHR) system, and to evaluate the clinical validity of this system. Cohort and system development designs were used. Medical and surgical ICUs in two university hospitals in Seoul, Korea. A total of 3284 patients for the development of Auto-DelRAS, 325 for external validation, 694 for validation after clinical applications. The 4211 data items were extracted from the EHR system and delirium was measured using CAM-ICU (Confusion Assessment Method for Intensive Care Unit). The potential predictors were selected and a logistic regression model was established to create a delirium risk scoring algorithm to construct the Auto-DelRAS. The Auto-DelRAS was evaluated at three months and one year after its application to clinical practice to establish the predictive validity of the system. Eleven predictors were finally included in the logistic regression model. The results of the Auto-DelRAS risk assessment were shown as high/moderate/low risk on a Kardex screen. The predictive validity, analyzed after the clinical application of Auto-DelRAS after one year, showed a sensitivity of 0.88, specificity of 0.72, positive predictive value of 0.53, negative predictive value of 0.94, and a Youden index of 0.59. A relatively high level of predictive validity was maintained with the Auto-DelRAS system, even one year after it was applied to clinical practice. Copyright © 2017. Published by Elsevier Ltd.

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

PubMed

De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

A New Biomarker Proxy for Palaeo-pCO2 Reconstruction in Ancient Sediments

NASA Astrophysics Data System (ADS)

Pancost, R. D.; Magness, S.; Maxwell, J. R.

2001-12-01

The carbon isotopic composition of marine organic matter has commonly been used in chemostratigraphy or as a proxy for ancient pCO2 levels. Both of these goals require that the source of organic matter be well defined, and in the case of palaeo-pCO2 investigations, the organic matter must be derived ultimately from aquatic photoautotrophs. However, additional sources, including terrestrial biomass, heterotrophs, or bacteria, can also contribute to total organic carbon (TOC). In the past decade, numerous workers have attempted to refine organic carbon isotope records using the isotopic composition of individual compounds (biomarkers) rather than the TOC. The appeal of this approach is that by examining specific biomarkers, a signal diagnostic for photoautotrophic organisms can be obtained. For compound-specific isotope analyses to be most effective, the compounds analysed must have a relatively specific source. Among the most commonly used biomarkers in palaeo-pCO2 investigations are alkenones, long-chain ketones derived exclusively from certain species of haptophyte algae. However, alkenones are absent in rocks older than the Jurassic and either absent or present in low abundances in rocks older than the Miocene. Thus, in older rocks, other biomarkers, including steranes (derived from eukaryotic sterols), phytane (presumably derived from chlorophyll), and n-alkanes (derived from algal macromolecules), are used. Unfortunately, these compounds can have alternative sources and become less reliable as isotopic proxies for photoautotrophs with increasing thermal maturity and complexity of the hydrocarbon distribution. Here we propose the use of a maleimides (1H-pyrrole-2,5-diones) as a new biomarker class for evaluating past changes in photoautotroph carbon isotopic compositions. Maleimides have three key advantages over other biomarkers in ancient rocks. First, they are degradation products of chlorophyll and have no known alternative origins in marine sediments. Second, because of their unique structure, they can be readily isolated from other organic components facilitating the determination of accurate carbon isotope ratios. Finally, the pyrrole structure is relatively stable insuring that maleimides survive even in thermally mature rocks. We have applied the analysis of maleimides to investigations of sediments from the Kupferschiefer (Permian), Vena del Gesso (Messinian) and Livello Bonarelli (Cenomanian-Turonian boundary) formations. In all three cases, the carbon isotopic compositions of selected maleimides exhibit shifts predicted by either carbonate or other biomarker carbon isotope profiles.

Características del viento en estrellas Be derivadas del perfil Hα

NASA Astrophysics Data System (ADS)

Rohrmann, R.; Cidale, L.

El estudio teórico de perfiles Hα y su variabilidad en estrellas Be ha sido frecuentemente desarrollado en base a modelos de envolturas circunestelares inhomogéneas, donde la geometría del material es responsable de la forma del perfil dependiendo de la dirección de observación. Nosotros damos una interpretación alternativa y proponemos que la mayoría de las propiedades de esta línea tienen origen en la base de un viento estelar y de una estructura cromosférica anexa a la fotósfera. Encontramos que típicos perfiles Hα en Be, como son los llamados pole-on y winebottle, pueden ser reproducidos cualitativamente sin recurrir a la existencia de una envoltura asimétrica. Analizamos como la línea Hα permite identificar la posible estructura del viento en la región donde éste se inicia.

Espectro de radiación derivado de un modelo de colapso protoestelar

NASA Astrophysics Data System (ADS)

Coca, S.; Rohrmann, R.

El exceso de emisión infrarroja en objetos protoestelares es atribuido usualmente a un disco de material en torno al cuerpo central. A pesar del avance alcanzado en la elaboración de modelos, aún existen dificultades para explicar la ley de temperatura del disco necesaria para reproducir las luminosidades y perfiles de energía observados. Nuestra propuesta consiste en determinar la distribución espectral de la radiación derivada de un particular modelo de colapso protoestelar, y estudiar la evolución del espectro desde estadíos tempranos de la contracción gravitatoria. Este plan es orientado a evaluar las propiedades del modelo (distribuciones de masa y temperatura del material circunestelar) por comparación con datos observacionales, a fin de inferir de ello los posibles ajustes requeridos en la teoría actualmente empleada.

DelPhi web server v2: incorporating atomic-style geometrical figures into the computational protocol.

PubMed

Smith, Nicholas; Witham, Shawn; Sarkar, Subhra; Zhang, Jie; Li, Lin; Li, Chuan; Alexov, Emil

2012-06-15

A new edition of the DelPhi web server, DelPhi web server v2, is released to include atomic presentation of geometrical figures. These geometrical objects can be used to model nano-size objects together with real biological macromolecules. The position and size of the object can be manipulated by the user in real time until desired results are achieved. The server fixes structural defects, adds hydrogen atoms and calculates electrostatic energies and the corresponding electrostatic potential and ionic distributions. The web server follows a client-server architecture built on PHP and HTML and utilizes DelPhi software. The computation is carried out on supercomputer cluster and results are given back to the user via http protocol, including the ability to visualize the structure and corresponding electrostatic potential via Jmol implementation. The DelPhi web server is available from http://compbio.clemson.edu/delphi_webserver.

Breast Cancer Epidemiology in Puerto Rico

DTIC Science & Technology

2013-06-30

Universidad de Puerto Rico Recinto de Ciencias Medicas Escuela Graduada de Salud Publica Apartado postal 365067, San Juan, Puerto Rico 00936-5067... Ciencias Medicas. Este proyecto recibe fondos del Programa de Investigacion de Cancer de Mama, bajo el mecanismo de Donativo para Adiestramiento en...minimo. Una enfermera adiestrada del Consorcio de Investigacion Clinica y Traslacional del Recinto de Ciencias Medicas (PRCTRC) tomara estas muestras

General nonextremal rotating charged Gödel black holes in minimal five-dimensional gauged supergravity.

PubMed

Wu, Shuang-Qing

2008-03-28

I present the general exact solutions for nonextremal rotating charged black holes in the Gödel universe of five-dimensional minimal supergravity theory. They are uniquely characterized by four nontrivial parameters: namely, the mass m, the charge q, the Kerr equal rotation parameter a, and the Gödel parameter j. I calculate the conserved energy, angular momenta, and charge for the solutions and show that they completely satisfy the first law of black hole thermodynamics. I also study the symmetry and separability of the Hamilton-Jacobi and the massive Klein-Gordon equations in these Einstein-Maxwell-Chern-Simons-Gödel black hole backgrounds.

Mejoras en la exactitud del reloj de ángulo horario del telescopio de 2,15 mts de CASLEO

NASA Astrophysics Data System (ADS)

Aballay, J. L.; Pereyra, P. F.; Marún, A. H.

Para aumentar la exactitud en el control del ángulo horario del telescopio, se está implementando el uso de un reloj con una precisión de 1/100 seg. En conjunto con el encoder que otorga la posición con un acierto de 0,012 seg. de arco, se podrá implementar otro dígito en el reloj de ángulo horario con la posibilidad de ver las décimas. Esto, sumado a la precisión ya lograda en declinación, permitirá realizar offsets con mayor exactitud.

Gödel universes in string theory

NASA Astrophysics Data System (ADS)

Barrow, John D.; Dabrowski, Mariusz P.

1998-11-01

We show that homogeneous Gödel spacetimes need not contain closed timelike curves in low-energy-effective string theories. We find exact solutions for the Gödel metric in string theory for the full O(α') action including both dilaton and axion fields. The results are valid for bosonic, heterotic and super-strings. To first order in the inverse string tension α', these solutions display a simple relation between the angular velocity of the Gödel universe, Ω, and the inverse string tension of the form α'=1/Ω2 in the absence of the axion field. The generalization of this relationship is also found when the axion field is present.

Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels.

PubMed

Kopeikin, Z; Yuksek, Z; Yang, H-Y; Bompadre, S G

2014-09-01

The most common cystic fibrosis-associated mutation, the deletion of phenylalanine 508 (F508del), results in channels with poor membrane expression and impaired function. VX-770, a clinically approved drug for treatment of CF patients carrying the G551D mutation, and VX-809, a corrector shown in vitro to increase membrane expression of mutant channels, are currently undergoing clinical trials, but functional data at the molecular level is still lacking. The effect of VX-770 and VX-809 on the multiple functional defects of F508del-CFTR was assessed via excised inside-out patch-clamp experiments. VX-770 completely restores the low opening-rate of F508del-CFTR, with smaller open-time increase, in temperature-corrected and VX-809-treated channels. The shorter locked-open time of hydrolysis-deficient F508del-CFTR is also prolonged by VX-770. VX-809 does not improve channel function by itself as previously reported. The results from these studies can be interpreted as an equilibrium shift toward the open-channel conformation of F508del-CFTR channels. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

[Bibliometric analysis of Revista Médica del IMSS in the Scopus database for the period between 2005-2013].

PubMed

García-Gómez, Francisco; Ramírez-Méndez, Fernando

2015-01-01

To analyze the number of articles of Revista Médica del Instituto Mexicano del Seguro Social (Rev Med Inst Mex Seguro Soc) in the Scopus database and describe principal quantitative bibliometric indicators of scientific publications during the period between 2005 to 2013. Scopus database was used limited to the period between 2005 to 2013. The analysis cover mainly title of articles with the title of Revista Médica del Instituto Mexicano del Seguro Social and its possible modifications. For the analysis, Scopus, Excel and Access were used. 864 articles were published during the period between 2005 to 2013 in the Scopus database. We identified authors with the highest number of contributions including articles with the highest citation rate and forms of documents cited. We also divided articles by subjects, types of documents and other bibliometric indicators which characterize the publications. The use of Scopus brings the possibility of analyze with an external tool the visibility of the scientific production published in the Revista Médica del IMSS. The use of this database also contributes to identify the state of science in México, as well as in the developing countries.

Apoyo a Estudios Geodinamicos con GPS en Guatemala

NASA Astrophysics Data System (ADS)

Robles, V. R.

2013-05-01

El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si existen diferencias graduales crecientes o decrecientes, que nos da un indicativo del desplazamiento de la corteza terrestre al rededor del volcan.

Implementación de un modelo de capacitación multimedial para brindar orientación alimentaria a los beneficiarios de un programa de ayuda social en México.

PubMed

Amaya-Castellanos, Maritza Alejandra; Morales-Ruan, María Del Carmen; Uribe-Carvajal, Rebeca; Jiménez-Aguilar, Alejandra; Salazar-Coronel, Araceli Apolonia; Martínez-Tapia, Brenda; Shamah-Levy, Teresa

2018-03-01

Introducción: Se implementó un modelo de capacitación en orientación alimentaria para la población beneficiaria y el personal operativo del Programa de Abasto Rural (PAR) de Diconsa, el cual es una iniciativa social de ayuda alimentaria que abastece productos básicos y complementarios, además de brindar capacitación en localidades de alta marginación en México. Objetivo: Documentar la utilización de la Metodología de Capacitación Multimedial (MCM) en el desarrollo de un esquema de capacitación sobre orientación alimentaria y su implementación en la población beneficiaria del PAR, a través de la propia estructura operativa del PAR. Metodología: El modelo se fundamenta en la MCM, integrada por cuatro elementos didácticos e indivisibles que conforman el paquete pedagógico multimedial (PPM), compuesto a su vez por tres videos y rotafolios, material impreso, prácticas y las relaciones interpersonales. Los ejes temáticos fueron: alimentación correcta para una vida saludable, alimentación materno-infantil, elecciones saludables y gasto familiar. El modelo fue replicado en cascada en los tres niveles operativos del PAR (responsables de capacitación, supervisores operativos y beneficiarios del PAR), con un componente de multiplicación horizontal, e implementado como piloto en cuatro estados de México. Resultados: Se observó un cambio positivo sobre los conocimientos en alimentación correcta en todos los niveles de capacitación, principalmente en los beneficiarios del PAR. La evaluación del proceso mostró conocimientos previos de los responsables de capacitación en los temas, buen desempeño como facilitadores, y habilidades de presentación y manejo del grupo de los supervisores operativos. A partir de las evaluaciones y del acompañamiento en la prueba piloto, fueron modificados las actividades, las estrategias y los materiales educativos del PPM. Conclusiones: La capacitación multimedial y la educación nutricional promueven procesos de cambio y desarrollo comunitario, posibles a través de la toma de conciencia y la puesta en práctica de acciones que favorecen la salud.

Species identification in forensic samples using the SPInDel approach: A GHEP-ISFG inter-laboratory collaborative exercise.

PubMed

Alves, Cíntia; Pereira, Rui; Prieto, Lourdes; Aler, Mercedes; Amaral, Cesar R L; Arévalo, Cristina; Berardi, Gabriela; Di Rocco, Florencia; Caputo, Mariela; Carmona, Cristian Hernandez; Catelli, Laura; Costa, Heloísa Afonso; Coufalova, Pavla; Furfuro, Sandra; García, Óscar; Gaviria, Anibal; Goios, Ana; Gómez, Juan José Builes; Hernández, Alexis; Hernández, Eva Del Carmen Betancor; Miranda, Luís; Parra, David; Pedrosa, Susana; Porto, Maria João Anjos; Rebelo, Maria de Lurdes; Spirito, Matteo; Torres, María Del Carmen Villalobos; Amorim, António; Pereira, Filipe

2017-05-01

DNA is a powerful tool available for forensic investigations requiring identification of species. However, it is necessary to develop and validate methods able to produce results in degraded and or low quality DNA samples with the high standards obligatory in forensic research. Here, we describe a voluntary collaborative exercise to test the recently developed Species Identification by Insertions/Deletions (SPInDel) method. The SPInDel kit allows the identification of species by the generation of numeric profiles combining the lengths of six mitochondrial ribosomal RNA (rRNA) gene regions amplified in a single reaction followed by capillary electrophoresis. The exercise was organized during 2014 by a Working Commission of the Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG), created in 2013. The 24 participating laboratories from 10 countries were asked to identify the species in 11 DNA samples from previous GHEP-ISFG proficiency tests using a SPInDel primer mix and control samples of the 10 target species. A computer software was also provided to the participants to assist the analyses of the results. All samples were correctly identified by 22 of the 24 laboratories, including samples with low amounts of DNA (hair shafts) and mixtures of saliva and blood. Correct species identifications were obtained in 238 of the 241 (98.8%) reported SPInDel profiles. Two laboratories were responsible for the three cases of misclassifications. The SPInDel was efficient in the identification of species in mixtures considering that only a single laboratory failed to detect a mixture in one sample. This result suggests that SPInDel is a valid method for mixture analyses without the need for DNA sequencing, with the advantage of identifying more than one species in a single reaction. The low frequency of wrong (5.0%) and missing (2.1%) alleles did not interfere with the correct species identification, which demonstrated the advantage of using a method based on the analysis of multiple loci. Overall, the SPInDel method was easily implemented by laboratories using different genotyping platforms, the interpretation of results was straightforward and the SPInDel software was used without any problems. The results of this collaborative exercise indicate that the SPInDel method can be applied successfully in forensic casework investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

PubMed Central

Van Goor, Fredrick; Hadida, Sabine; Grootenhuis, Peter D. J.; Burton, Bill; Stack, Jeffrey H.; Straley, Kimberly S.; Decker, Caroline J.; Miller, Mark; McCartney, Jason; Olson, Eric R.; Wine, Jeffrey J.; Frizzell, Ray A.; Ashlock, Melissa; Negulescu, Paul A.

2011-01-01

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50, 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR. PMID:21976485

Calidad de Imagen del Telescopio UNAM212

NASA Astrophysics Data System (ADS)

Cobos, F. J.; Teiada de Vargas, C.

1987-05-01

El telescopio UNAM2l2, del Observatorio Astronómico Nacional, situado en la Sierra de San Pedro Mártir (Baja California, México), cumplira en un futuro muy cercano siete años de uso para fines de investigación astronómica. Aunque en este tiempo no se ha efectuado un estudio sistemático acerca de su comportamiento óptico y de los factores que influyen en la calidad de las imágenes, se han realizado pruebas diversas, estudios parciales y reuniones especificas, cuyos resultados no siempre se han difundido ampliamente y generalmente no se han presentado por escrito. Es por ello que hemos creido necesario intentar una recopilación de la información existente para poder con ella establecer un diagnóstjco que, aunque no sea definitivo, sirva de base para futuros trabajos tendientes a optimizar el comportamiento óptico del telescopio. Es evidente que un buen número de las conclusiones que se presentan son resultado del trabajo de muchas personas ó de esfuerzos colectivos. Asimismo, hemos tratado de localizar información bibliográfica que pueda ser de utilidad. Nuestro objetivo primordial ha consistido en centrarnos en la óptica del telescopio y su calidad, pero también se han considerado otros aspectos que puedan afectar las imágenes obtenidas tales como: celda del primario, `seeing' local y externo, flexiones posibles en la estructura mecánica del telescopio, etc.

Uso Del Condón en Adolescentes Nahuas, un Modelo Explicativo.

PubMed

Tirado, María de Los Ángeles Meneses; Benavides-Torres, Raquel A; Navarro, Sergio Meneses; de la Colina, Juan Antonio Doncel; Rodríguez, Dora Julia Onofre; Hernández, Francisco Javier Baéz

2018-03-01

En México, la población indígena supera los siete millones de habitantes, en Puebla el grupo más representativo es el Náhuatl. Sin embargo, las condiciones de vida, salud, educación y transporte son precarias para esta población. En los adolescentes, las responsabilidades como el matrimonio, la familia y los compromisos ante la comunidad, favorecen conductas de riesgo sexual que dificultan su desarrollo económico, social y reproductivo. El objetivo fue proponer un modelo explicativo del uso del condón en adolescentes nahuas. Método. Bajo el marco de la teoría social cognitiva, el concepto de valores culturales de Leininger y el proceso de la sustracción teórica, se desarrolló este artículo. Se muestran las relaciones del modelo con las proposiciones y los factores que influyen en el uso del condón para este grupo específico. Finalmente, el modelo explica las variables de interés, los niveles de abstracción y las relaciones entre sí en el contexto náhuatl. El siguiente paso será implementar los indicadores empíricos para conocer el grado de influencia de los factores personales y ambientales hacia el uso del condón en adolescentes nahuas. Resultados que aportarán información para el desarrollo del conocimiento en enfermería y la reducción de riesgo sexual de esta población.

Clinical relevance of CHEK2 and NBN mutations in the macedonian population.

PubMed

Kostovska, I Maleva; Jakimovska, M; Kubelka-Sabit, K; Karadjozov, M; Arsovski, A; Stojanovska, L; Plaseska-Karanfilska, D

2015-06-01

Clinical importance of the most common CHEK2 (IVS2+1 G>A, 1100delC, I157T and del5395) and NBN (R215W and 657del5) gene mutations for breast cancer development in Macedonian breast cancer patients is unknown. We performed a case-control study including 300 Macedonian breast cancer patients and 283 Macedonian healthy controls. Genotyping was done using a fast and highly accurate single-nucleotide primer extension method for the detection of five mutations in a single reaction. The detection of the del5395 was performed using an allele-specific duplex polymerase chain reaction (PCR) assay. We have found that mutations were more frequent in breast cancer patients (n = 13, 4.3%) than in controls (n = 5, 1.8%), although without statistical significance. Twelve patients were heterozygous for one of the analyzed mutations, while one patient had two mutations (NBN R215W and CHEK2 I157T). The most frequent variant was I157T, found in 10 patients and four controls (p = 0.176) and was found to be associated with familial breast cancer (p = 0.041). CHEK2 1100delC and NBN 657del5 were each found in one patient and not in the control group. CHEK2 IVS2+1G>A and del5395 were not found in our cohort. Frequencies of the studied mutations are low and they are not likely to represent alleles of clinical importance in the Macedonian population.

CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

PubMed

Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E; Eigentler, Thomas; Garbe, Claus; Röcken, Martin; Hölmich, Lisbet Rosenkrantz; Schmidt, Henrik; Klyver, Helle; Bastholt, Lars; Nordestgaard, Børge G

2012-02-01

It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers were 2.01 (95% confidence interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79 (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma compared with noncarriers.

Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

PubMed

Iniesta, Maria D; Gorin, Michael A; Chien, Ling-Chen; Thomas, Samantha M; Milliron, Kara J; Douglas, Julie A; Merajver, Sofia D

2010-10-15

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted. Copyright © 2010 Elsevier Inc. All rights reserved.

Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.

PubMed

Magoulas, Pilar L; El-Hattab, Ayman W; Roy, Angshumoy; Bali, Deeksha S; Finegold, Milton J; Craigen, William J

2012-06-01

Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

Occurrence and fate of pesticides in the Argentine stretch of the Paraguay-Paraná basin.

PubMed

Etchegoyen, M A; Ronco, A E; Almada, P; Abelando, M; Marino, D J

2017-02-01

The Argentine stretch of the del Plata basin crosses regions devoted to extensive and intensive agriculture mostly with chemical pest control. The utilization of pesticides in the region has increased 900% in the last two decades associated with the introduction of biotech crops and direct-seeding techniques. Our objective was to study the occurrence, concentration, and fate of pesticides in surface water and bottom sediments of the principal tributaries and main watercourse of the Paraguay-Paraná River. We sampled 22 sites in the distal positions of the main affluents and main watercourse of the Paraná and report here results from two monitoring campaigns (2010-2012). Surface water and bottom sediments were analyzed according to standardized methods by matrix-solid-phase dispersion and liquid-liquid extraction, respectively. Twenty-three pesticide compounds were analyzed by gas chromatography. The results from both campaigns indicated a generalized but variable distribution in the concentrations detected throughout the basin. The ranges of total measured pesticide concentrations in water and sediments were, respectively, 0.004-6.62 μg/l and 0.16-221.3 μg/kg dry weight. Endosulfans, cypermethrin, and chlorpyrifos were ubiquitous compounds in both environmental compartments and quantitatively the most relevant. All concentrations detected in water were over the recommended guidelines for the protection of aquatic biota. The partitioning indicated a higher affinity for the sediments. Agricultural activity is the source of pesticide-pollution loads, transported by tributaries that reach the main watercourse and alter the quality of the aquatic ecosystem.

Photography and Neobaroque Imaginary in Julio Cortázar's "Las babas del diablo": Can the Neobaroque Name a Photograph?

ERIC Educational Resources Information Center

Hakobyan, Liana

2018-01-01

This article examines Julio Cortázar's short story "Las babas del diablo" from a visual perspective and at the intersection of Roland Barthes's ideas on photography and Severo Sarduy's theory on the Neobaroque. I propose that in "Las babas del diablo" photography and the Neobaroque--two seemingly unrelated concepts--interact…

[The diffusion of knowledge].

PubMed

Ramiro-H, Manuel; Cruz-A, Enrique

2016-01-01

Between August 19 and 21, the Feria del Libro de las Ciencias de la Salud (Healthcare Book Fair) took place in the Palacio de Medicina in Mexico City. Archives of Medical Research, Revista Médica del IMSS, and Saber IMSS, three of the main instruments of knowledge diffusion of the Instituto Mexicano del Seguro Social, assisted to this book fair, which was organized by the Facultad de Medicina of UNAM.