Cristales amfidinámicos y máquinas moleculares

Charla magistral sobre el estado del arte en máquinas moleculares y sus aplicacionesUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Viverrectorado de Investigación de la Universidad de Málag

Brca1 Alternative Splicing Landscape In Breast Tissue Samples

Background: BRCA1 is a key protein in cell network, involved in DNA repair pathways and cell cycle. Recently, the ENIGMA consortium has reported a high number of alternative splicing (AS) events at this locus in blood-derived samples. However, BRCA1 splicing pattern in breast tissue samples is unknown. Here, we provide an accurate description of BRCA1 splicing events distribution in breast tissue samples. Methods: BRCA1 splicing events were scanned in 70 breast tumor samples, 4 breast samples from healthy individuals and in 72 blood-derived samples by capillary electrophoresis (capillary EP). Molecular subtype was identified in all tumor samples. Splicing events were considered predominant if their relative expression level was at least the 10% of the full-length reference signal. Results: 54 BRCA1 AS events were identified, 27 of them were annotated as predominant in at least one sample. Delta 5q, Delta 13, Delta 9, Delta 5 and del 1aA were significantly more frequently annotated as predominant in breast tumor samples than in blood-derived samples. Predominant splicing events were, on average, more frequent in tumor samples than in normal breast tissue samples (P = 0.010). Similarly, likely inactivating splicing events (PTC-NMDs, Non-Coding, Delta 5 and Delta 18) were more frequently annotated as predominant in tumor than in normal breast samples (P = 0.020), whereas there were no significant differences for other splicing events (No-Fs) frequency distribution between tumor and normal breast samples (P = 0.689). Conclusions: Our results complement recent findings by the ENIGMA consortium, demonstrating that BRCA1 AS, despite its tremendous complexity, is similar in breast and blood samples, with no evidences for tissue specific AS events. Further on, we conclude that somatic inactivation of BRCA1 through spliciogenic mutations is, at best, a rare mechanism in breast carcinogenesis, albeit our data detects an excess of likely inactivating AS events in breast tumor samples

Plantas alimenticias no convencionales de una zona periurbana de Coatepec, Veracruz

Entre los recursos naturales que el hombre ha utilizado, existen las plantas alimenticias no convencionales (PANC), es decir aquellas plantas que no se cultivan o comercializan en gran cantidad, están adecuadas al medio local facilitando su cultivo e inclusive pueden ser plantas olvidadas. Cuya utilización se está desaprovechando, ya que se están perdiendo los conocimientos tradicionales acerca del uso que tienen aunado al deterioro de la vegetación primaria. Ante esta situación se planteó como objetivo de este trabajo el documentar los conocimientos tradicionales sobre las PANC en una zona periurbana de Coatepec, Ver, con lo que se busca mantener el aprovechamiento racional de éste recurso biológico. En un primer momento, para recabar la información se identificaron a informantes clave y se les aplicaron entrevistas semiestructuradas; posteriormente, se realizaron encuestas a la población del área de estudio para determinar el grado de conocimiento que tenían sobre estas plantas. Se registraron 34 especies de PANC, distribuidas en 22 familias, siendo las más representativas la familia Solanaceae con siete especies y Asteraceae con cuatro. Las personas concuerdan que este tipo de plantas son de gran importancia ya que fueron y en algunos casos siguen siendo parte de su alimentación, se reconoce que el conocimiento tradicional y uso de las mismas se resguarda en las personas mayores, por lo que es importante rescatar estos saberes y sobre todo compartirlos con las generaciones más jóvenes para que las sigan aprovechando y no se pierda su uso

Study of breast cancer incidence in patients of lymphangioleiomyomatosis

The online version of this article (doi:10.1007/s10549-016-3737-8) contains supplementary material, which is available to authorized user

Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM

Study of breast cancer incidence in patients of lymphangioleiomyomatosis

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000–2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32–5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29–9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-016-3737-8) contains supplementary material, which is available to authorized users

Diagnóstico de la capacidad de planta y planeación de la capacidad instalada para una empresa fabricante de fungicidas orgánicos

AgraQuest de México, S.A. de C.V. es una empresa dedicada a descubrir, desarrollar y comercializar productos naturales, seguros y ecológicos para el control de plagas en el hogar y el campo. El principal producto de la empresa es el biofungicida Serenade cuyo ingrediente activo es la bacteria Bacillus subtilis cepa QST713, la cual se descubrió en un rancho de California en la Unión Americana. Las bacterias de la familia Bacillus subtilis existen en los suelos y se han encontrado en una gran variedad de hábitats. Los científicos de AgraQuest Inc., encontraron que la cepa QST 713 libera sustancias de su contenido celular durante el crecimiento, con el fin de eliminar o reducir a sus competidores del entorno inmediato. El Serenade tiene un novedoso modo de actuar, antes de la infección impide que el patógeno se adhiera a la hoja, creando una zona de inhibición, restringiendo el crecimiento del patógeno bajo tiempos y condiciones estándar de aplicación. Serenade se puede aplicar incluso el mismo día de la cosecha. Un proceso patentado tanto de fabricación por fermentación como de formulación, proporcionan a Serenade propiedades excepcionales para el control de las infecciones causadas por hongos. El diagrama de flujo para el Serenade WPO (polvo) y AS (líquido) es el siguiente: (Nota: El diagrama fue omitido en esta hoja). Uno de los problemas de AgraQuest es generado por la alta dirección y por la forma de operar que tenía la empresa en sus inicios; la cual consiste en que los vendedores siempre querían contar con inventarios altos y no veían la necesidad de realizar pronósticos de acuerdo a un método matemático. Además de poder vender lo que quisieran, poco o mucho, sin tener que preocuparse si existía la suficiente producción. Mediante el análisis de tres escenarios factibles, se diagnosticará hasta que punto, la empresa podrá seguir realizando la operación de llenado de líquidos manualmente sin necesidad de invertir en una línea de llenado propia, a través de una correcta planeación de la capacidad. Nuestros objetivos específicos son: Cuantificar el mercado potencial del producto para poder encontrar parámetros confiables de penetración, para usarlos a su vez, en los distintos escenarios a considerar. Utilizar métodos de pronóstico de ventas confiables para los productos, mientras el número de datos lo permita; de lo contrario se utilizarán proyecciones con base en la fuerza de venta de la empresa. Identificar posibles cuellos de botella. Determinar la capacidad de producción de la planta. Establecer un plan de la capacidad instalada para los productos anteriormente mencionados. Determinar la fecha estimada, en caso de existir, en que los modos de producción actuales, ya no serán suficientes. La empresa no posee un plan de la capacidad a largo plazo, trayendo como consecuencia al proyecto, el realizarlo con la maquinaría que la empresa posee actualmente, y esto se conseguirá, en medida de lo posible, a través de incluir una producción continua, evitando tiempos muertos de las máquinas y los altos inventarios de producto, al mismo tiempo tener el producto disponible en el momento y en el lugar dónde se requiere. Así como también eliminar o minimizar los cuellos de botella que existan, sin invertir significativas cantidades a corto plazo

Numerical simulation since early ages of the RG8 beam test from concrack benchmark by means of a 3D fibre frame model

This work presents the numerical analysis of the RG8 test performed by the French research program Concrack2 in 2011. It consisted in a large RC beam specimen loaded in bending after restrained shrinkage. The specimen is composed of a central thinner part and two massive heads linked by two cylindrical struts that restrained strains due to thermal effects and autogenous shrinkage occurring in the concrete central part. After 8 weeks, the beam was loaded near to its ultimate capacity. The numerical model is based on the 3D fibre beam approach, capable of reproducing the response since early ages. The cross-section is discretized into fibres to take into account the different maturity levels within the crosssection. The analysis is divided into three phases: i) the thermal analysis determines the development of temperatures due to cement hydration and heat transfer, solar radiation and night cooling effects, ii) nonlinear mechanical analysis for early ages including creep, autogenous shrinkage and ageing and iii) nonlinear mechanical analysis for loading phase includes the interaction of normal and shear forces. Performance is compared against experimentation and the development of early age stresses discussed.Postprint (published version

Photolysis of an asymmetrically substituted diazene in solution and in the crystalline state

In this work we study the product distribution in the steady state photolysis of a diazene, (1-biphenyl-4-yl-1-methyl-ethyl)-tert-butyl diazene, and a ketone, 2,4-bis(biphenyl-4-yl)-2,4-dimethyl-pentan-3-one, in the solid state and in solution. The two compounds yield 1-biphenyl-4-yl-1-methyl-ethyl (BME) radicals upon photolysis. The ketone yields two units of this radical, whereas the diazene yields one BME and one tert-butyl radical. Product analysis of the two compounds in solution makes it possible to differentiate their origin from their corresponding geminate cages, and from the different encounter pairs in the case of the asymmetrically substituted diazene photolysis. In this way we obtain a complete reaction scenery for the diazene, a compound with interesting features as a radical photoinitiator and as a cage effect probe in fluid media. The reaction in cages containing two BME radicals shows a decrease by a factor of 4 in the ratio of combination to disproportionation products upon going from the solid to the liquid phase. On the contrary, the reaction in cages containing a BME and a tert-butyl radical shows a 30-fold increase in combination to disproportionation ratio in liquid compared to the crystal. We analyze the reasons for these differences considering the differences in the reactivity of the radicals and in cage rigidity.Fil: Hoijemberg, Pablo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Karlen, Steven D.. University of California at Los Angeles; Estados UnidosFil: Sanramé, Carlos Norberto. University of California at Los Angeles; Estados UnidosFil: Aramendia, Pedro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: García Garibay, Miguel Angel. University of California at Los Angeles; Estados Unido

Numerical simulation since early ages of the RG8 beam test from concrack benchmark by means of a 3D fibre frame model

This work presents the numerical analysis of the RG8 test performed by the French research program Concrack2 in 2011. It consisted in a large RC beam specimen loaded in bending after restrained shrinkage. The specimen is composed of a central thinner part and two massive heads linked by two cylindrical struts that restrained strains due to thermal effects and autogenous shrinkage occurring in the concrete central part. After 8 weeks, the beam was loaded near to its ultimate capacity. The numerical model is based on the 3D fibre beam approach, capable of reproducing the response since early ages. The cross-section is discretized into fibres to take into account the different maturity levels within the crosssection. The analysis is divided into three phases: i) the thermal analysis determines the development of temperatures due to cement hydration and heat transfer, solar radiation and night cooling effects, ii) nonlinear mechanical analysis for early ages including creep, autogenous shrinkage and ageing and iii) nonlinear mechanical analysis for loading phase includes the interaction of normal and shear forces. Performance is compared against experimentation and the development of early age stresses discussed