Functional characterizations of BRAF mutations in multiple myeloma

Activating BRAF mutations are frequently found in diverse types of cancer, including multiple myeloma. Moreover, current targeted therapy can abrogate mutant BRAF kinase activity although drug resistance mechanisms are still a challenge. However, this mutation has not been functionally characterized in multiple myeloma and biological consequences along BRAF inhibitor resistance mechanisms are unknown. Here we show that BRAF V600E expression in multiple myeloma leads to an active MAPK/ERK pathway and eventual DNA damage. This mutation can be targeted with BRAF inhibitors (BRAFi). Nevertheless, we demonstrate that BRAF wild type under BRAFi leads to paradoxical activation. To overcome this effect a MEK inhibitor was employed for an effective pathway abrogation in multiple myeloma. Furthermore, to identify mechanisms that contribute to BRAFiresistance, whole exome sequencing of a BRAFi-resistance model of MM was performed. We identified a novel mutation in the transcription factor EGR-1 followed by its protein functional characterization. This showed that the mutant protein (p. 332fs) along the wild type protein is overexpressed in our in vitro model and mutant EGR-1 influences its own subcellular localization. Overexpression of the mutant EGR-1 conferred complete resistance to BRAF inhibition

The Quantum Superstring as a WZNW Model with N=2 Superconformal Symmetry

We present a new development in our approach to the covariant quantization of superstrings in 10 dimensions which is based on a gauged WZNW model. To incorporate worldsheet diffeomorphisms we need the quartet of ghosts (b_{zz},c^{z}, \b_{zz}, \g^{z}) for topological gravity. The currents of this combined system form an N=2 superconformal algebra. The model has vanishing central charge and contains two anticommuting BRST charges, Q_{S}=Q_{W} + \oint \g^{z} b_{zz} + \oint \eta_{z} and Q_{V} = \oint c^{z} \Big(T^{W}_{zz} + {1\over 2} T^{top}_{zz}\Big) + \g^{z} (B^{W}_{zz} + {1\over 2} B^{top}_{zz} \Big), where $\eta_{z}$ is obtained by the usual fermionization of \b_{zz}, \g^{z}. Physical states form the cohomology of $Q_{S}+Q_{V}$, have nonnegative grading, and are annihilated by $b_{0}$ and $\beta_{0}$. We no longer introduce any ghosts by hand, and the formalism is completely Lorentz covariant.Comment: 26 pages, harmvac; major additions and new result

Free Volatile Compounds of cv. Pedro Giménez (Vitis vinifera L.) White Grape Must Grown in San Juan, Argentina

The free aromatic composition of must from Pedro Giménez grapes, grown in San Juan, Argentina, was characterised. Samples from the vintages of 2008 and 2009 were analysed by gas chromatography–mass spectrometry–solid phase microextraction (GC–MS–SPME). Higher alcohols, terpenes, C13-norisoprenoids, esters, aldehydes and ketones were quantified. The calculation of the odour activity values (OAVs) revealed that β-damascenone, α-ionone, β-linalool, geraniol, ethyl butanoate, hexanoate and octanoate were the most prevalent aroma-active compounds of the grape variety. However, the remaining 42 aromatic compounds that registered OAVs less than 1 could potentially contribute to the flavour of Pedro Giménez grapes. The measured monoterpene levels indicate that the Pedro Giménez grape can be considered a neutral variety.  This is the first report describing the main potential free aroma contributors of Pedro Giménez grapes in two consecutive years

Systematics of M-theory spinorial geometry

We reduce the classification of all supersymmetric backgrounds in eleven dimensions to the evaluation of the supercovariant derivative and of an integrability condition, which contains the field equations, on six types of spinors. We determine the expression of the supercovariant derivative on all six types of spinors and give in each case the field equations that do not arise as the integrability conditions of Killing spinor equations. The Killing spinor equations of a background become a linear system for the fluxes, geometry and spacetime derivatives of the functions that determine the spinors. The solution of the linear system expresses the fluxes in terms of the geometry and specifies the restrictions on the geometry of spacetime for all supersymmetric backgrounds. We also show that the minimum number of field equations that is needed for a supersymmetric configuration to be a solution of eleven-dimensional supergravity can be found by solving a linear system. The linear systems of the Killing spinor equations and their integrability conditions are given in both a timelike and a null spinor basis. We illustrate the construction with examples.Comment: 46 pages. v2: systematics of a null spinor basis is included in section

Monitoring of killer yeast populations in mixed cultures: influence of incubation temperature of microvinifications samples

Killer yeasts are frequently used to combat and prevent contamination by wild-type yeasts during wine production and they can even dominate the wine fermentation. Stuck and sluggish fermentations can be caused by an unbalanced ratio of killer to sensitive yeasts in the bioreactor, and therefore it is important to determine the proportion of both populations. The aim of this study was to provide a simple tool to monitor killer yeast populations during controlled mixed microvinifications of killer and sensitive Saccharomyces cerevisiae. Samples were periodically extracted during vinification, seeded on Petri dishes and incubated at 25 and 37 °C; the latter temperature was assayed for possible inactivation of killer toxin production. Colonies developed under the described conditions were randomly transferred to killer phenotype detection medium. Significant differences in the killer/sensitive ratio were observed between both incubation temperatures in all microvinifications. These results suggest that 37 °C seems a better option to determine the biomass of sensitive yeasts, in order to avoid underestimation of sensitive cells in the presence of killer yeasts during fermentations. Incubation at a toxin-inhibiting temperature clearly showed the real ratio of killer to sensitive cells in fermentation systems.Fil: Maturano, Yolanda Paola. Universidad Nacional de San Juan. Instituto de Biotecnología; ArgentinaFil: Nally, María Cristina. Universidad Nacional de San Juan. Instituto de Biotecnología; ArgentinaFil: Toro, María Eugenia. Universidad Nacional de San Juan. Instituto de Biotecnología; ArgentinaFil: Castellanos de Figueroa, Lucía Inés. PROIMI; Argentina. Universidad Nacional de Tucumán. FBQyF; ArgentinaFil: Combina, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vazquez, Fabio. Universidad Nacional de San Juan. Instituto de Biotecnología; Argentin

Modelo de conciencia para la sustentabilidad

Roughly, the conscience for sustainability unveils a process of civil self-management in the face of the absence or inefficiency of state management in terms of resource supply and quality of public services. In this sense, the present work set out to establish a model for the study of the phenomenon. Documentary work was done with a sample selection of sources indexed to national repositories, considering the year of publication and the keywords. Lines related to the extension of the model, as well as to the comparison between regions are confirmed to corroborate the findings reported in the literature.Grosso modo, la conciencia para la sustentabilidad devela un proceso de autogestión civil frente a la ausencia o ineficiencia de la gestión estatal en materia de abastecimiento de recursos y calidad de los servicios públicos. En ese tenor, el presente trabajo se propuso establecer un modelo para el estudio del fenómeno. Se realizó un trabajo documental con una selección muestral de fuentes indexadas a repositorios nacionales, considerando el año de publicación y las palabras claves. Se advierten líneas concernientes a la extensión del modelo, así como a la comparación entre regiones para corroborar los hallazgos reportados en la literatura

Free Volatile Compounds of cv. Pedro Giménez (Vitis vinifera L.) White Grape Must Grown in San Juan, Argentina

The free aromatic composition of must from Pedro Giménez grapes, grown in San Juan, Argentina, was characterised. Samples from the vintages of 2008 and 2009 were analysed by gas chromatography–mass spectrometry–solid phase microextraction (GC–MS–SPME). Higher alcohols, terpenes, C13-norisoprenoids, esters, aldehydes and ketones were quantified. The calculation of the odour activity values (OAVs) revealed that β-damascenone, α-ionone, β-linalool, geraniol, ethyl butanoate, hexanoate and octanoate were the most prevalent aroma-active compounds of the grape variety. However, the remaining 42 aromatic compounds that registered OAVs less than 1 could potentially contribute to the flavour of Pedro Giménez grapes. The measured monoterpene levels indicate that the Pedro Giménez grape can be considered a neutral variety. This is the first report describing the main potential free aroma contributors of Pedro Giménez grapes in two consecutive years.EEA MendozaFil: Maturano, Yolanda Paola. Universidad Nacional de San Juan. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nally, María Cristina. Universidad Nacional de San Juan. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Assof, Mariela Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Laboratorio de Aromas y Sustancias Naturales; ArgentinaFil: Toro, María Eugenia. Universidad Nacional de San Juan. Instituto de Biotecnología; ArgentinaFil: Castellanos de Figueroa, Lucía Inés. PROIMI; Argentina. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jofre, Viviana Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Laboratorio de Aromas y Sustancias Naturales; ArgentinaFil: Vazquez, Fabio. Universidad Nacional de San Juan. Instituto de Biotecnología; Argentin