Classification of unknown primary tumors with a data-driven method based on a large microarray reference database

We present a new method to analyze cancer of unknown primary origin (CUP) samples. Our method achieves good results with classification accuracy (88% leave-one-out cross validation for primary tumors from 56 categories, 78% for CUP samples), and can also be used to study CUP samples on a gene-by-gene basis. It is not tied to any a priori defined gene set as many previous methods, and is adaptable to emerging new information

Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.Peer reviewe

LGI2 Truncation Causes a Remitting Focal Epilepsy in Dogs

Peer reviewe

Proyecto de pre factibilidad para la implementación de una planta de concreto seco premezclado

El presente estudio tiene como objetivo fundamental evaluar la factibilidad de implementar una planta de concreto seco premezclado, la cual surge a partir de ofrecer una propuesta ideal e integral, ante todo práctica y sencilla, un producto alternativo a lo ya existente, está dirigido para todas aquellas personas que requieran edificar, ampliar o remodelar sus viviendas. En el capítulo inicial se efectuaron estudios en donde se determinaron los antecedentes relacionados con el proyecto así como también fundamentos teóricos importantes para el respaldo conceptual del desarrollo del proyecto. El desarrollo del estudio y análisis del mercado se determinó que existe demanda potencial con relación a la oferta existente. Además se analizó la competencia y se plantearon las estrategias de comercialización que deben realizarse para la introducción del producto. En cuanto al estudio técnico (ingeniería del proyecto), se determinó el tamaño, ubicación, infraestructura, distribución de las áreas y espacios a través de métodos como Guerchet, factores ponderados, análisis de proximidad entre aéreas, así como también procesos de generación del producto a través de los diagramas de flujo , operaciones y análisis de procesos , asimismo requerimiento de materiales , personal , entre otros. Por último la inversión que necesita el proyecto, se especifica en el capítulo estudio financiero, detallados en los estados financieros como: estado de resultados, flujo caja; éste último sirviendo de base para la evaluación financiera correspondiente; asimismo el punto de equilibrio y el análisis de sensibilidad, estudio que permite determinar si el proyecto es viable y rentable en el tiempo

First Analysis of a Bacterial Collagen-Binding Protein with Collagen Toolkits: Promiscuous Binding of YadA to Collagens May Explain How YadA Interferes with Host Processes▿ †

The Yersinia adhesin YadA mediates the adhesion of the human enteropathogen Yersinia enterocolitica to collagens and other components of the extracellular matrix. Though YadA has been proposed to bind to a specific site in collagens, the exact binding determinants for YadA in native collagen have not previously been elucidated. We investigated the binding of YadA to collagen Toolkits, which are libraries of triple-helical peptides spanning the sequences of type II and III human collagens. YadA bound to many of them, in particular to peptides rich in hydroxyproline but with few charged residues. We were able to block the binding of YadA to collagen type IV with the triple-helical peptide (Pro-Hyp-Gly)10, suggesting that the same site in YadA binds to triple-helical regions in network-forming collagens as well. We showed that a single Gly-Pro-Hyp triplet in a triple-helical peptide was sufficient to support YadA binding, but more than six triplets were required to form a tight YadA binding site. This is significantly longer than the case for eukaryotic collagen-binding proteins. YadA-expressing bacteria bound promiscuously to Toolkit peptides. Promiscuous binding could be advantageous for pathogenicity in Y. enterocolitica and, indeed, for other pathogenic bacteria. Many of the tightly binding peptides are also targets for eukaryotic collagen-binding proteins, and YadA was able to inhibit the interaction between selected Toolkit peptides and platelets. This leads to the intriguing possibility that YadA may interfere in vivo with host processes mediated by endogenous collagen-binding proteins