916 research outputs found

    Mapping of Genetic Abnormalities of Primary Tumours from Metastatic CRC by High-Resolution SNP Arrays

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    This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic changes and the genes involved in them. [Methodology/Principal Findings]: Here we applied 500K SNP arrays to map the most common chromosomal lesions present at diagnosis in a series of 23 primary tumours from sporadic CRC patients who had developed liver metastasis. Overall our results confirm that the genetic profile of metastatic CRC is defined by imbalanced gains of chromosomes 7, 8q, 11q, 13q, 20q and X together with losses of the 1p, 8p, 17p and 18q chromosome regions. In addition, SNP-array studies allowed the identification of small (1.5 Mb) altered DNA sequences, many of which contain cancer genes known to be involved in CRC and the metastatic process. Detailed characterization of the breakpoint regions for the altered chromosomes showed four recurrent breakpoints at chromosomes 1p12, 8p12, 17p11.2 and 20p12.1; interestingly, the most frequently observed recurrent chromosomal breakpoint was localized at 17p11.2 and systematically targeted the FAM27L gene, whose role in CRC deserves further investigations. [Conclusions/Significance]: In summary, in the present study we provide a detailed map of the genetic abnormalities of primary tumours from metastatic CRC patients, which confirm and extend on previous observations as regards the identification of genes potentially involved in development of CRC and the metastatic process.This work has been partially supported by grants from the Consejeria de Sanidad, Junta de Castilla y Leon, Valladolid, Spain (SAN191/SA09/06 and SAN673/SA39/08), Fundacion Memoria de Don Samuel Solorzano Barruso, Salamanca, Spain, Caja de Burgos (Obra Social), Burgos, Spain, Grupo Excelencia de Castilla y Leon (GR37) and the RTICC from the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovacion, Madrid, Spain (RD06/0020/0035-FEDER). JM Sayagués, M Gonzalez, ME Sarasquete and MC Chillon are supported by grants (CP05/00321, FI08/00721, CA08/00212 and CA/07/00077, respectively) from the ISCIII, Ministerio de Ciencia e Innovación, Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

    A model of neuroinflammation and demyelination by intracerebroventricular injection of microbial neuraminidase

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    Comunicación en forma de poster al congresoNeuraminidase from Clostridium perfringens, which cleaves terminal sialic acid from carbohydrate chains, was injected in the lateral ventricle of rats. It diffused in the ipsilateral ventricle, the third ventricle, and also towards the periventricular brain parenchyma. Soon after, the complement system activated, and some ependymal cells detached and died. In the affected zones, there was an increased expression of GFAP in astrocytes, IBA1 in microglia, and ICAM1 in the endothelial cells of blood vessels. Cytokines, such as IL1β secreted by activated macrophages and microglia, provoked the extravasation of leucocytes from about 4 h post-injection. The main sources of cells were large venules located in the choroid plexus, the meninges and the subependyma around the foramen interventricularis. Invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last lymphocytes (mainly CD8α-positive T-lymphocytes). Leucocytes invaded the ventricle and the meninges, and also penetrated the brain parenchyma, sometimes passing through the ependyma and the glia limitans. As a result, some myelinated tracts suffered vacuolar degeneration, being the stria medullaris consistently affected. Oligodendrocytes in the damaged tracts were not affected. Vacuolated myelin recovered with time. Thus, the intracerebroventricular injection of neuraminidase may represent a novel reversible animal model to study experimental neuroinflammation and myelin vacuolization.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Ministerio de Ciencia e Innovación, SAF2010-19087; Junta de Andalucía, Consejería de Sanidad, SAS 08-0029; Junta de Andalucía, Proyecto de excelencia P-11-CVI-07637

    Enhancement of adult hippocampal neurogenesis by spatial memory training and its effect on the maintenance of cocaine-contextual memory

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    Aims:Modulation of hippocampal memories related with cocaine addiction such as cocaine-context associations could have important clinical implications. It has been asserted that learning-related experiences promote hippocampal plasticity enhancing adult hippocampal neurogenesis (AHN). Here we aimed to evaluate (1) the stimulation of AHN using a spatial learning task dependent on the hippocampus and (2) whether spatial learning reduces the long-term maintenance and reinstatement of previously acquired cocaine-associated contextual memories. Methods: Male C57BL/6J mice were first submitted to a cocaine induced conditioned place preference paradigm (CPP). Then, bromodeoxyuridine (BrdU) was administered in order to label newborn neurons. One week after the last BrdU injection, a group of mice were trained in a spatial learning task using the Morris water maze while control animals received a non-hippocampal training or stayed undisturbed in their home-cages. Twenty seven days after conditioning, mice were tested for CPP retention and extinction. Finally, a cocaine priming-induced reinstatement of drug seeking was performed. Results: Animals trained in the spatial learning task exhibited a lower long-term CPP retention memory. In addition, cocaine-induced CPP reinstatement was attenuated in trained animals. Immunohistochemistry showed an increment in the BrdU+ cells in the hippocampus of trained animals in contrast with control animals. Conclusions: Spatial memory training using the Morris water maze constitutes a tool to promote the survival of newborn neurons in the hippocampus. Furthermore, stimulation of AHN might be a neurobiological mechanism by which spatial learning reduces the long-term maintenance of previous cocaine-context associative memory. Supported by PSI2017-82604 (MICINN Spain); PSI2015-73156-JIN. Universidad de Málaga.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    A Morphological and Morphometric Dental Analysis as a Forensic Tool to Identify the Iberian Wolf (Canis Lupus Signatus)

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    Depredation by the Iberian wolf (Canis lupus signatus) is currently thought to be a problem in some areas of Spain. However, there are few technically validated forensic tools available to determine the veracity of claims with a high degree of scientific confidence, which is important given that such attacks may lead to compensation. The analysis of bite marks on attacked animals could provide scientific evidence to help identify the offender. Thus, the aim of this study was to assess the morphological and morphometric characteristics of Iberian wolf dentition. This data collection would serve as a base-point for a more accurate identification of the wolves thorough their bite marks. For the first time, 36 dental variables have been studied in wolves' skulls, employing univariate and multivariate analyses. The general morphological dental characteristics of wolves are very similar in terms of their dental formula and tooth structure to other canids, like domestic dogs. Sex differentiation was evident, principally in terms of the maxillary distance between the palatal surfaces of the canine teeth (UbC) and the width of the left mandibular canine teeth (LlCWd). New morphometric reference information was obtained that can aid the forensic identification of bite marks caused by the Iberian wolf with greater confidence

    RISK FACTORS ASSOCIATED TO SUICIDE ATTEMPT IN ADOLESCENCE. YARA 2007¬2009.

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    El suicidio, como una de las causas mas frecuentes de defunción a escala mundial, plantea un problema de gran magnitud, que justifica los esfuerzos a desarrollar por las organizaciones de salud en diferentes latitudes para prevenir y controlar los intentos suicidas en la población.  El presente trabajo aborda el estudio observacional del tipo, casos y controles, con los pacientes reportados como intento suicida entre enero del 2007 y diciembre del 2009 pertenecientes al municipio de Yara, con el objetivo de comparar la diferencia entre ellos y personas supuestamente sanas con relación a factores psicológicos, familiares, biológicas y  psicosociales esenciales de riesgo de la conducta suicida. Se estudiaron 92 pacientes y 184 personas controles. Se les aplico un cuestionario de recogida de datos diseñado al efecto, los resultados se sometieron a análisis porcentual y al estadígrafo Odd Ratio. Se concluyo que excite diferencias significativas entre las personas supuestamente sanas y con intento suicida con relaciona los factores estudiados y se encontró que los factores: manejo inadecuado del adolescente ( el mas fuertemente asociado ), depresión, violencia familiar, falta de afecto, sentimientos de desesperanza, tienen relación significativa de casualidad con la conducta suicida, mientras que los factores biológicos y psicológicos no guardan relación significativa de casualidad con esta conducta, en nuestro estudio.Suicide as one of the most frequent causes of death in the world, states a huge problem that justifies the efforts of several health organizations in different latitudes in order to prevent and control the suicide attempts in the population. This work refers to the observational research of the type, cases and controls with the patients reported as suicide attempts since January 2007 to December 2009, in Yara, with the objective to compare the difference among the patients and the apparently health people in regard to the main psychological, familiar, biologic, psychosocial risk factors of the suicide behaviour. There were analyzed 92 patients and 184 controls. There were applied a questionnaire of data developed for that purpose, the results were analyzed in percentage and in ODD ratio estadigraph.  As a conclusion it can be said that there are significant differences among apparently health people and people with suicide attempt in relation to the studied factors, and it was noticed that unappropiated adolescent handling, depression, familiar violence, lack of affection, feelings of hopeless, have a significative relation to suicide behaviour while the biological and psychological factors do not have meaningful relation to this behaviour in our research
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