FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

Entamoeba lysyl-tRNA synthetase contains a cytokine-like fomain with chemokine activity towards human endothelial cells

Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis.

Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.

Aspectos ambientales implicados en la construcción de la identidad en una muestra de adolescentes de la Universidad Intercultural de Chiapas

The general aim of this paper is to explore and illustrate the role of the physical and psychological surrounding in narrative making ofthe personal identity. A qualitative study is put forward. It consists of a reduced version of the autobiographical multi-methodology(Bagnoli, 2004). That has been applied to a sample of six students of the Universidad Intercultural de Chiapas. The specific goals are: a) to illustrate, through citations obtained from interviews and graphical material, the theoretical concepts of attachment to theplace (Pol, 2002; Vidal y colaboradores, 2004) and community sense (Kim y Kaplan, 2004); and b) to detect the most relevantfactors of such concepts manifested in the students. Data was analyzed through the Atlas.ti computer program, version 5.0 (Muñoz, 2005). The findings suggest that sense of connection and participation in the community (action - transformation) has been observed as the most significant factors in our studied sample

Los determinantes sociales del pensamiento: ni anomalismo ni funcionalización

El principal objetivo del presente trabajo es indagar si las habituales tentativas por descifrarel pensamiento desde un punto de vista sociológico, a pesar de su vehemente compromisoantirreduccionista, podrían aceptar en último término la reducción de ideas, argumentos y doctrinasa sus presuntos determinantes sociales. En una primera etapa analizamos el ¿sociologismoanómalo¿ de Martin Kusch, señalamos algunas de sus lagunas, y establecemos que la panopliaconceptual en losofía de la mente es fértilmente aplicable al ámbito racional-social. A continuaciónconsideramos el funcionalismo reduccionista de Jaegwon Kim, nos centramos en latesis de que los estados intencionales de la mente, al contrario de lo que ocurre con los qualia,son causalmente funcionalizables, e intentamos establecer sus posibles repercusiones en la interpretaciónsocial del pensamiento. La aplicación de la metodología funcionalista al horizonteracional-social, de todos modos, parece venir desmentida por la evidencia, ya que las propiedadesdel pensamiento equiparables a los qualia son de hecho eminentemente funcionalizablesen la medida que fundamentan la efectividad social de los recursos gurativos y retóricos. Enun sentido análogo, la obra de Hans Blumenberg demuestra que los inescrutables ingredientes gurativos de todo pensamiento que él denomina ¿metáforas absolutas¿ son tan decisivos paracualquier proceso abstractivo que los conceptos nunca llegan a agotar su alcance determinador.Con lo cual los conceptos y las ideas más generales, antes considerados del todo funcionalizables,ahora dependen de algunas metáforas básicas, aun cuando por analogía con los qualia selas creía inmunes a toda funcionalización. Por tanto parece que la reducción no puede resolverlas di cultades que plantean los presuntos ¿determinantes sociales del pensamiento¿. Al mismotiempo, y con rmando así algunos emergentismos, los aspectos causal-funcionales del ámbitoracional-social dan la impresión de ser inconciliables con la enigmática estructura causal queponen de mani esto las aproximaciones losó cas al problema mente-cuerpo.

Efficient image mosaicing for multi-robot visual underwater mapping

Robotic platforms have advanced greatly in terms of their remote sensing capabilities, including obtaining optical information using cameras. Alongside these advances, visual mapping has become a very active research area, which facilitates the mapping of areas inaccessible to humans. This requires the efficient processing of data to increase the final mosaic quality and computational efficiency. In this paper, we propose an efficient image mosaicing algorithm for large area visual mapping in underwater environments using multiple underwater robots. Our method identifies overlapping image pairs in the trajectories carried out by the different robots during the topology estimation process, being this a cornerstone for efficiently mapping large areas of the seafloor. We present comparative results based on challenging real underwater datasets, which simulated multi-robot mapping