The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport

Microcin J25 (MccJ25) is a cyclic peptide of 21 unmodified amino acid residues produced by a fecal strain of Escherichia coli. It has previously been shown that the antibiotic activity of this peptide is mainly directed to Enterobacteriaceae, including several pathogenic E. coli, Salmonella and Shigella strains. In this paper we show that MccJ25 acts on the cytoplasmic membrane of Salmonella newport cells producing alteration of membrane permeability, and the subsequent gradient dissipation, that initiate the inhibition of process, such as oxygen consumption. These results, taken together with our in vitro observations [Rintoul et al. (2000) Biochim. Biophys. Acta 1509, 65–72], strongly suggest that the disruption of the cytoplasmic membrane gradient is closely related to the bactericidal activity of MccJ25 in S. newport.Fil: Rintoul, Maria Regina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Fernandez, Beatriz Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Salomon, Raul Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Farias, Ricardo Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Morero, Roberto Dionisio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Ftalatos y efectos en la salud

Los plastificantes son aditivos que se mezclan con algunos plásticos, especialmente con cloruro de polivinilo (CPV) para incrementar su elasticidad. Los plastificantes de uso más común son los derivados del ácido ftálico o ftalatos. Sin embargo, al no estar químicamente ligados a la matriz plástica, los ftalatos pueden abandonar el material y provocar daños a la salud y al ambiente. Aunque, es importante considerar que actualmente no existe evidencia clara sobre su toxicidad en seres humanos, en este artículo se presenta una revisión sobre la utilización y el riesgo en el empleo de ftalatos. Se discuten también las evidencias presentadas sobre su toxicidad y con base en lo anterior se recomienda investigar la magnitud de este problema en México, país productor de PCV plastificado

The academic motivation scale-situational for college students: development and psychometric analysis

La Teoría de la Autodeterminación (TAD) reconoce diferentes tipos de motivación, a lo largo de un continuo según el grado de autorregulación del comportamiento, que operan en tres niveles de generalidad: global, contextual y situacional. Este trabajo presenta el proceso de construcción y análisis psicométricos de la Escala de Motivación Situacional Académica desarrollada a partir de las hipótesis de la TAD y del Modelo Jerárquico de la Motivación Intrínseca y Extrínseca (MJMIE). Participaron del estudio 364 estudiantes (62.6 % mujeres, 37.4 % varones) de 18 a 35 años de edad (M = 22.97, DE = 3.00) de diversas carreras de la Universidad de Buenos Aires (Argentina). Cinco jueces expertos analizaron evidencias de validez de contenido para los ítems y un grupo de alumnos aportó elementos para mejorar la validez aparente y la adecuación lingüística. Un análisis factorial exploratorio, a partir del método de Análisis Factorial de Rango Mínimo con rotación Oblimin directo, aisló una estructura trifactorial. La consistencia interna de las escalas se estimó mediante alfas ordinales, cuyos valores fueron en su totalidad adecuados. Las asociaciones significativas entre las escalas apoyaron la hipótesis teórica sobre el continuo propuesto en el modelo. Las correlaciones entre las escalas del instrumento con las de la Escala de Motivación Académica (Stover, de la Iglesia, Rial Boubeta y Fernández Liporace, 2012; Vallerand, Blais, Brierey Pelletier, 1989) fueron significativas al comparar dimensiones equivalentes y disímiles de ambas técnicas. Finalmente, se confeccionaron baremos para estudiantes universitarios locales. Los resultados, limitaciones, implicancias y líneas futuras de investigación se discuten a la luz del modelo de partida.Self Determination Theory (Deci & Ryan, 1985a) describes diverse types of motivation, situated throughout a theoretical continuum which comprises a decrease in the regulation of behaviors, from highest to lowest. These are intrinsic motivation, identified regulation, introjected regulation, external regulation, and amotivation. These types, their influential factors, mediators and outcomes, integrate a hierarchic model which entails three levels: global, contextual, and situational (Vallerand, 1997). This paper presents the design and analysis of psychometric features of the Academic Motivation Scale-Situational (AMS-S) aimed at the assessment of motivation towards specific academic activities under specific circumstances. It was developed on the grounds of the Self Determination Theory´s hypotheses as well as the Hierarchic Model of Intrinsic and Extrinsic Motivation (HMIEM) posed by Vallerand (1997). The sample was composed of 364 colleges students (62.6 % females, 37.4 % males) between 18 and 35 years old (M = 22.97, SD = 3.00) with different majors at the University of Buenos Aires (Argentine). Items were written up to represent each type of motivation formulated in the model, according to the question which must be borne in mind while responding to the scale: “Why are you at the faculty right now?” The original pool of items was evaluated by five experts in order to analyze content validity evidences. A further pilot study was performed with a small group of students, aiming at the exam of face validity evidences. The preliminary version of 44 items obtained up to then was analyzed on a standardization sample. Polychoric covariance matrices were employed once the univariate normality hypothesis was not verified for the items. The ordinal nature of data demanded such a treatment as well. The statistical package FACTOR (Lorenzo-Siva & Ferrando, 2013) was used to develop an exploratory factor analysis with minimum rank factor analysis (MRFA) extraction method followed by direct Oblimin rotation (KMO = .887; Bartlett’s Sphericity Test: χ² = 4525.6 (df = 351; p < .01). A 3-factor model which explained 68.01 % of the common variance was isolated retaining 27 items (F1 explained 18.1 %, F2, 23.2 %, and F3, 26.8 %). Regarding the items content, the extracted factors were labeled as extrinsic motivation (F1), amotivation (F2), and intrinsic motivation (F3). Additionally, internal consistency of the scales was estimated by means of ordinal alphas, with adequate coefficients in all cases (F1 = .84, F2 = .95, and F3 = .94). In order to test the self-determination continuum hypothesis entailed in the model, each dimension of the scale was correlated with the rest of them. Significant and positive associations (p < .05) were found between the adjacent scales, and negative between the non-adjacent ones, thus endorsing theoretical statements. Correlations between the scales’ scores and the similar ones of Academic Motivation Scale (Academic Motivation Scale-EMA in Spanish-Stover et al., 2012; Vallerand et al., 1989) were calculated to analyze convergent validity evidences. Significant though weak statistical associations (p < .05) were found when comparing equivalent and opposite motivational types in both tests. Finally, statistical norms to be employed with local college population were calculated. Summarizing, up to the moment the scale has achieved adequate results in terms of preliminary validity evidences and reliability, supporting its appropriate psychometric quality to be used with local college students. The main weaknesses of the study rely in the sample size, which restricts wider generalizations, as well as the lack of semi-confirmatory factor analyses and psychometric studies on stability of measures, which must be developed in further steps. The analysis of the link between situational, contextual and global measures of motivation is also strongly suggested, taking into account the reciprocal effects among them.Fil: Bruno, Flavia Eugenia. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; ArgentinaFil: Fernandez Liporace, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; ArgentinaFil: Stover, Juliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentin

Brain ethanol-metabolizing enzymes are differentially expressed in lead-exposed animals after voluntary ethanol consumption: Pharmacological approaches

Developmentally-lead (Pb)-exposed rats showed an enhanced vulnerability to the stimulating and motivational effects of ethanol (EtOH). This is accompanied by differential activity of the brain EtOH-metabolizing enzymes catalase (CAT) and mitochondrial aldehyde dehydrogenase (ALDH2). Based on the theory that brain acetaldehyde accumulation is associated with the reinforcing properties of EtOH, this study sought to determine brain CAT and ALDH2 expression in limbic areas of control and Pb-exposed animals after voluntary EtOH intake. Thirty-five-day-old rats perinatally exposed to 220 ppm Pb were offered with water or increasing EtOH solutions (2–10% v/v) during 28 days until postnatal day (PND) 63. Once intake was stable, the animals were administered: 1) saline (SAL; test days 21–24 or 21–28, as corresponds), or 2) a CAT inhibitor: 3-amine 1, 2, 4-triazole (AT; 250 mg/kg intraperitoneally [i.p.], 5 h before the last eight EtOH intake sessions -test days 21–24 and 25–28), or 3) a CAT booster: 3-nitropropionic acid (3NPA; 20 mg/kg subcutaneously [s.c.], 45 min before the last four EtOH intake sessions -test days 25–28). Two additional groups were centrally-administered cyanamide (CY, an ALDH2 inhibitor, 0.3 mg i.c.v. immediately before the last four EtOH sessions, test days 25–28) or its corresponding vehicle (VEH). Lead exposure increased EtOH intake, an effect potentiated in both groups by 3NPA or CY pretreatments and reduced by AT, albeit selectivity in the Pb group. Catalase abundance in limbic areas parallels these observations in the Pb group, showing higher CAT expression in all areas after EtOH consumption respect to the controls, an effect prevented by AT administration. In contrast, ALDH2 expression was reduced in the Pb animals after EtOH intake, with CY potentiating this effect in all brain areas under study. Based on these results and on previous evidences, we suggest that Pb exposure promotes acetaldehyde accumulation in limbic regions, providing some insights into the mechanism of action that underlies the vulnerability to the excessive EtOH consumption reported in these animals.Fil: Mattalloni, Mara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Deza Ponzio, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Albrecht, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Fernandez Hubeid, Lucia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Virgolini, Miriam Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin

Estado de saúde percebido em idosos: desigualdades regionais e sociodemográficas na Espanha

OBJECTIVE: To assess regional and sociodemographic differences in self-perceived health status among older adults. METHODS: A face-to-face quality of life survey was conducted in a representative sample of the Spanish population comprising 1,106 non-institutionalized elderly aged 60 or more in 2008. Logistic regression models were used to explain self-perceived health status according to the EuroQol Group Visual Analogue Scale (EQ-VAS). Independent variables included sociodemographic and health characteristics as well as the nomenclature of territorial units for statistics level 1 (NUTS1: group of autonomous regions) and level 2 (NUTS 2: autonomous regions). RESULTS: Younger and better off respondents were more likely to have a positive self-perceived health status. Having no chronic conditions, independence in performing daily living activities and lower level of depression were also associated with positive self-perceived health status. People living in the south of Spain showed a more negative self-perceived health status than those living in other regions. CONCLUSION: The study results point to health inequality among Spanish older adults of lower socioeconomic condition and living in the south of Spain. The analysis by geographic units allows for international cross-regional comparisons.OBJETIVO: Analisar as diferenças regionais e sociodemográficas no estado de saúde percebido por adultos mais velhos. MÉTODOS: Realizou-se um inquérito de qualidade de vida mediante entrevista pessoal com amostra representativa da população espanhola de 1.106 pessoas com 60 e mais anos não institucionalizadas, em 2008. Aplicaram-se modelos de regressão logística para explicar a saúde percebida segundo a escala visual analógica do EuroQol Group (EQ-VAS). As variáveis independentes incluíram características sociodemográficas e de saúde, assim como unidades territoriais estatísticas de nível 1 (grupo de comunidades autônomas) e nível 2 (comunidades autônomas). RESULTADOS: Os participantes dos grupos mais jovens e os que tinham uma melhor situação econômica mostraram maior probabilidade de ter uma percepção positiva da sua saúde. A ausência de problemas crônicos de saúde, a independência para realizar atividades da vida diária e menor nível de depressão também se associaram positivamente à saúde percebida como boa. Os idosos que viviam no sul mostraram uma percepção mais negativa da saúde do que as que vivem noutras regiões. CONCLUSÕES: Os resultados indicam uma desigualdade relativa no estado de saúde dos adultos mais velhos de níveis socioeconômicos inferiores e dos habitantes do sul do país. A análise por unidades territoriais estatísticas permite estabelecer comparações entre regiões em nível internacional.OBJETIVO: Analizar las diferencias regionales y sociodemográficas en el estado de salud percibido por ancianos. MÉTODOS: Se realizó una encuesta de calidad de vida mediante entrevista personal en una muestra representativa de la población española de 1.106 personas con 60 y más años no institucionalizadas en 2008. Se aplicaron modelos de regresión logística para explicar la salud percibida de acuerdo con la escala visual analógica del EuroQol Group (EQ-VAS). Las variables independientes incluyeron características sociodemográficas y de salud, así como unidades territoriales estadísticas de nivel 1 (NUTS1: grupos de comunidades autónomas), y nivel 2 (NUTS2: comunidades autónomas). RESULTADOS: Los participantes de ambos grupos, el de los más jóvenes y los que tenían una mejor situación económica, mostraron mayor probabilidad de tener una percepción positiva de la salud. La ausencia de problemas crónicos de salud, la independencia para desarrollar actividades de la vida diaria y un menor nivel de depresión también se asociaron positivamente a la salud percibida como buena. Los ancianos que vivían en el sur mostraron una percepción más negativa de su salud que aquellos que vivían en otras regiones. CONCLUSIONES: Los resultados muestran desigualdad relativa en el estado de salud de los ancianos de niveles socioeconómicos inferiores y en los habitantes del sur del país. El análisis estadístico por unidades territoriales permite establecer comparaciones entre regiones en nivel internacional

Prokaryotic diversity in ecosystems associated to minerals from the hypersaline lake Tebenquiche in the Atacama desert

The Salar de Atacama is located in the Chilean central Andes and it is a huge evaporitic system with a large number of saline water bodies in its interior. Lake Tebenquiche is one of the largest and prokaryotic microorganisms inhabiting this lake are subjected to severe conditions as high solar radiation due to a lower barometric pressure at high altitude, extreme daily temperature fluctuations, intense changes in salinity caused by net evaporation and high arsenic concentrations in the water due to volcanic events. Therefore, we decided to analyse the prokaryotic diversity of microbial mats, microbialites and one evaporite by pyrosequencing of the V4 hypervariable region of the 16S rRNA gene. In addition, the total metagenomic DNA of a microbial mat was sequenced to study the genetic and metabolic diversity for understanding the microbial processes associated to minerals in a system at high altitude. Methods: Five different samples were collected from lake Tebenquiche: two microbial mats, TebMa1 and TebMa2; two microbialites, TebMi1 and TebMi2; and one evaporite, TebEv1. The total metagenomic DNA of each sample was extracted and pyrosequenced the V4 hypervariable region of the prokaryotic 16S rRNA gene. The prokaryotic 16S rRNA amplicons were analysed using the QIIME software package. The total metagenomic DNA from microbial mat, TebMa1, was sequenced using paired-end Hi-Seq 1500 Illumina Technology and the raw reads obtained were filtered, assembled into contigs and annotated. Results: Euryarchaeota is one of the most abundant phyla in all samples studied, especially in TebEv1 with 97 % of 16S rRNA sequences. Most of the euryarchaeal OTUs are classified within the class Halobacteria or anaerobic and methanogenic archaea. Specific genes as indicators of particular biogeochemical cycles were searched in the assembled contigs of TebMa1. Nitrogenase gene sequences are found in a high amount and these sequences were aligned with a range of 70%-89% identity to known nitrogenase sequences. Phosphate is mainly obtained by two mechanisms when there is a reduced availability of phosphorous: polyphosphate metabolism and phosphate recycling. Cytoplasmic arsenate reduction and arsenite oxidation are clearly present in the arsenic-rich habitat TebMa1. Conclusions: The high conductivity measured in TebMa2 and TebEv1 must be promoting the growth of members belonging to the class Halobacteria due to the dominance of this taxon in both samples. In TebMa1, we suggest could be carried out an active biological nitrogen fixation by bacteria and archaea and due to the low percentage identity to the closest relative an important part could be novel diazotrophic microorganisms. This ecosystem is rich in arsenic and its inhabitants use arsenic resistance strategies as cytoplasmic arsenate reduction and arsenite oxidation but a possible mechanism employed by these microorganisms could be through quelation of this metalloid using polyphosphates.Fil: Fernandez, Ana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Rasuk, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Contreras, Manuel. Centro de Ecologia Aplicada; ChileFil: Novoa, Fernando. Centro de Ecologia Aplicada; ChileFil: Poire, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Visscher, Pieter T.. University of Connecticut; Estados UnidosFil: Ventosa, Antonio. Universidad de Sevilla; EspañaFil: Farias, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaXI Congreso Argentino de Microbiologia GeneralCórdobaArgentinaSociedad Argentina de Microbiología Genera

Microbial Diversity in Sediment Ecosystems (Evaporites Domes, Microbial Mats, and Crusts) of Hypersaline Laguna Tebenquiche, Salar de Atacama, Chile

We combined nucleic acid-based molecular methods, biogeochemical measurements, and physicochemical characteristics to investigate microbial sedimentary ecosystems of Laguna Tebenquiche, Atacama Desert, Chile. Molecular diversity, and biogeochemistry of hypersaline microbial mats, rhizome-associated concretions, and an endoevaporite were compared with: The V4 hypervariable region of the 16S rRNA gene was amplified by pyrosequencing to analyze the total microbial diversity (i.e., bacteria and archaea) in bulk samples, and in addition, in detail on a millimeter scale in one microbial mat and in one evaporite. Archaea were more abundant than bacteria. Euryarchaeota was one of the most abundant phyla in all samples, and particularly dominant (97% of total diversity) in the most lithified ecosystem, the evaporite. Most of the euryarchaeal OTUs could be assigned to the class Halobacteria or anaerobic and methanogenic archaea

Exposición infantil a plastificantes potencialmente tóxicos en productos de uso oral

Objetivo. Determinar la prevalencia en el uso de productos infantiles orales entre menores de tres años de edad y medir su concentración de ftalatos, sustancias potencialmente tóxicas. Material y métodos. Se realizó, en 1999, una entrevista domiciliaria a 199 madres de niños del área metropolitana de la ciudad de Toluca. Por cromatografía de gases se identificaron y cuantificaron diversos ftalatos de productos de uso oral empleados por los niños participantes y se estimó la contribución de estas fuentes a la ingesta diaria de ftalatos. Resultados. La prevalencia de uso de estos productos fue de 13%, siendo mayor entre los niños, menores de 18 meses de edad, pertenecientes al estrato socioeconómico bajo. Las concentraciones variaron desde trazas hasta 67.0% del peso. La exposición media calculada proveniente de los productos manufacturados con policloruro de vinilo y ftalatos fue de 13.94 mg/ kg de peso/día, IC 95% (9.08, 18.89). Conclusiones. La exposición a ftalatos proveniente de productos para chupar o morder se encuentra dentro de los límites reportados en otros países; sin embargo, otras fuentes pueden incrementarla. Dado que algunos ftalatos han mostrado ser tóxicos en el sistema reproductivo, y este potencial efecto es plausible en el hombre, es necesaria la investigación de otras fuentes y determinar la exposición total a través de biomarcadores

Liver X Receptor Activation with an Intranasal Polymer Therapeutic Prevents Cognitive Decline without Altering Lipid Levels

The progressive accumulation of amyloid-beta (Aβ) in specific areas of the brain is a common prelude to late-onset of Alzheimer's disease (AD). Although activation of liver X receptors (LXR) with agonists decreases Aβ levels and ameliorates contextual memory deficit, concomitant hypercholesterolemia/hypertriglyceridemia limits their clinical application. DMHCA (N,N-dimethyl-3β-hydroxycholenamide) is an LXR partial agonist that, despite inducing the expression of apolipoprotein E (main responsible of Aβ drainage from the brain) without increasing cholesterol/triglyceride levels, shows nil activity in vivo because of a low solubility and inability to cross the blood brain barrier. Herein, we describe a polymer therapeutic for the delivery of DMHCA. The covalent incorporation of DMHCA into a PEG-dendritic scaffold via carboxylate esters produces an amphiphilic copolymer that efficiently self-assembles into nanometric micelles that exert a biological effect in primary cultures of the central nervous system (CNS) and experimental animals using the intranasal route. After CNS biodistribution and effective doses of DMHCA micelles were determined in nontransgenic mice, a transgenic AD-like mouse model of cerebral amyloidosis was treated with the micelles for 21 days. The benefits of the treatment included prevention of memory deterioration and a significant reduction of hippocampal Aβ oligomers without affecting plasma lipid levels. These results represent a proof of principle for further clinical developments of DMHCA delivery systems.Fil: Navas Guimaraes, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; ArgentinaFil: Lopez Blanco, Roi. Universidad de Santiago de Compostela; EspañaFil: Correa, Juan. Universidad de Santiago de Compostela; EspañaFil: Fernandez Villamarin, Marcos. Universidad de Santiago de Compostela; EspañaFil: Bistue Millon, Maria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Kumar, Vijay. University of Colorado; Estados UnidosFil: Wempe, Michael F.. University of Colorado; Estados UnidosFil: Cuello, A. C.. McGill University; CanadáFil: Fernandez Megia, Eduardo. Universidad de Santiago de Compostela; EspañaFil: Bruno, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Medicas. Instituto de Investigacion En Ciencias Biomedicas.; Argentin

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes