An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies

Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases. This research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases.This work was supported by funds from MINECO-FEDER (TIN2016–81041-R to E.R.), European Human Brain Project SGA2 (H2020-RIA 785907 to M.J.S.), Junta de Andalucía (BIO-302 to F.J.E.) and MEIC (Systems Medicine Excellence Network, SAF2015–70270-REDT to F.J.E.)

Gemini-GRACES high-quality spectra of Kepler evolved stars with transiting planets: I. Detailed characterization of multi-planet systems Kepler-278 and Kepler-391

Aims. Kepler-278 and Kepler-391 are two of the three evolved stars known to date on the red giant branch (RGB) to host multiple short-period transiting planets. Moreover, the planets orbiting Kepler-278 and Kepler-391 are among the smallest discovered around RGB stars. Here we present a detailed stellar and planetary characterization of these remarkable systems. Methods. Based on high-quality spectra from Gemini-GRACES for Kepler-278 and Kepler-391, we obtained refined stellar parameters and precise chemical abundances for 25 elements. Nine of these elements and the carbon isotopic ratios, 12C∕ 13C, had not previously been measured. Also, combining our new stellar parameters with a photodynamical analysis of the Kepler light curves, we determined accurate planetary properties of both systems. Results. Our revised stellar parameters agree reasonably well with most of the previous results, although we find that Kepler-278 is ~15% less massive than previously reported. The abundances of C, N, O, Na, Mg, Al, Si, S, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, and Ce, in both stars, are consistent with those of nearby evolved thin disk stars. Kepler-391 presents a relatively high abundance of lithium (A(Li)NLTE = 1.29 ± 0.09 dex), which is likely a remnant from the main-sequence phase. The precise spectroscopic parameters of Kepler-278 and Kepler-391, along with their high 12C∕ 13C ratios, show that both stars are just starting their ascent on the RGB. The planets Kepler-278b, Kepler-278c, and Kepler-391c are warm sub-Neptunes, whilst Kepler-391b is a hot sub-Neptune that falls in the hot super-Earth desert and, therefore, it might be undergoing photoevaporation of its outer envelope. The high-precision obtained in the transit times allowed us not only to confirm Kepler-278c's TTV signal, but also to find evidence of a previously undetected TTV signal for the inner planet Kepler-278b. From the presence of gravitational interaction between these bodies we constrain, for the first time, the mass of Kepler-278b (Mp = 56 -13+37 M⊕ ) and Kepler-278c (Mp = 35 -21+9.9 M⊕ ). The mass limits, coupled with our precise determinations of the planetary radii, suggest that their bulk compositions are consistent with a significant amount of water content and the presence of H2 gaseous envelopes. Finally, our photodynamical analysis also shows that the orbits of both planets around Kepler-278 are highly eccentric (e ~ 0.7) and, surprisingly, coplanar. Further observations (e.g., precise radial velocities) of this system are needed to confirm the eccentricity values presented here.Fil: Jofré, Edgardo. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Departamento de Astrofísica Estelar; Argentina. Universidad Nacional Autónoma de México; México. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Almenara, J.M.. Universidad de Ginebra; SuizaFil: Petrucci, Romina Paola. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Departamento de Astrofísica Estelar; Argentina. Universidad Nacional Autónoma de México; México. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Gómez Maqueo Chew, Y.. Universidad Nacional Autónoma de México; MéxicoFil: Martioli, E.. Laboratorio Nacional de Astrofísica; BrasilFil: Ramírez, I.. Tacoma Community College; Estados UnidosFil: García, Luciano Héctor. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Departamento de Astrofísica Estelar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Saffe, Carlos. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Universidad Nacional de San Juan. Instituto de Ciencias Astronómicas, de la Tierra y del Espacio; ArgentinaFil: Canul, E. F.. Universidad Nacional Autónoma de México; MéxicoFil: Buccino, Andrea Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Gómez, Marcos Javier. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Departamento de Astrofísica Estelar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Moreno Hilario, E.. Universidad Nacional Autónoma de México; Méxic

Secretory immunoglobulin A (s-IgA) reactivity to acute psychosocial stress in children and adolescents: The influence of pubertal development and history of maltreatment.

Background: Mucosal secretory immunoglobulin A (s-IgA) is an antibody protein-complex that plays a crucial role in immune first defense against infection. Although different immune biomarkers have been associated with stress-related psychopathology, s-IgA remains poorly studied, especially in youth. Objectives: The present study investigated how s-IgA behaves in front of acute psychosocial stress in children and adolescents, including possible variability associated with developmental stage and history of childhood maltreatment (CM). Methods: 94 children and adolescents from 7 to 17 years (54 with a current psychiatric diagnostic and 40 healthy controls) drawn from a larger Spanish study were explored (EPI-Young Stress Project). To assess biological reactivity, participants provided five saliva samples during an acute laboratory-based psychosocial stressor, the Trier Social Stress Test for Children (TSST-C). Samples were assayed for s-IgA, as well as for cortisol. Pubertal development was ascertained by Tanner stage and CM following TASSCV criteria. Results: We observed s-IgA fluctuations throughout the stressor, indicating the validity of TSST-C to stimulate s-IgA secretion (F(4,199) = 6.200, p <.001). Although s-IgA trajectories followed a reactivity and recovery pattern in adolescents, children exhibited no s-IgA response when faced with stress (F(4,197) = 3.406, p =.010). An interaction was found between s-IgA and CM (F(4,203) = 2.643, p =.035). Interestingly, an interaction between developmental stage, CM history and s-IgA reactivity was identified (F(12,343) = 2.036, p =.017); while children non-exposed to maltreatment exhibited no s-IgA changes to acute stress, children with a history of CM showed a similar response to adolescents, increasing their s-IgA levels after the psychosocial stressor. Conclusion: Acute psychosocial stress stimulates s-IgA secretion, but only after puberty. However, children with a history of maltreatment exhibited a response resembling that of adolescents, suggesting an early maturation of the immune system. Further studies are needed to clarify the validity of s-IgA as an acute stress biomarker, including additional measures during stress exposure. Keywords: Acute stress; Adolescents; Childhood maltreatment; Children; Developmental stage; TSST-C; secretory Immunoglobulin A (s-IgA)

Actualidad y prospectiva de la investigación científica en el Centro Universitario Amecameca de la Universidad Autónoma del Estado de México

Con responsabilidad, se organizó un programa cuya finalidad fuera publicitar con transparencia dichos avances, a través de un esfuerzo de rendición de cuentas a la comunidad inmediata, la universitaria, y a la comunidad abierta, la sociedad que la principal referencia para tal efecto. El programa se concretiza a través del presente libro, conformado con una inspiración de investigación multidisciplinaria; sin embargo, para llegar a tal fin, el reto es realizar el proceso de búsqueda y generación de conocimiento transitando hacia la colaboración de los cuerpos académicos, que puedan construir nuevos conocimientos fortalecidos por la convergencia de diferentes campos del saber. En consecuencia, la primera etapa de esta estrategia es la publicidad de los trabajos investigativos ejercidos, para hacer un balance al día, pero también proyectar el futuro de cada campo y área del conocimiento. La organización explicativa está organizada por tres bloques representativos del quehacer en la generación de conocimiento del Centro Universitario, un primer bloque centra el interés en las humanidades, educación y sustentabilidad; el segundo bloque lo integra la reflexión científica sobre la construcción democrática, derechos humanos y equidad de género; en el tercer segmento se destina a la seguridad alimentaria, salud pública y sistemas agropecuarios. La actualidad de la investigación eleva la producción lograda y lo que en el momento se encuentra en construcción y los alcances que produce para la docencia, la investigación misma, y para la sociedad en general. La prospectiva es un área que todos los capítulos desarrollan con el propósito de delinear los alcances innovadores por andar en teoría, metodología e incluso en los saberes mismo

Influencia de la alimentación sobre la evolución diurna de la biosíntesis del colesterol en pollo : Efecto sobre la HMG-CoA reductasa y la composición lipidica microsomal

Se han estudiado las propiedades del enzima clave de la regulación de la biosíntesis del colesterol la hmg-coa reductasa inherentes a su condición de enzima ligado a membranas microsomales. Se ha estudiado su patrón diurno de actividad así como la velocidad total de síntesis de esteroles en hígado asa duodenal y cerebro de pollos recién nacidos poniéndose de manifiesto variaciones rítmicas diurnas en ambos parámetros de hígado e intestino. Se ha establecido asimismo sobre ellos y sobre la composición lipidica microsomal la influencia del ayuno y de una dieta suplementada con colesterol al 5% en los tres órganos poniéndose de manifiesto que el colesterol de la dieta induce descensos bruscos en la colestegenesis hepática e intestinal demasiado rápidos para poder ser explicados mediante un mecanismo exclusivo de represión de la síntesis de la hmg-coa reductasa así como cambios en la fluidez de las membranas microsomales hepáticas. Sobre la base de estos resultados se discuten los mecanismos responsables de los efectos observadosUniv. Granada, Facultad de Ciencias. Leída el 11-07-8

Characterization of a New Operon, as-48EFGH, from the as-48 Gene Cluster Involved in Immunity to Enterocin AS-48

Enterocin AS-48 is a cyclic peptide produced by Enterococcus faecalis S-48 whose genetic determinants have been identified in the conjugative plasmid pMB2. A region of 7.8 kb, carrying the minimum information required for production of and immunity against AS-48, had been previously cloned and sequenced in pAM401 (pAM401-52). In this region, the as-48A structural gene and as-48B, as-48C, as-48C(1), as-48D, and as-48D(1) genes and open reading frame 6 (ORF6) and ORF7 had been identified. The sequence analysis carried out in this work in the BglII B fragment (6.6-kb) from pMB2 cloned downstream from the last ORF identified (ORF7) revealed the existence of two new ORFs, as-48G and as-48H, necessary for full AS-48 expression. Thus, JH2-2 transformants obtained with the pAM401-81 plasmid became producers and resistant at the wild-type level. Tn5 disruption experiments in the last genes, as-48EFGH, were not able to reproduce these expression levels, confirming that expression of these genes is necessary to get the phenotype conferred by the wild-type pMB2 plasmid. The as-48EFGH operon encodes a new ABC transporter that could be involved in producer self-protection. On the basis of the observed similarities, As-48G would be the ATP-binding domain, the deduced amino acid sequences of As-48E and As48-H could be assigned as transmembrane subunits, and As-48F, with an N-terminal transmembrane segment and a coiled-coil domain, strongly resembles the structure of some known ABC transporter accessory proteins whose localization in the cell is discussed. This cluster of genes is expressed by two polycistronic mRNAs, T(2) and T(3), in JH2-2(pAM401-81) in coordinate expression. Our results also suggest that expression of T(3) could be regulated, because in JH2-2(pAM401(EH)) transformants, T(3) was not detected, suggesting that these genes do not by themselves confer immunity, in accordance with the requirement for the as-48D(1) gene for immunity against AS-48

Effectivity of Saffron Extract (Saffr&rsquo;Activ) on Treatment for Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): A Clinical Effectivity Study

Attention Deficit/Hyperactivity Disorder is the most prevalent neurodevelopmental disorder worldwide. Choice treatment includes psychostimulants, but parents tend to be reluctant to administer them due to side effects, and alternatives are needed. Saffron extract is a natural stimulant that has been proven safe and effective for treating a variety of mental disorders. This study compares the efficacy of saffron and the usual treatment with methylphenidate, using objective and pen-and-paper tests. We performed a non-randomized clinical trial with two groups, methylphenidate (n = 27) and saffron (n = 36), in children and adolescents aged 7 to 17. Results show that the efficacy of saffron is comparable to that of methylphenidate. Saffron is more effective for treating hyperactivity symptoms, while methylphenidate is more effective for inattention symptoms