Three new Alpha1-Antitrypsin deficiency variants help to define a C-Terminal region regulating conformational change and polymerization

Alpha1-antitrypsin (AAT) deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema. The most common genetic AAT variants found in patients are the mildly deficient S and the severely deficient Z alleles, but several other pathogenic rare alleles have been reported. While the plasma AAT deficiency is a common trait of the disease, only a few AAT variants, including the prototypic Z AAT and some rare variants, form cytotoxic polymers in the endoplasmic reticulum of hepatocytes and predispose to liver disease. Here we report the identification of three new rare AAT variants associated to reduced plasma levels and characterize their molecular behaviour in cellular models. The variants, called Mpisa (Lys259Ile), Etaurisano (Lys368Glu) and Yorzinuovi (Pro391His), showed reduced secretion compared to control M AAT, and accumulated to different extents in the cells as ordered polymeric structures resembling those formed by the Z variant. Structural analysis of the mutations showed that they may facilitate polymerization both by loosening ‘latch’ interactions constraining the AAT reactive loop and through effects on core packing. In conclusion, the new AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant. The new mutations cluster structurally, thus defining a region of the AAT molecule critical for regulating its conformational state

Funcionamiento ejecutivo temprano en niños con dificultades matemáticas persistentes

El objetivo del presente estudio consistió en examinar las diferencias en las funciones ejecutivas de inhibición y memoria de trabajo (MT) evaluadas en Educación Infantil entre sujetos con dificultades persistentes en el área de matemáticas en 2º de Educación Primaria y niños con un rendimiento adecuado. La muestra final del estudio estuvo conformada por 180 niños (inicialmente compuesta por 209 preescolares), de los cuales un 6.6% presentaron dificultades matemáticas persistentes (n = 12) y el 45.5% mostraron un rendimiento adecuado en ambas mediciones (n = 82). En Educación Infantil, se administraron seis tareas neuropsicológicas relacionadas con las funciones ejecutivas de inhibición, MT verbal y MT viso-espacial. Los resultados evidenciaron diferencias en 5 de las 6 tareas aplicadas en el primer momento de evaluación, con efectos especialmente importantes para las funciones ejecutivas de inhibición y MT verbal. Se comentan las implicaciones de estos hallazgos para la investigación y la práctica psicoeducativa.The aim of this study was to examine the differences in executive functions of inhibition and working memory (WM) assessed in kindergarten between subjects with persistent difficulties in the area of mathematics in 2nd grade of Primary School and children with typical achievement. The final study sample consisted of 180 children (originally composed of 209 preschoolers), 6.6% of whom had persistent mathematical difficulties (n = 12) and 45.5% showed average performance in both measurements (n = 82). At Kindergarten, six neuropsychological tasks related to the executive functions of inhibition, verbal WM and visuospatial WM were administered. The results showed differences in 5 of the 6 tasks applied at the first assessment, with particularly significant effects on inhibition and verbal WM. The implications of these findings for psychoeducational research and practice are discussed.El presente trabajo ha sido financiado por el Ministerio de Economía y Competitividad de España (EDU2012-37452) y la Universitat Jaume I de Castellón (beca pre-doctoral; 2I005-PREDOC/ 2013/34)

Fish β-parvalbumin acquires allergenic properties by amyloid assembly

PRINCIPLES: Amyloids are highly cross-β-sheet-rich aggregated states that confer protease resistance, membrane activity and multivalence properties to proteins, all essential features for the undesired preservation of food proteins transiting the gastrointestinal tract and causing type I allergy. METHODS: Amyloid propensity of β-parvalbumin, the major fish allergen, was theoretically analysed and assayed under gastrointestinal-relevant conditions using the binding of thioflavin T, the formation of sodium dodecyl sulphate- (SDS-) resistant aggregates, circular dichroism spectroscopy and atomic force microscopy fibril imaging. Impact of amyloid aggregates on allergenicity was assessed with dot blot. RESULTS: Sequences of β-parvalbumin from species with commercial value contain several adhesive hexapeptides capable of driving amyloid formation. Using Atlantic cod β-parvalbumin (rGad m 1) displaying high IgE cross-reactivity, we found that formation of amyloid fibres under simulated gastrointestinal conditions accounts for the resistance to acid and neutral proteases, for the presence of membrane active species under gastrointestinal relevant conditions and for the IgE-recognition in the sera of allergic patients. Incorporation of the anti-amyloid compound epigallocatechin gallate prevents rGad m 1 fibrillation, facilitates its protease digestion and impairs its recognition by IgE. CONCLUSIONS: the formation of amyloid by rGad m 1 explains its degradation resistance, its facilitated passage across the intestinal epithelial barrier and its epitope architecture as allergen.Peer Reviewe

Escolab: investigadores en el papel de divulgadores

EscoLab (http://www.escolab.cat) es una iniciativa del ICUB e IMEB del Ayuntamiento de Barcelona que brinda la oportunidad a jóvenes de interactuar con investigadores, conocer sus proyectos y participar en actividades a través de la visita sus centros de trabajo. Este estudio, realizado con la colaboración del ODC de la UAB, analiza la experiencia que ofrece Escolab para los investigadores participantes. En general, consideran que el programa funciona con éxito porque perciben que los jóvenes aprenden, se motivan, y mejoran la imagen que tienen de la ciencia. Los investigadoresdisfrutan devolviendo su conocimiento a la sociedad pero también reconocen sus limitaciones profesionales en materia de divulgación científica por lo que solicitan asesoría. Los resultados obtenidos permiten mejorar el impacto y calidad de las actividades de divulgación de EscoLab

Funcionamiento ejecutivo y rendimiento matemático: un estudio longitudinal

El objetivo del presente estudio longitudinal consistió en examinar el poder predictivo de las funciones ejecutivas de inhibición y memoria de trabajo (MT) evaluadas en Educación Infantil (T1) sobre los aspectos formales e informales del rendimiento matemático en 2º de Educación Primaria (T2). La muestra inicial estuvo conformada por 209 preescolares de 5 a 6 años, de los que un 86.12 % de los sujetos volvieron a ser evaluados en el T2 (7-8 años). En el T1, se administraron seis tareas neuropsicológicas relacionadas con las funciones ejecutivas de inhibición y MT verbal y visoespacial. En el T2, se aplicó la batería TEMA-3 (Gingsburg y Baroody, 2003) para evaluar diferentes aspectos relacionados con el rendimiento matemático. Los resultados mostraron que 5 de las 6 tareas aplicadas en Educación Infantil son capaces de predecir el rendimiento matemático posterior, con un especial peso de la MT verbal. Se comentan las implicaciones de estos hallazgos para la investigación y la práctica psicoeducativa.This longitudinal study aimed to analyze the predictive power of the executive functions of inhibition and working memory (WM) assessed at Kindergarten (T1) on the formal and informal aspects of the mathematical performance in 2nd grade of Primary School (T2). The initial sample consisted of 209 preschool children of 5-6 years old. The 86.12% of this sample was re-evaluated in the T2 (7-8 years). In the T1 six neuropsychological tasks related to the executive functions of inhibition and verbal and visuospatial WM were administered. In T2, the test TEMA-3 (Ginsburg & Baroody, 2003) was used to assess different aspects of math performance. The results showed that 5 of the 6 tasks applied in kindergarten are able to predict later math achievement, with a special weight of the verbal WM function. The implications of these findings for research and practice are discussed.El presente trabajo ha sido financiado por el Ministerio de Economía y Competitividad de España (EDU2012-37452) y la Universitat Jaume I de Castellón (beca pre-doctoral; 2I005-PREDOC/ 2013/34)