Ingesta de ácidos grasos poliinsaturados de cadena larga n-3 en mujeres embarazadas

El ácido docosahexaenoico (DHA) es fundamental para el desarrollo neurológico y retiniano. La recomendación actual de DHA en el embarazo es de 200mg/d, lo cual se cubre con una o dos porciones de pescados grasos de mar por semana. 1) Evaluar la ingesta real de DHA en embarazadas. 2) Conocer el grado de información materna sobre la importancia del DHA

Development of a molecular technique for microsatellite instability for use in colon cancer

El Cáncer Colorrectal (CCR) es la segun-da causa de muerte por cáncer en Argentina, con más de 11.000 nuevos casos por año. Entre el 3 y el 8% de los casos son producidos por mutaciones heredables. El síndrome más común es el Síndrome de Lynch o Cán-cer Colorrectal Hereditario no Polipósico (CCHNP). Los pacientes afectados tienen un riesgo superior al 80% de desarrollar cáncer de colon y en mujeres, el riesgo de cáncer de endometrio es de 60%. También se encuentra incrementado el riesgo de padecer cáncer de estómago, ovario, intestino delgado, vías biliares y riñón. La patogé-nesis del CCHNP se relaciona con fallas en el sistema de reparación del ADN que lleva a la acumulación de muta-ciones de nucleótido único y cambios en la longitud de secuencias repetitivas, fenómeno conocido como Inesta-bilidad de Microsatélites (MSI). Alta Inestabilidad de mi-crosatélites (MSI-High) se presenta en más del 85% de casos de CCHNP. Además, puede detectarse en el 10-15% de los casos de CCR no asociados a CCHNP debido a metilación de los genes de las enzimas de reparación del ADN. Los tumores colorrectales con MSI tienen carac-terísticas histológicas definidas, mejor pronóstico que los tumores sin MSI y diferente respuesta a la quimioterapia. El descubrimiento de MSI en CCR ha incrementado el co-nocimiento de la diversidad de los CCR y colabora en el diagnóstico, tratamiento y asesoramiento genético. Objetivo: diseñar una técnica molecular para el análisis de MSI de bajo costo y adecuar los algoritmos para me-jorar el diagnóstico de Síndrome de Lynch en la región

Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients

MLPA en el estudio de desórdenes genómicos

El término de desórdenes genómicos se utiliza para definir aquellas condiciones que surgen por inestabilidad en la molécula de ADN y, que ocasionan, rearreglos cromosómicos que involucran regiones de uno o varios pares de megabases. Estos rearreglos determinan la pérdida, ganancia o disrupción de genes cuya expresión fenotípica varía de acuerdo a la cantidad de secuencia codificante presente (dosage- sensitive- genes). Estas anormalidades genómicas surgen predominantemente durante eventos de recombinación no alélica entre cromosomas homólogos (NAHR), aunque otros mecanismos también han sido descriptos. Los rearreglos cromosómicos ocurren en puntos de quiebra que concentran regiones inestables de la molécula de ADN como lo son las secuencias repetidas llamadas LCRs (low copy repeats) que sirven como sustrato de recombinación o los sitios palindrómicos ricos en adenina- timina. Entre los desórdenes originados por alteración en la estructura genómica se cita al síndrome de deleción/duplicación 22q11.2, que incluye varios cuadros clínicos con superposición de rasgos fenotípicos. Se estima que la variabilidad clínica en estos pacientes es consecuente con la cantidad de secuencia codificante presente en relación al tamaño de la deleción/ duplicación. El advenimiento de nuevas técnicas moleculares permite actualmente determinar con precisión el segmento delecionado/ duplicado. Una nueva metodología conocida como MLPA (multiplex ligation probe amplification) podría discriminar, para este desorden en particular, cambios en el número de copias genómicas responsables de los diferentes fenotipos. Se considera que la técnica de MLPA es una herramienta de diagnóstico complementaria, con una alta sensibilidad y especificidad en el diagnóstico de desórdenes genómicos, que permite cuantificar microdeleciones/ microduplicaciones no objetivables por otros métodos. Se espera en un futuro que el conocimiento en cuanto a los complejos mecanismos de producción de los diferentes desórdenes genómicos permita definir con claridad la existencia de una relación genotipo- fenotipo que pueda delinear a aquellas entidades con fenotipos intermedios.Fil: Ramírez, Jésica. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Echeverría, María. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Marino, Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de ADNFil: Gallardo, A.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de CardiologíaFil: Triguy, J.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de CardiologíaFil: Schroh, A.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de InmunologíaFil: Arce, Cecilia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Marzese, Diego. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Calderón, Enrique. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Vargas, Ana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética

Dinosaur bonebed amber from an original swamp forest soil

Dinosaur bonebeds with amber content, yet scarce, offer a superior wealth and quality of data on ancient terrestrial ecosystems. However, the preserved palaeodiversity and/or taphonomic characteristics of these exceptional localities had hitherto limited their palaeobiological potential. Here, we describe the amber from the Lower Cretaceous dinosaur bonebed of Ariño (Teruel, Spain) using a multidisciplinary approach. Amber is found in both a root layer with amber strictly in situ and a litter layer mainly composed of aerial pieces unusually rich in bioinclusions, encompassing 11 insect orders, arachnids, and a few plant and vertebrate remains, including a feather. Additional palaeontological data¿charophytes, palynomorphs, ostracods¿ are provided. Ariño arguably represents the most prolific and palaeobiologically diverse locality in which fossiliferous amber and a dinosaur bonebed have been found in association, and the only one known where the vast majority of the palaeontological assemblage suffered no or low-grade pre-burial transport. This has unlocked unprecedentedly complete and reliable palaeoecological data out of two complementary windows of preservation¿the bonebed and the amber¿from the same site

Cardiac and placental mitochondrial characterization in a rabbit model of intrauterine growth restriction

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication. METHODS: Hearts and placentas from 16 IUGR-offspring and 14 controls were included to characterize mitochondrial function. RESULTS: Enzymatic activities of complexes II, IV and II + III in IUGR-hearts (-11.96 ± 3.16%; -15.58 ± 5.32%; -14.73 ± 4.37%; p < 0.05) and II and II + III in IUGR-placentas (-17.22 ± 3.46%; p < 0.005 and -29.64 ± 4.43%; p < 0.001) significantly decreased. This was accompanied by a not significant reduction in CI-stimulated oxygen consumption and significantly decreased complex II SDHB subunit expression in placenta (-44.12 ± 5.88%; p < 0.001). Levels of mitochondrial content, Coenzyme Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in IUGR-hearts (-39.02 ± 4.35%; p < 0.001), but not significantly increased in IUGR-placentas. Sirtuin3 protein expression significantly increased in IUGR-hearts (84.21 ± 31.58%; p < 0.05) despite conserved anti-oxidant SOD2 protein expression and activity in both tissues. CONCLUSIONS: IUGR is associated with cardiac and placental mitochondrial CII dysfunction. Up-regulated expression of Sirtuin3 may explain attenuation of cardiac oxidative damage and preserved ATP levels under CII deficiency. GENERAL SIGNIFICANCE: These findings may allow the design of dietary interventions to modulate Sirtuin3 expression and consequent regulation of mitochondrial imbalance associated with IUGR and derived cardiovascular remodeling

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Protocatechuate 4,5-dioxygenase from Comamonas testosteroni T-2 : biochemical and molecular properties of a new subgroup within class III of extradiol dioxygenases

Comamonas testosteroni T-2 degraded at least eight aromatic compounds via protocatechuate (PCA), whose extradiol ring cleavage to 2-hydroxy-4-carboxymuconate semialdehyde (HCMS) was catalysed by PCA 4,5-dioxygenase (PmdAB). This inducible, heteromultimeric enzyme was purified. It contained two subunits, alpha (PmdA) and beta (PmdB), and the molecular masses of the denatured proteins were 18 kDa and 31 kDa, respectively. PCA was converted stoichiometrically to HCMS with an apparent K(m) of 55 muM and at a maximum velocity of 1.5 mukat. Structure-activity-relationship analysis by testing 16 related compounds as substrate for purified PmdAB revealed an absolute requirement for the vicinal diol and for the carboxylate group of PCA. Besides PCA, only 5'-hydroxy-PCA (gallate) induced oxygen uptake. The N-terminal amino acid sequence of each subunit was identical to the corresponding sequences in C. testosteroni BR6020, which facilitated sequencing of the pmdAB genes in strain T-2. Small differences in the amino acid sequence had significant effects on enzyme stability. Several homologues of pmdAB were found in sequence databases. Residues involved in substrate binding are highly conserved among the homologues. Their sequences grouped within the class III extradiol dioxygenases. Based on our biochemical and genetic analyses, we propose a new branch of the heteromultimeric enzymes within that class