Draft Genome Sequence of Antarctic Methanogen Enriched from Dry Valley Permafrost

A genomic reconstruction belonging to the genus Methanosarcina was assembled from metagenomic data from a methane-producing enrichment of Antarctic permafrost. This is the first methanogen genome reported from permafrost of the Dry Valleys and can help shed light on future climate-affected methane dynamics

Integrative Neuropsychological Characteristics of Subcortical-Frontal Brain Regions as a Schizophrenia Liability Factor

Para estudiar las características de las regiones cerebrales subcórtico-frontal, se investigaron la función y la evaluación de su relación con la vulnerabilidad a la esquizofrenia en 59 pacientes y 23 controles, empleando los métodos neuropsicológicos de Luria. El análisis estableció anormalidades bilaterales de la función de las zonas lobulares prefrontal y frontal profunda en pacientes comparados con los controles. Estas anormalidades eran más predominantes en el hemisferio izquierdo. Las coeficientes de correlación punto-biserial de algunos indicadores neuropsicológicos integrativos con la vulnerabilidad a la esquizofrenia eran de 0,39 ± 0,11 y 0,28 ± 0,09, respectivamente. Los datos obtenidos llevan a la discusión de los indicadores neuropsicológicos integrativos de regiones subcortical-frontales del cerebro que se revelan como marcadores potenciales de vulnerabilidad a la esquizofrenia y confirma el papel de la asimetría estructural y funcional del cerebro en la patogénesis de la esquizofrenia.In order to study neuropsychological characteristics of subcortical-frontal brain regions function and assessment of their relation with vulnerability to schizophrenia 59 patients and 23 controls were investigated using Luria’s neuropsychological methods. The analysis established bilateral abnormalities of the function of prefrontal and profound frontal lobe zones in patients as compared with controls. These abnormalities were more predominate in the left hemisphere. Point biserial correlation coefficients of determined integrative neuropsychological indicators with liability to schizophrenia were 0.39 ± 0.11 and 0.28 ± 0.09, for the left and right brain zones respectively. The obtained data permits discussion of the integrative neuropsychological indicators of subcorticalfrontal brain regions as potential markers of liability to schizophrenia and confirms the role of structural and functional brain asymmetry in the pathogenesis of schizophrenia

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs