[(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease

Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS

Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings

Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1279-x) contains supplementary material, which is available to authorized users

Presence of pharmaceutical contaminants of emerging concerns in two rivers of western Cuba and their relationship with the extracellular enzymatic activity of microbial communities

En los últimos años ha aumentado la preocupación derivada de la presencia de contaminantes emergentes en el medio ambiente y los posibles efectos en la trilogía One Health. Este estudio determinó la concentración de contaminantes farmacéuticos de creciente preocupación y su relación con la actividad enzimática extracelular de comunidades microbianas de dos ríos del occidente de Cuba. Se analizaron dos estaciones de muestreo; uno en el Río Almendares (urbano) y otro en el Río San Juan (rural), teniendo en cuenta los focos de contaminación que llegan a estas estaciones y caracterizaciones fisicoquímicas previas. Se determinaron las actividades de proteasa extracelular, fosfatasa ácida, fosfatasa alcalina, lipasa y catalasa en agua y sedimentos y se correlacionaron con contaminantes de interés emergente determinados mediante cromatografía líquida con espectrometría de masas. Este estudio evidenció la presencia de diferentes contaminantes farmacéuticos encontrados en las categorías de antihipertensivos, estimulantes, antiinflamatorios y antibióticos en ambos ríos. Las concentraciones de contaminantes de creciente preocupación fueron mayores en el río Almendares en comparación con el río San Juan. Además, mediante el análisis de redundancia canónica se documentó la influencia de estos contaminantes en las actividades enzimáticas extracelulares de las comunidades microbianas, donde en la mayoría de los casos inhiben las actividades de proteasa, fosfatasa y lipasa y potencian la actividad de catalasa en respuesta al estrés oxidativo. La presente investigación constituye el primer reporte en Cuba de la presencia de contaminantes farmacéuticos de preocupación emergente y uno de los pocos trabajos que existen en la región latinoamericana.In recent years, the concern derived from the presence of emerging contaminants in the environment and the possible effects on the One Health trilogy has increased. This study determined the concentration of pharmaceutical contaminants of emerging concern and their relationship with the extracellular enzymatic activity of microbial communities from two rivers in western Cuba. Two sampling stations were analyzed; one in the Almendares River (urban) and the other in the San Juan River (rural), taking into account the pollution sources that arrive at these stations and previous physicochemical characterizations. Extracellular protease, acid phosphatase, alkaline phosphatase, lipase, and catalase activities in water and sediments were determined and correlated with contaminants of emerging concern determined by liquid chromatography with mass spectrometry. This study evidenced the presence of different pharmaceutical contaminants found in the categories of antihypertensives, stimulants, anti-inflammatories, and antibiotics in both rivers. Concentrations of contaminants of emerging concern were greater in the Almendares River compared to the San Juan River. In addition, through the canonical redundancy analysis, the influence of these contaminants on the extracellular enzymatic activities of microbial communities was documented, where in most cases they inhibit protease, phosphatase, and lipase activities and enhance catalase activity in response to oxidative stress. The present investigation constitutes the first report in Cuba of the presence of pharmaceutical contaminants of emerging concern and one of the few works that exist in the Latin American region.Fundación de la Universidad de Alcalá de Henare

Junction profiles of sub keV ion implantation for deep sub-quarter micron devices

Junction profiles of sub keV ion implantation for deep sub-quarter micron device

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead