447 research outputs found

    Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

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    Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

    Thermal and mechanical properties of hemp fabric-reinforced nanoclay-cement nano-composites

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    The influence of nanoclay on thermal and mechanical properties of hemp fabric-reinforced cement composite is presented in this paper. Results indicate that these properties are improved as a result of nanoclay addition. An optimum replacement of ordinary Portland cement with 1 wt% nanoclay is observed through improved thermal stability, reduced porosity and water absorption as well as increased density, flexural strength, fracture toughness and impact strength of hemp fabric-reinforced nanocomposite. The microstructural analyses indicate that the nanoclay behaves not only as a filler to improve the microstructure but also as an activator to promote the pozzolanic reaction and thus improve the adhesion between hemp fabric and nanomatrix

    Genetic Diversity, Morphological Uniformity and Polyketide Production in Dinoflagellates (Amphidinium, Dinoflagellata)

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    Dinoflagellates are an intriguing group of eukaryotes, showing many unusual morphological and genetic features. Some groups of dinoflagellates are morphologically highly uniform, despite indications of genetic diversity. The species Amphidinium carterae is abundant and cosmopolitan in marine environments, grows easily in culture, and has therefore been used as a ‘model’ dinoflagellate in research into dinoflagellate genetics, polyketide production and photosynthesis. We have investigated the diversity of ‘cryptic’ species of Amphidinium that are morphologically similar to A. carterae, including the very similar species Amphidinium massartii, based on light and electron microscopy, two nuclear gene regions (LSU rDNA and ITS rDNA) and one mitochondrial gene region (cytochrome b). We found that six genetically distinct cryptic species (clades) exist within the species A. massartii and four within A. carterae, and that these clades differ from one another in molecular sequences at levels comparable to other dinoflagellate species, genera or even families. Using primers based on an alignment of alveolate ketosynthase sequences, we isolated partial ketosynthase genes from several Amphidinium species. We compared these genes to known dinoflagellate ketosynthase genes and investigated the evolution and diversity of the strains of Amphidinium that produce them

    A Tractable Experimental Model for Study of Human and Animal Scabies

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    Scabies, a neglected parasitic disease caused by the microscopic mite Sarcoptes scabiei, is a major driving force behind bacterial skin infections in tropical settings. Aboriginal and Torres Strait Islander peoples are nearly twenty times more likely to die from acute rheumatic fever and rheumatic heart disease than individuals from the wider Australian community. These conditions are caused by bacterial pathogens such as Group A streptococci, which have been linked to underlying scabies infestations. Community based initiatives to reduce scabies and associated disease have expanded, but have been threatened in recent years by emerging drug resistance. Critical biological questions surrounding scabies remain unanswered due to a lack of biomedical research. This has been due in part to a lack of either a suitable animal model or an in vitro culture system for scabies mites. The pig/mite model reported here will be a much needed resource for parasite material and will facilitate in vivo studies on host immune responses to scabies, including relations to associated bacterial pathogenesis, and more detailed studies of molecular evolution and host adaptation. It represents the missing tool to extrapolate emerging molecular data into an in vivo setting and may well allow the development of clinical interventions

    First light of VLT/HiRISE: High-resolution spectroscopy of young giant exoplanets

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    A major endeavor of this decade is the direct characterization of young giant exoplanets at high spectral resolution to determine the composition of their atmosphere and infer their formation processes and evolution. Such a goal represents a major challenge owing to their small angular separation and luminosity contrast with respect to their parent stars. Instead of designing and implementing completely new facilities, it has been proposed to leverage the capabilities of existing instruments that offer either high-contrast imaging or high-dispersion spectroscopy by coupling them using optical fibers. In this work, we present the implementation and first on-sky results of the High-Resolution Imaging and Spectroscopy of Exoplanets (HiRISE) instrument at the Very Large Telescope (VLT), which combines the exoplanet imager SPHERE with the recently upgraded high-resolution spectrograph CRIRES using single-mode fibers. The goal of HiRISE is to enable the characterization of known companions in the H band at a spectral resolution on the order of R = λ/∆λ = 100 000 in a few hours of observing time. We present the main design choices and the technical implementation of the system, which is constituted of three major parts: the fiber injection module inside of SPHERE, the fiber bundle around the telescope, and the fiber extraction module at the entrance of CRIRES. We also detail the specific calibrations required for HiRISE and the operations of the instrument for science observations. Finally, we detail the performance of the system in terms of astrometry, temporal stability, optical aberrations, and transmission, for which we report a peak value of ~3.9% based on sky measurements in median observing conditions. Finally, we report on the first astrophysical detection of HiRISE to illustrate its potential

    First light of VLT/HiRISE: High-resolution spectroscopy of young giant exoplanets

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    A major endeavor of this decade is the direct characterization of young giant exoplanets at high spectral resolution to determine the composition of their atmosphere and infer their formation processes and evolution. Such a goal represents a major challenge owing to their small angular separation and luminosity contrast with respect to their parent stars. Instead of designing and implementing completely new facilities, it has been proposed to leverage the capabilities of existing instruments that offer either high contrast imaging or high dispersion spectroscopy, by coupling them using optical fibers. In this work we present the implementation and first on-sky results of the HiRISE instrument at the very large telescope (VLT), which combines the exoplanet imager SPHERE with the recently upgraded high resolution spectrograph CRIRES using single-mode fibers. The goal of HiRISE is to enable the characterization of known companions in the HH band, at a spectral resolution of the order of R=λ/Δλ=100 000R = \lambda/\Delta\lambda = 100\,000, in a few hours of observing time. We present the main design choices and the technical implementation of the system, which is constituted of three major parts: the fiber injection module inside of SPHERE, the fiber bundle around the telescope, and the fiber extraction module at the entrance of CRIRES. We also detail the specific calibrations required for HiRISE and the operations of the instrument for science observations. Finally, we detail the performance of the system in terms of astrometry, temporal stability, optical aberrations, and transmission, for which we report a peak value of ∼\sim3.9% based on sky measurements in median observing conditions. Finally, we report on the first astrophysical detection of HiRISE to illustrate its potential.Comment: 17 pages, 15 figures, 3 tables. Submitted to A&A on 19 September 202
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