105 research outputs found

    Mapping the domains of CD134 as a functional receptor for feline immunodeficiency virus (FIV)

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    The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, strains of FIV differ in their utilisation of CD134; the prototypic strain PPR, requires a minimal determinant in CRD1 of fCD134 to confer near optimal receptor function while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; substitution of amino acids S78N,S79Y,K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134 with tyrosine-79 appearing to be the critical residue for restoration of receptor function

    Mapping the domains of CD134 as a functional receptor for feline immunodeficiency virus (FIV)

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    The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, strains of FIV differ in their utilisation of CD134; the prototypic strain PPR, requires a minimal determinant in CRD1 of fCD134 to confer near optimal receptor function while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; substitution of amino acids S78N,S79Y,K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134 with tyrosine-79 appearing to be the critical residue for restoration of receptor function

    Ligand effects on gas adsorption in nanoporous phthalocyanine crystals

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    X-ray diffraction is used to study the sorption of CO and NO in two phthalocyanine nanoporous crystals (PNCs) with 4,40 bipyridine or 4,40 bipyrimidine trans coordinated to open Co2+ sites, demonstrating how the trans coordinated ligands influence the gas sorption properties and structures of the PNCs

    Beam Dynamics and First Operation of the Sub-Harmonic Bunching System in the CTF3 Injector

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    The CLIC Test Facility 3 (CTF3), built at CERN by an international collaboration, aims at demonstrating the feasibility of the CLIC scheme by 2010. The CTF3 drive beam generation scheme relies on the use of a fast phase switch of a sub-harmonic bunching system in order to phase-code the bunches. The amount of charge in unwanted satellite bunches is an important quantity, which must be minimized. Beam dynamic simulations have been used to study the problem, showing the limitation of the present CTF3 design and the gain of potential upgrades. In this paper the results are discussed and compared with beam measurements taken during the first operation of the system

    Otolith characterization and integrative species identification of adult mesopelagic fishes from the western North Atlantic Ocean

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    Fish diversity and ecology in the ocean’s mesopelagic zone are understudied compared to other marine regions despite growing interest in harvesting these potential resources. Otoliths can provide a wealth of taxonomic and life history information about fish, which can help fill these knowledge gaps; however, there has been relatively little research to date on the otoliths of mesopelagic species. Here, a species-specific image library was assembled of sagittal otoliths from 70 mesopelagic fishes belonging to 29 families collected in the western North Atlantic Ocean. Images of adult sagittal otoliths from 12 species were documented and photographed for the first time. The fish were identified to species with a combination of morphological characters and DNA barcoding. Regressions between otolith size and fish length are presented for the six species with the largest sample sizes in this study. This otolith image library, coupled with otolith-length and width to fish-length relationships, can be used for prey identification and back-calculation of fish size, making it a valuable tool for studies relating to food webs in the important yet poorly understood mesopelagic zone. In addition, the 44 fish barcodes generated in this study highlight the benefit of using an integrative taxonomic approach to studies of this nature, as well as add to existing public databases that enable cryptic species and metabarcoding analyses of mesopelagic species

    Pressure-and temperature induced phase transitions, piezochromism, NLC behaviour and pressure controlled Jahn–Teller switching in a Cu-based framework

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    In situ single-crystal diffraction and spectroscopic techniques have been used to study a previously unreported Cu-framework bis[1-(4-pyridyl)butane-1,3-dione]copper(II) (CuPyr-I). CuPyr-I was found to exhibit high-pressure and low-temperature phase transitions, piezochromism, negative linear compressibility, and a pressure induced Jahn?Teller switch, where the switching pressure was hydrostatic media dependent.The support by the Spanish Ministerio de Econom´ıa, Industria y Competitividad (PGC2018-101464-B-I00), and INNVAL 18/28 is also acknowledged

    Clinical and genetic characterization of leukoencephalopathies in adults

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    Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults

    Posterior cortical atrophy and Alzheimer’s disease : a meta-analytic review of neuropsychological and brain morphometry studies

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    This paper presents the first systematic review and meta-analysis of neuropsychological and brain morphometry studies comparing posterior cortical atrophy (PCA) to typical Alzheimer's disease (tAD). Literature searches were conducted for brain morphometry and neuropsychological studies including a PCA and a tAD group. Compared to healthy controls (HC), PCA patients exhibited significant decreases in temporal, occipital and parietal gray matter (GM) volumes, whereas tAD patients showed extensive left temporal atrophy. Compared to tAD patients, participants with PCA showed greater GM volume reduction in the right occipital gyrus extending to the posterior lobule. In addition, PCA patients showed less GM volume loss in the left parahippocampal gyrus and left hippocampus than tAD patients. PCA patients exhibit significantly greater impairment in Immediate Visuospatial Memory as well as Visuoperceptual and Visuospatial Abilities than patients with tAD. However, tAD patients showed greater impairment in Delayed Auditory/Verbal Memory than patients with PCA. PCA is characterized by significant atrophy of the occipital and parietal regions and severe impairments in visuospatial functioning.JA is funded by a doctoral grant from the Foundation for Science and Technology, FCT (SFRH/BD/64457/2009, co-funded by FSE/POPH). JA and AS are funded by project PIC/IC/83290/2007, which is supported by FEDER (POFC-COMPETE) and FCT. JMS is supported by a fellowship of the project SwitchBox-FP7-HEALTH-2010-grant 259772-2. These organizations had no role in the study design, data collection, analysis, interpretation, or in the decision to submit the paper for publication

    Visual neglect in posterior cortical atrophy

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    In posterior cortical atrophy (PCA), there is a progressive impairment of high-level visual functions and parietal damage, which might predict the occurrence of visual neglect. However, neglect may pass undetected if not assessed with specific tests, and might therefore be underestimated in PCA. In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of PCA patients

    Consensus classification of posterior cortical atrophy

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    INTRODUCTION: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. METHODS: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. RESULTS: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. DISCUSSION: There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work
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