207 research outputs found
Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia
Pharmacological, genetic and expression studies implicate N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia (SCZ). Similarly, several lines of evidence suggest that autism spectrum disorders (ASD) could be due to an imbalance between excitatory and inhibitory neurotransmission. As part of a project aimed at exploring rare and/or de novo mutations in neurodevelopmental disorders, we have sequenced the seven genes encoding for NMDA receptor subunits (NMDARs) in a large cohort of individuals affected with SCZ or ASD (n=429 and 428, respectively), parents of these subjects and controls (n=568). Here, we identified two de novo mutations in patients with sporadic SCZ in GRIN2A and one de novo mutation in GRIN2B in a patient with ASD. Truncating mutations in GRIN2C, GRIN3A and GRIN3B were identified in both subjects and controls, but no truncating mutations were found in the GRIN1, GRIN2A, GRIN2B and GRIN2D genes, both in patients and controls, suggesting that these subunits are critical for neurodevelopment. The present results support the hypothesis that rare de novo mutations in GRIN2A or GRIN2B can be associated with cases of sporadic SCZ or ASD, just as it has recently been described for the related neurodevelopmental disease intellectual disability. The influence of genetic variants appears different, depending on NMDAR subunits. Functional compensation could occur to counteract the loss of one allele in GRIN2C and GRIN3 family genes, whereas GRIN1, GRIN2A, GRIN2B and GRIN2D appear instrumental to normal brain development and function
Genetic characterization of morphologically variant strains of Paracoccidioides brasiliensis
Molecular characterization of Paracoccidioides brasiliensis variant strains that had been preserved under mineral oil for decades was carried out by random amplified polymorphic DNA analysis (RAPD). On P. brasiliensis variants in the transitional phase and strains with typical morphology, RAPD produced reproducible polymorphic amplification products that differentiated them. A dendrogram based on the generated RAPD patterns placed the 14 P. brasiliensis strains into five groups with similarity coefficients of 72%. A high correlation between the genotypic and phenotypic characteristics of the strains was observed. A 750 bp-RAPD fragment found only in the wild-type phenotype strains was cloned and sequenced. Genetic similarity analysis using BLASTx suggested that this RAPD marker represents a putative domain of a hypothetical flavin-binding monooxygenase (FMO)-like protein of Neurospora crassa.FiocruzBritish Council Progra
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV
Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of
2.76 TeV per nucleon pair was studied using data collected with the CMS
detector at the LHC. Fragmentation functions are constructed using
charged-particle tracks with transverse momenta pt > 4 GeV for dijet events
with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events
are compared to those in pp data as a function of collision centrality, as well
as dijet-pt imbalance. Special emphasis is placed on the most central PbPb
events including dijets with unbalanced momentum, indicative of energy loss of
the hard scattered parent partons. The fragmentation patterns for both the
leading and subleading jets in PbPb collisions agree with those seen in pp data
at 2.76 TeV. The results provide evidence that, despite the large parton energy
loss observed in PbPb collisions, the partition of the remaining momentum
within the jet cone into high-pt particles is not strongly modified in
comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic
Genetic characterization of morphologically variant strains of Paracoccidioides brasiliensis
Lipidomic Analysis of Extracellular Vesicles from the Pathogenic Phase of Paracoccidioides brasiliensis
Background: Fungal extracellular vesicles are able to cross the cell wall and transport molecules that help in nutrient acquisition, cell defense, and modulation of the host defense machinery.Methodology/Principal Findings: Here we present a detailed lipidomic analysis of extracellular vesicles released by Paracoccidioides brasiliensis at the yeast pathogenic phase. We compared data of two representative isolates, Pb3 and Pb18, which have distinct virulence profiles and phylogenetic background. Vesicle lipids were fractionated into different classes and analyzed by either electrospray ionization- or gas chromatography-mass spectrometry. We found two species of monohexosylceramide and 33 phospholipid species, including phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol. Among the phospholipid-bound fatty acids in extracellular vesicles, C181 predominated in Pb3, whereas C18:2 prevailed in Pb18. the prevalent sterol in Pb3 and Pb18 vesicles was brassicasterol, followed by ergosterol and lanosterol. Inter-isolate differences in sterol composition were observed, and also between extracellular vesicles and whole cells.Conclusions/Significance: the extensive lipidomic analysis of extracellular vesicles from two P. brasiliensis isolates will help to understand the composition of these fungal components/organelles and will hopefully be useful to study their biogenesis and role in host-pathogen interactions.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institutes of Health (NIH)Universidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USAUniversidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFAPESP: 06/05095-6FAPESP: 07/04757-8FAPESP: 07/59768-4CNPq: 301666/2010-5National Institutes of Health (NIH): 5G12RR008124-16A1National Institutes of Health (NIH): 5G12RR008124-16A1S1National Institutes of Health (NIH): G12MD007592Web of Scienc
Improper inhaler technique is associated with poor asthma control and frequent emergency department visits
Early-life predictors of resilience and related outcomes up to 66 years later in the 6-day sample of the 1947 Scottish mental survey.
PURPOSE: Psychological resilience, the ability to manage and quickly recover from stress and trauma, is associated with a range of health and wellbeing outcomes. Resilience is known to relate to personality, self-esteem and positive affect, and may also depend upon childhood experience and stress. In this study, we investigated the role of early-life contributors to resilience and related factors in later life. METHODS: We used data from the 6-day sample of the Scottish mental survey 1947, an initially representative sample of Scottish children born in 1936. They were assessed on a range of factors between the ages of 11 and 27 years, and resilience and other outcomes at 77 years. RESULTS: Higher adolescent dependability unexpectedly predicted lower resilience in older-age, as did childhood illnesses, while a count of specific stressors experienced throughout early life significantly predicted higher later-life resilience. We also observed significant cross-sectional correlations between resilience and measures of physical health, mental health, wellbeing and loneliness. Some of the associations between early-life predictors and later-life outcomes were significantly mediated by resilience. CONCLUSIONS: Our results support the hypothesis that stress throughout early life may help to build resilience in later-life, and demonstrate the importance of resilience as a mediator of other influences on health and wellbeing in older age. We suggest that the mechanisms determining how early-life stress leads to higher resilience are worthy of further investigation, and that psychological resilience should be a focus of research and a target for therapeutic interventions aiming to improve older-age health and wellbeing
Time to focus on outcome assessment tools for childhood vasculitis
Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform a validation study using the original Birmingham vasculitis activity score as well as the disease extent index to measure disease activity in childhood vasculitis. Presently, there are efforts in place to develop a pediatric vasculitis activity score. This paper reviews the current understanding about the assessment tools (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely used for evaluation of the disease activity and damage status of the children with vasculitis
Dimensional and hierarchical models of depression using the Beck Depression Inventory-II in an Arab college student sample
Abstract Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA) could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i) using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II) in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models); (ii) to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25). Method Participants (N = 624) were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM) had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All regression weights of the dimensional models were significantly different from zero (P Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably contains hierarchical and dimensional elements. The bifactor model is emerging as the best way to account for the clinical heterogeneity of depression. The psychometric characteristics of the BDI-II lend support to our CFA results.</p
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