2,301 research outputs found

    Low Dose Aerosol Fitness at the Innate Phase of Murine Infection Better Predicts Virulence amongst Clinical Strains of Mycobacterium tuberculosis

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    Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 10 4 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 10 2 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance: The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism o

    Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease

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    ABSTRACT: Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxelbased morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies

    What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

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    Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

    Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

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    The Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction is measured in a data sample corresponding to 0.41fb−1fb^{-1} of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2ÎČ\beta measurement from B0→J/ψKS0B^0\to J/\psi K_S^0 The time-integrated branching fraction is measured to be BF(Bs0→J/ψKS0)=(1.83±0.28)×10−5BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}. This is the most precise measurement to date

    Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

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    A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

    Differential branching fraction and angular analysis of the decay B0→K∗0ÎŒ+Ό−

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    The angular distribution and differential branching fraction of the decay B 0→ K ∗0 ÎŒ + ÎŒ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions

    Search for the decay Bs0→D*∓π±

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    A search for the decay Bs0→D*∓π± is presented using a data sample corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions collected by LHCb. This decay is expected to be mediated by a W-exchange diagram, with little contribution from rescattering processes, and therefore a measurement of the branching fraction will help us to understand the mechanism behind related decays such as Bs0→π+π- and Bs0→DD- . Systematic uncertainties are minimized by using B0→D*∓π± as a normalization channel. We find no evidence for a signal, and set an upper limit on the branching fraction of B(Bs0→D*∓π±)<6.1(7.8)×10-6 at 90% (95%) confidence level

    Opposite-side flavour tagging of B mesons at the LHCb experiment

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    The calibration and performance of the oppositeside flavour tagging algorithms used for the measurements of time-dependent asymmetries at the LHCb experiment are described. The algorithms have been developed using simulated events and optimized and calibrated with B + →J/ψK +, B0 →J/ψK ∗0 and B0 →D ∗− ÎŒ + ΜΌ decay modes with 0.37 fb−1 of data collected in pp collisions at √ s = 7 TeV during the 2011 physics run. The oppositeside tagging power is determined in the B + → J/ψK + channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty is statistical and the second is systematic

    Observation of excited Lambda_b0 baryons

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    Using pp collision data corresponding to 1.0 fb-1 integrated luminosity collected by the LHCb detector, two narrow states are observed in the Lambda_b0pi+pi- spectrum with masses 5911.97 +- 0.12(stat) +- 0.02(syst) +- 0.66(Lambda_b0 mass) MeV/c^2 and 5919.77 +- 0.08(stat) +- 0.02(syst) +- 0.66(Lambda_b0 mass) MeV/c^2. The significances of the observations are 5.2 and 10.2 standard deviations, respectively. These states are interpreted as the orbitally-excited Lambda_b0 baryons, Lambda_b*0(5912) and Lambda_b*0(5920).Comment: Replaced by version published in Phys. Rev. Lett, modified fit with better mass resolution treatmen
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