225 research outputs found
Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism
BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations
Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22-23 March 2017.
Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual's abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide
Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II
Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminusâlipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation
Observation of an Exotic Baryon in Exclusive Photoproduction from the Deuteron
In an exclusive measurement of the reaction , a
narrow peak that can be attributed to an exotic baryon with strangeness
is seen in the invariant mass spectrum. The peak is at
GeV/c with a measured width of 0.021 GeV/c FWHM, which is largely
determined by experimental mass resolution. The statistical significance of the
peak is . The mass and width of the observed peak are
consistent with recent reports of a narrow baryon by other experimental
groups.Comment: 5 pages, 5 figure
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n
We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic
range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c)
peaks where two nucleons each have 20% or less, and the third nucleon has most
of the transferred energy. These fast pp and pn pairs are back-to-back with
little momentum along the three-momentum transfer, indicating that they are
spectators. Experimental and theoretical evidence indicates that we have
measured distorted two-nucleon momentum distributions by striking the third
nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR
Search for the pentaquark in the reaction
A search for the \thp in the reaction was completed
using the CLAS detector at Jefferson Lab. A study of the same reaction,
published earlier, reported the observation of a narrow \thp resonance. The
present experiment, with more than 30 times the integrated luminosity of our
earlier measurement, does not show any evidence for a narrow pentaquark
resonance. The angle-integrated upper limit on \thp production in the mass
range of 1.52 to 1.56 GeV/c for the reaction is
0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and
angular distribution of \thp production. Using \lamstar production as an
empirical measure of rescattering in the deuteron, the cross section upper
limit for the elementary reaction is estimated to be
a factor of 10 higher, {\it i.e.}, nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment
Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12
Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using
2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12
targets in the CLAS detector. A_LT' is related to the imaginary part of the
longitudinal-transverse interference and in quasifree nucleon knockout it
provides an unambiguous signature for final state interactions (FSI).
Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3%
for data with good statistical precision. Optical Model in Eikonal
Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation
(RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure
Onset of asymptotic scaling in deuteron photodisintegration
We investigate the transition from the nucleon-meson to quark-gluon
description of the strong interaction using the photon energy dependence of the
differential cross section for photon energies above 0.5 GeV and
center-of-mass proton angles between and . A possible
signature for this transition is the onset of cross section scaling
with the total energy squared, , at some proton transverse momentum, .
The results show that the scaling has been reached for proton transverse
momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime
is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure
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