359 research outputs found
Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model
Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n = 6) and asthmatic (n = 8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p = 0.048, 12.4 (SD 6.1), p = 0.016 and 7.3% (SD 6.6), p = 0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p = 0.02), 32.9% (SD 8.6), p = 0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target
Low-energy neutron-deuteron reactions with N3LO chiral forces
We solve three-nucleon Faddeev equations with nucleon-nucleon and
three-nucleon forces derived consistently in the framework of chiral
perturbation theory at next-to-next-to-next-to-leading order in the chiral
expansion. In this first investigation we include only matrix elements of the
three-nucleon force for partial waves with the total two-nucleon
(three-nucleon) angular momenta up to 3 (5/2). Low-energy neutron-deuteron
elastic scattering and deuteron breakup reaction are studied. Emphasis is put
on Ay puzzle in elastic scattering and cross sections in symmetric-space-star
and neutron-neutron quasi-free-scattering breakup configurations, for which
large discrepancies between data and theory have been reported.Comment: 22 pages, 7 figure
Dependence of the C(,pd) reaction on photon linear polarisation
The sensitivity of the C reaction to photon linear
polarisation has been determined at MAMI, giving the first measurement of the
reaction for a nucleus heavier than He. Photon asymmetries and cross
sections were measured for =170 to 350 MeV. For below
the resonance, reactions leaving the residual Be near its ground
state show a positive asymmetry of up to 0.3, similar to that observed for
He suggesting a similar reaction mechanism for the two nuclei.Comment: 4 pages, 2 figure
Benchmark Calculation of the Three-Nucleon Photodisintegration
A benchmark is set on the three-nucleon photodisintegration calculating the total cross section with modern realistic two- and three-nucleon forces (AV18, UrbIX) using both the Faddeev equations and the Lorentz Integral Transform method. This test shows that the precision of three-body calculations involving continuum states is considerably higher than experimental uncertainties. Effects due to retardations, higher multipoles, meson exchange currents and Coulomb force are studied
Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells
<p>Abstract</p> <p>Background</p> <p>Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs).</p> <p>Methods</p> <p>To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers.</p> <p>Results</p> <p>RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates.</p> <p>Conclusions</p> <p>The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.</p
Structure-Related Differences between Cytochrome Oxidase I Proteins in a Stable Heteroplasmic Mitochondrial System
open5siMIUR, programma SIR, progetto n. RBSI14G0P5 "MItochoNdria, Germ Line and sEx" (MINGLE)Many bivalve species have two types of mitochondrial DNA passed independently through the female line (F genome) and male line (M genome). Here we study the cytochrome oxidase I protein in such bivalve species and provide evidence for differences between the F and M proteins in amino acid property values, particularly relating to hydrophobicity and helicity. The magnitude of these differences varies between different regions of the protein and the change from the ancestor is most marked in the M protein. The observed changes occur in parallel and in the same direction in the different species studied. Two possible causes are considered, first relaxation of purifying selection with drift and second positive selection. These may operate in different ways in different regions of the protein. Many different amino acid substitutions contribute in a small way to the observed variation, but substitutions involving alanine and serine have a quantitatively large effect. Some of these substitutions are potential targets for phosphorylation and some are close to residues of functional importance in the catalytic mechanism. We propose that the observed changes in the F and M proteins might contribute to functional differences between them relating to ATP production and mitochondrial membrane potential with implications for sperm function.openSkibinski, David O F; Ghiselli, Fabrizio; Diz, Angel P; Milani, Liliana; Mullins, Jonathan G LSkibinski, David O F; Ghiselli, Fabrizio; Diz, Angel P; Milani, Liliana; Mullins, Jonathan G
Final State Interaction Effects in pol 3He(pol e,e'p)
Asymmetries in quasi-elastic pol 3He(pol e,e'p) have been measured at a
momentum transfer of 0.67 (GeV/c)^2 and are compared to a calculation which
takes into account relativistic kinematics in the final state and a
relativistic one-body current operator. With an exact solution of the Faddeev
equation for the 3He-ground state and an approximate treatment of final state
interactions in the continuum good agreement is found with the experimental
data.Comment: 11 pages, 6 figures, submitted to Phys. Lett. B, revised version,
sensitivity study to relativity and NN-potential adde
Muon capture by 3He nuclei followed by proton and deuteron production
The paper describes an experiment aimed at studying muon capture by
nuclei in pure and mixtures at various densities. Energy distributions of
protons and deuterons produced via and are measured for the
energy intervals MeV and MeV, respectively. Muon capture
rates, and are obtained using two different analysis methods. The
least--squares methods gives , . The Bayes theorem
gives ,
. The experimental
differential capture rates, and , are compared with theoretical
calculations performed using the plane--wave impulse approximation (PWIA) with
the realistic NN interaction Bonn B potential. Extrapolation to the full energy
range yields total proton and deuteron capture rates in good agreement with
former results.Comment: 17 pages, 13 figures, accepted for publication in PR
Proton-deuteron radiative capture cross sections at intermediate energies
Differential cross sections of the reaction have been
measured at deuteron laboratory energies of 110, 133 and 180 MeV. The data were
obtained with a coincidence setup measuring both the outgoing He and the
photon. The data are compared with modern calculations including all possible
meson-exchange currents and two- and three- nucleon forces in the potential.
The data clearly show a preference for one of the models, although the shape of
the angular distribution cannot be reproduced by any of the presented models.Comment: 6 pages, 6 figures, accepted for publication in EPJ
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