150 research outputs found
Faecal neutrophil elastase-antiprotease balance reflects colitis severity
Given the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease (IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis
The -dependence of the generalised Gerasimov-Drell-Hearn integral for the deuteron, proton and neutron
The Gerasimov-Drell-Hearn (GDH) sum rule connects the anomalous contribution
to the magnetic moment of the target nucleus with an energy-weighted integral
of the difference of the helicity-dependent photoabsorption cross sections. The
data collected by HERMES with a deuterium target are presented together with a
re-analysis of previous measurements on the proton. This provides a measurement
of the generalised GDH integral covering simultaneously the nucleon-resonance
and the deep inelastic scattering regions. The contribution of the
nucleon-resonance region is seen to decrease rapidly with increasing . The
DIS contribution is sizeable over the full measured range, even down to the
lowest measured . As expected, at higher the data are found to be in
agreement with previous measurements of the first moment of . From data on
the deuteron and proton, the GDH integral for the neutron has been derived and
the proton--neutron difference evaluated. This difference is found to satisfy
the fundamental Bjorken sum rule at GeV.Comment: 12 pages, 10 figure
Single-spin Azimuthal Asymmetries in Electroproduction of Neutral Pions in Semi-inclusive Deep-inelastic Scattering
A single-spin asymmetry in the azimuthal distribution of neutral pions
relative to the lepton scattering plane has been measured for the first time in
deep-inelastic scattering of positrons off longitudinally polarized protons.
The analysing power in the sin(phi) moment of the cross section is 0.019 +/-
0.007(stat.) +/- 0.003(syst.). This result is compared to single-spin
asymmetries for charged pion production measured in the same kinematic range.
The pi^0 asymmetry is of the same size as the pi^+ asymmetry and shows a
similar dependence on the relevant kinematic variables. The asymmetry is
described by a phenomenological calculation based on a fragmentation function
that represents sensitivity to the transverse polarization of the struck quark.Comment: 4 pages, 1 figure, replaced to correct eprint author field, 2nd
replacement to correct figure; upper limit of model predictions are
corrected. No correction to data or conclusion
Evidence for Quark-Hadron Duality in the Proton Spin Asymmetry
Spin-dependent lepton-nucleon scattering data have been used to investigate
the validity of the concept of quark-hadron duality for the spin asymmetry
. Longitudinally polarised positrons were scattered off a longitudinally
polarised hydrogen target for values of between 1.2 and 12 GeV and
values of between 1 and 4 GeV. The average double-spin asymmetry in
the nucleon resonance region is found to agree with that measured in
deep-inelastic scattering at the same values of the Bjorken scaling variable
. This finding implies that the description of in terms of quark
degrees of freedom is valid also in the nucleon resonance region for values of
above 1.6 GeV.Comment: 5 pages, 1 eps figure, table added, new references added, in print in
Phys. Rev. Let
Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering
Evidence for a positive longitudinal double-spin asymmetry = 0.24
+-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive
rho^0(770) vector meson production in polarised lepton-proton scattering was
observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA
positron beam was scattered off a longitudinally polarised pure hydrogen gas
target. The average invariant mass of the photon-proton system has a value of
= 4.9 GeV, while the average negative squared four-momentum of the virtual
photon is = 1.7 GeV^2. The ratio of the present result to the
corresponding spin asymmetry in inclusive deep-inelastic scattering is in
agreement with an early theoretical prediction based on the generalised vector
meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe
Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies
Measurements of the cross section for exclusive virtual-photoproduction of
rho^0 mesons from hydrogen are reported. The data were collected by the HERMES
experiment using 27.5 GeV positrons incident on a hydrogen gas target in the
HERA storage ring. The invariant mass W of the photon-nucleon system ranges
from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the
virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with
most of the previous data at W > 4 GeV are well described by a model that
infers the W-dependence of the cross section from the dependence on the Bjorken
scaling variable x of the unpolarized structure function for deep-inelastic
scattering. In addition, a model calculation based on Off-Forward Parton
Distributions gives a fairly good account of the longitudinal component of the
rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class.
Revisions: curves added to Fig. 1, several clarifications added to tex
Sensitive Spectroscopic Detection of Large and Denatured Protein Aggregates in Solution by Use of the Fluorescent Dye Nile Red
The fluorescent dye Nile red was used as a probe for the sensitive detection of large, denatured aggregates of the model protein β-galactosidase (E. coli) in solution. Aggregates were formed by irreversible heat denaturation of β-galactosidase below and above the protein’s unfolding temperature of 57.4°C, and the presence of aggregates in heated solutions was confirmed by static light scattering. Interaction of Nile red with β-galactosidase aggregates led to a shift of the emission maximum (λmax) from 660 to 611 nm, and to an increase of fluorescence intensity. Time-resolved fluorescence and fluorescence correlation spectroscopy (FCS) measurements showed that Nile red detected large aggregates with hydrodynamic radii around 130 nm. By steady-state fluorescence measurements, it was possible to detect 1 nM of denatured and aggregated β-galactosidase in solution. The comparison with size exclusion chromatography (SEC) showed that native β-galactosidase and small aggregates thereof had no substantial effect on the fluorescence of Nile red. Large aggregates were not detected by SEC, because they were excluded from the column. The results with β-galactosidase demonstrate the potential of Nile red for developing complementary analytical methods that overcome the size limitations of SEC, and can detect the formation of large protein aggregates at early stages
Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum
Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control
Common Peptides Study of Aminoacyl-tRNA Synthetases
Aminoacyl tRNA synthetases (aaRSs) constitute an essential enzyme super-family, providing fidelity of the translation process of mRNA to proteins in living cells. They are common to all kingdoms and are of utmost importance to all organisms. It is thus of great interest to understand the evolutionary relationships among them and underline signature motifs defining their common domains.We utilized the Common Peptides (CPs) framework, based on extracted deterministic motifs from all aaRSs, to study family-specific properties. We identified novel aaRS–class related signatures that may supplement the current classification methods and provide a basis for identifying functional regions specific to each aaRS class. We exploited the space spanned by the CPs in order to identify similarities between aaRS families that are not observed using sequence alignment methods, identifying different inter-aaRS associations across different kingdom of life. We explored the evolutionary history of the aaRS families and evolutionary origins of the mitochondrial aaRSs. Lastly, we showed that prevalent CPs significantly overlap known catalytic and binding sites, suggesting that they have meaningful functional roles, as well as identifying a motif shared between aaRSs and a the Biotin-[acetyl-CoA carboxylase] synthetase (birA) enzyme overlapping binding sites in both families.The study presents the multitude of ways to exploit the CP framework in order to extract meaningful patterns from the aaRS super-family. Specific CPs, discovered in this study, may play important roles in the functionality of these enzymes. We explored the evolutionary patterns in each aaRS family and tracked remote evolutionary links between these families
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