108 research outputs found
Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis.
Cryptosporidium parvum is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium, and its associated microbiota. This led us to hypothesise that specific features of the early life microbiome could predict calf susceptibility to C. parvum infection. In this study, a single faecal swab sample was collected from each calf within the first week of life in a cohort of 346 animals. All 346 calves were subsequently monitored for clinical signs of cryptosporidiosis, and calves that developed diarrhoea were tested for Rotavirus, Coronavirus, E. coli F5 (K99) and C. parvum by lateral flow test (LFT). A retrospective caseâcontrol approach was taken whereby a subset of healthy calves (Control group; n = 33) and calves that went on to develop clinical signs of infectious diarrhoea and test positive for C. parvum infection via LFT (Cryptosporidium-positive group; n = 32) were selected from this cohort, five of which were excluded due to low DNA quality. A metagenomic analysis was conducted on the faecal microbiomes of the control group (n = 30) and the Cryptosporidium-positive group (n = 30) prior to infection, to determine features predictive of cryptosporidiosis. Taxonomic analysis showed no significant differences in alpha diversity, beta diversity, and taxa relative abundance between controls and Cryptosporidium-positive groups. Analysis of functional potential showed pathways related to isoprenoid precursor, haem and purine biosynthesis were significantly higher in abundance in calves that later tested positive for C. parvum (q †0.25). These pathways are either absent or streamlined in the C. parvum parasites. Though the de novo production of isoprenoid precursors, haem and purines are absent, C. parvum has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that C. parvum may scavenge those products from an external source. The host has previously been put forward as the source of essential metabolites, but our study suggests that C. parvum may also be able to harness specific metabolic pathways of the microbiota in order to survive and replicate. This finding is important as components of these microbial pathways could be exploited as potential therapeutic targets for the prevention or mitigation of cryptosporidiosis in bovine neonates
Ab initio calculation of the neutron-proton mass difference
The existence and stability of atoms rely on the fact that neutrons are more
massive than protons. The measured mass difference is only 0.14\% of the
average of the two masses. A slightly smaller or larger value would have led to
a dramatically different universe. Here, we show that this difference results
from the competition between electromagnetic and mass isospin breaking effects.
We performed lattice quantum-chromodynamics and quantum-electrodynamics
computations with four nondegenerate Wilson fermion flavors and computed the
neutron-proton mass-splitting with an accuracy of kilo-electron volts,
which is greater than by standard deviations. We also determine the
splittings in the , , and isospin multiplets,
exceeding in some cases the precision of experimental measurements.Comment: 57 pages, 15 figures, 6 tables, revised versio
The lid domain is important, but not essential, for catalysis of Escherichia coli pyruvate kinase
Pyruvate kinase catalyses the final step of the glycolytic pathway in central energy metabolism. The monomeric structure comprises three domains: a catalytic TIM-barrel, a regulatory domain involved in allosteric activation, and a lid domain that encloses the substrates. The lid domain is thought to close over the TIM-barrel domain forming contacts with the substrates to promote catalysis and may be involved in stabilising the activated state when the allosteric activator is bound. However, it remains unknown whether the lid domain is essential for pyruvate kinase catalytic or regulatory function. To address this, we removed the lid domain of Escherichia coli pyruvate kinase type 1 (PKTIM+Reg) using protein engineering. Biochemical analyses demonstrate that, despite the absence of key catalytic residues in the lid domain, PKTIM+Reg retains a low level of catalytic activity and has a reduced binding affinity for the substrate phosphoenolpyruvate. The enzyme retains allosteric activation, but the regulatory profile of the enzyme is changed relative to the wild-type enzyme. Analytical ultracentrifugation and small-angle X-ray scattering data show that, beyond the loss of the lid domain, the PKTIM+Reg structure is not significantly altered and is consistent with the wild-type tetramer that is assembled through interactions at the TIM and regulatory domains. Our results highlight the contribution of the lid domain for facilitating pyruvate kinase catalysis and regulation, which could aid in the development of small molecule inhibitors for pyruvate kinase and related lid-regulated enzymes
Model-independent search for CP violation in D0âKâK+ÏâÏ+ and D0âÏâÏ+Ï+Ïâ decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states KâK+ÏâÏ+ and ÏâÏ+Ï+Ïâ is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fbâ1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the KâK+ÏâÏ+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the ÏâÏ+Ï+Ïâ final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Search for the lepton-flavor-violating decays Bs0âe±Όâ and B0âe±Όâ
A search for the lepton-flavor-violating decays Bs0âe±Όâ and B0âe±Όâ is performed with a data sample, corresponding to an integrated luminosity of 1.0ââfb-1 of pp collisions at âs=7ââTeV, collected by the LHCb experiment. The observed number of Bs0âe±Όâ and B0âe±Όâ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0âe±Όâ)101ââTeV/c2 and MLQ(B0âe±Όâ)>126ââTeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) and the direct CP asymmetry in B0 -> K*0 gamma
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 phi gamma has been measured using an integrated luminosity of 1.0 fb-1
of pp collision data collected by the LHCb experiment at a centre-of-mass
energy of sqrt(s)=7 TeV. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 ->
phi gamma) = 1.23 +/- 0.06(stat.) +/- 0.04(syst.) +/- 0.10(fs/fd), where the
first uncertainty is statistical, the second is the experimental systematic
uncertainty and the third is associated with the ratio of fragmentation
fractions fs/fd. Using the world average value for BR(B0 -> K*0 gamma), the
branching fraction BR(Bs0 -> phi gamma) is measured to be (3.5 +/- 0.4) x
10^{-5}.
The direct CP asymmetry in B0 -> K*0 gamma decays has also been measured with
the same data and found to be A(CP)(B0 -> K*0 gamma) = (0.8 +/- 1.7(stat.) +/-
0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the
previous experimental results and theoretical expectations.Comment: 21 pages, 3 figues, 4 table
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