1,111 research outputs found
Connective tissue presentation in two families expands the phenotypic spectrum of PYROXD1 disorders
Recessive variants in the oxidoreductase PYROXD1 are reported to cause a myopathy in 22 affected individuals from 15 families. Here, we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction. Proband AII:1 is compound heterozygous for the recurrent PYROXD1 variant Chr12(GRCh38):g.21452130A\u3eG;NM_024854.5:c.464A\u3eG;p.(N155S) and Chr12(GRCh38):g.21462019_21462022del;NM_024854.5:c.892_895del;p.(V298Mfs*4) and proband BII:1 is compound heterozygous for Chr12(GRCh38):g.21468739-21468741del;NM_024854.5:c.1488_1490del;p.(E496del) and Chr12(GRCh38):g.21467619del;NM_024854.5:c.1254+1del. RNA studies demonstrate c.892_895del;p.(V298Mfs*4) is targeted by nonsense mediated decay and c.1254+1delG elicits in-frame skipping of exon-11. Western blot from cultured fibroblasts shows reduced PYROXD1 protein levels in both probands. Testing urine from BII:1 and six individuals with PYROXD1 myopathy showed elevated levels of deoxypyridinoline, a mature collagen crosslink, correlating with PYROXD1-disorder severity. Urine and serum amino acid testing of the same individuals revealed no reportable changes. In contrast to PYROXD1 knock-out, we find no evidence for disrupted tRNA ligase activity, as measured via XBP1 splicing, in fibroblasts expressing PYROXD1 variants. In summary, we expand the clinical spectrum of PYROXD1-related disorders to include an overlapping connective tissue and myopathy presentation, identify three novel, pathogenic PYROXD1 variants, and provide preliminary evidence that elevated urine DPD crosslinks may provide a clinical biomarker for PYROXD1 disorders. Our results advocate consideration of PYROXD1 variants in the differential diagnosis for undiagnosed individuals presenting with a connective tissue disorder and myopathy
Opportunities for mobilizing recalcitrant phosphorus from agricultural soils: a review
Background : Phosphorus (P) fertilizer is usually applied
in excess of plant requirement and accumulates in soils
due to its strong adsorption, rapid precipitation and
immobilisation into unavailable forms including organic
moieties. As soils are complex and diverse chemical,
biochemical and biological systems, strategies to access
recalcitrant soil P are often inefficient, case specific and
inconsistently applicable in different soils. Finding a
near-universal or at least widely applicable solution to
the inefficiency in agricultural P use by plants is an
important unsolved problem that has been under investigation
for more than half a century.
Scope : In this paper we critically review the strategies
proposed for the remobilization of recalcitrant soil phosphorus for crops and pastures worldwide. We have
additionally performed a meta-analysis of available soil
31P–NMR data to establish the potential agronomic
value of different stored P forms in agricultural soils.
Conclusions : Soil inorganic P stocks accounted on average
for 1006 ± 115 kg ha−1 (57 ± 7%), while the
monoester P pool accounted for 587 ± 32 kg ha−1
(33 ± 2%), indicating the huge potential for the future
agronomic use of the soil legacy P. New impact driven
research is needed in order to create solutions for the
sustainable management of soil P stocks
A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer
Background
In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage.
Methods
Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case.
Results
We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the "Reverse Warburg effect" in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor clinical outcome, namely pT3 stage of the tumour.
Conclusions
In summary, this work demonstrates for the first time the clinico-pathological significance of the lactate shuttle in prostate cancer. It also suggests that other alterations in CAFs may be useful prognostic factors, and further supports the use of MCT1/MCT4 as targets for PCa therapy.NPG received a fellowship from the Portuguese Foundation for Science and Technology (FCT), refs. SFRH/BD/61027/2009. This work was supported by the FCT grant ref. PTDC/SAUMET/113415/2009, under the scope of "Programa Operacional Tematico Factores de Competitividade" (COMPETE) of "Quadro Comunitario de Apoio III" and co-financed by Fundo Comunitario Europeu FEDER. JA was supported by a Boehringer Ingelheim Fonds fellowship
Precise measurement of the top quark mass in the dilepton channel at D0
We measure the top quark mass (mt) in ppbar collisions at a center of mass
energy of 1.96 TeV using dilepton ttbar->W+bW-bbar->l+nubl-nubarbbar events,
where l denotes an electron, a muon, or a tau that decays leptonically. The
data correspond to an integrated luminosity of 5.4 fb-1 collected with the D0
detector at the Fermilab Tevatron Collider. We obtain mt = 174.0 +- 1.8(stat)
+- 2.4(syst) GeV, which is in agreement with the current world average mt =
173.3 +- 1.1 GeV. This is currently the most precise measurement of mt in the
dilepton channel.Comment: 7 pages, 4 figure
Journal Staff
We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar < 1.0 and transverse momenta 30 < p(T)(gamma) < 200 GeV. The b-quark jets are required to have p(T)(jet) > 15 GeVand vertical bar y(jet)vertical bar < 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators
A search for charged massive long-lived particles
We report on a search for charged massive long-lived particles (CMLLPs),
based on 5.2 fb of integrated luminosity collected with the D0 detector
at the Fermilab Tevatron collider. We search for events in which one
or more particles are reconstructed as muons but have speed and ionization
energy loss inconsistent with muons produced in beam collisions.
CMLLPs are predicted in several theories of physics beyond the standard model.
We exclude pair-produced long-lived gaugino-like charginos below 267 GeV and
higgsino-like charginos below 217 GeV at 95% C.L., as well as long-lived scalar
top quarks with mass below 285 GeV.Comment: submitted to Phys. Rev. Letter
Search for single vector-like quarks in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for hypothetical vector-like quarks in ppbar collisions
at sqrt(s) = 1.96 TeV. The data were collected by the D0 detector at the
Fermilab Tevatron Collider and correspond to an integrated luminosity of 5.4
fb^(-1). We select events with a final state composed of a W or Z boson and a
jet consistent with a heavy object decay. We observe no significant excess in
comparison to the background prediction and set limits on production cross
sections for vector-like quarks decaying to W+jet and Z+jet. These are the most
stringent mass limits for electroweak single vector-like quark production at
hadron colliders.Comment: submitted to Phys. Rev. Let
Measurement of the top quark pair production cross section in the lepton+jets channel in proton-antiproton collisions at =1.96 TeV
We present a measurement of the inclusive top quark pair production cross
section in \ppbar collisions at (\sqrt{s}=1.96) TeV utilizing data
corresponding to an integrated luminosity of \lumi\ collected with the D0
detector at the Fermilab Tevatron Collider. We consider final states containing
one high- isolated electron or muon and at least two jets, and we
perform three analyses: one exploiting specific kinematic features of \ttbar
events, the second using -jet identification, and the third using both
techniques to separate \ttbar\ signal from background. In the third case, we
determine simultaneously the cross section and the ratio of the
production rates of +heavy flavor jets and +light flavor jets, which
reduces the impact of the systematic uncertainties related to the background
estimation. Assuming a top quark mass of 172.5 GeV, we obtain
pb. This result agrees with
predictions of the standard model.Comment: 19 pages, 6 figures, submitted to Phys. Rev.
Direct measurement of the mass difference between top and antitop quarks
We present a direct measurement of the mass difference between top and
antitop quarks (dm) in lepton+jets top-antitop final states using the "matrix
element" method. The purity of the lepton+jets sample is enhanced for
top-antitop events by identifying at least one of the jet as originating from a
b quark. The analyzed data correspond to 3.6 fb-1 of proton-antiproton
collisions at 1.96 TeV acquired by D0 in Run II of the Fermilab Tevatron
Collider. The combination of the e+jets and mu+jets channels yields dm = 0.8
+/- 1.8 (stat) +/- 0.5 (syst) GeV, which is in agreement with the standard
model expectation of no mass difference.Comment: submitted to Phys. Rev.
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