106 research outputs found

    Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains

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    Objectives: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTHrelated protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. Methods: We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. Results: We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H 2 O 2 )-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H 2 O 2 on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. Conclusion: These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP.This work has been funded by grants from the Fundacion para la Investigacion Osea y Metabolismo Mineral-FEIOMM and the Instituto de Salud Carlos III (PI11/00449, PI15/00340, PI1600065, RD12/0043/0029, RD12/0043/0008 and RD12/0043/0018,). J. A. Ardua, D. Lozano, and S. Portal-Nunez are recipients of postdoctoral contracts from the Ministerio de Economia y Competitividad, Juan de la Cierva program JCI-2011-09548, FPDI-2013-17268, and RETICEF [FEDER “una manera de hacer Europa” (RD12/0043/0008)

    Renal size and cardiovascular risk in prepubertal children

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    Renal size is an important parameter for the evaluation and diagnosis of kidney disease and has been associated with several cardiovascular risk factors in patients with kidney failure. These results are however discordant and studies in healthy children are lacking. We aimed to study the association between renal size (length and volume) and cardiovascular risk parameters in healthy children. Clinical, analytical and ultrasound parameters [renal length, renal volume, perirenal fat and carotid intima-media thickness (cIMT)] were determined in 515 healthy prepubertal children (176 lean, 208 overweight and 131 obese). Renal length and volume associated significantly and positively with several anthropometric and cardiovascular risk parameters including cIMT and systolic blood pressure (SBP) (all p < 0.001). Renal length and volume associated with cIMT and SBP in all study subgroups, but these associations were predominant in obese children, in whom these associations were independent after adjusting for age, gender and BSA (all p < 0.05). In multivariate analyses in the study subjects as a whole, renal length was an independent predictor of cIMT (ÎČ = 0.310, p < 0.0001) and SBP (ÎČ = 0.116, p = 0.03). Renal size associates with cIMT and SBP, independent of other well-established cardiovascular risk factors, and may represent helpful parameters for the early assessment of cardiovascular risk in children

    Search for top squark pair production in pp collisions at root s=13 TeV using single lepton events

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    Observation of Electroweak Production of Same-Sign W Boson Pairs in the Two Jet and Two Same-Sign Lepton Final State in Proton-Proton Collisions at √s=13 TeV

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    The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 35.9    fb−1 collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. The observed significance of the signal is 5.5 standard deviations, where a significance of 5.7 standard deviations is expected based on the standard model. The ratio of measured event yields to that expected from the standard model at leading order is 0.90±0.22. A cross section measurement in a fiducial region is reported. Bounds are given on the structure of quartic vector boson interactions in the framework of dimension-8 effective field theory operators and on the production of doubly charged Higgs bosons

    Measurements of properties of the Higgs boson decaying into the four-lepton final state in pp collisions at s=13 \sqrt{s}=13 TeV

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    Search for resonant and nonresonant Higgs boson pair production in the b(b)over-barl nu l nu final state in proton-proton collisions at root s=13 TeV

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    Searches for resonant and nonresonant pair-produced Higgs bosons (HH) decaying respectively into l nu l nu, through either W or Z bosons, and b (b) over bar are presented. The analyses are based on a sample of proton-proton collisions at root s = 13 TeV, collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1). Data and predictions from the standard model are in agreement within uncertainties. For the standard model HH hypothesis, the data exclude at 95% confidence level a product of the production cross section and branching fraction larger than 72 fb, corresponding to 79 times the standard model prediction. Constraints are placed on different scenarios considering anomalous couplings, which could affect the rate and kinematics of HH production. Upper limits at 95% confidence level are set on the production cross section of narrow-width spin-0 and spin-2 particles decaying to Higgs boson pairs, the latter produced with minimal gravity-like coupling.Peer reviewe

    Search for supersymmetry in events with at least three electrons or muons, jets, and missing transverse momentum in proton-proton collisions at √s=13 TeV

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    Measurements of the pp→ZZ production cross section and the Z→4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s= 13TeV

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    Bose-Einstein correlations in pp, pPb, and PbPb collisions at root s(NN)=0.9-7 TeV

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    Quantum-statistical (Bose-Einstein) two-particle correlations are measured in pp collisions at root s = 0.9, 2.76, and 7 TeV, as well as in pPb and peripheral PbPb collisions at nucleon-nucleon center-of-mass energies of 5.02 and 2.76 TeV, respectively, using the CMS detector at the Large Hadron Collider. Separate analyses are performed for same-sign unidentified charged particles as well as for same-sign pions and kaons identified via their energy loss in the silicon tracker. The characteristics of the one-, two-, and three-dimensional correlation functions are studied as functions of the pair average transverse momentum (k(T)) and the charged-particle multiplicity in the event. For all systems, the extracted correlation radii steadily increase with the event multiplicity, and decrease with increasing k(T). The radii are in the range 1-5 fm, the largest values corresponding to very high multiplicity pPb interactions and to peripheral PbPb collisions with multiplicities similar to those seen in pPb data. It is also observed that the dependencies of the radii on multiplicity and k(T) largely factorize. At the same multiplicity, the radii are relatively independent of the colliding system and center-of-mass energy.Peer reviewe

    Search for resonant and nonresonant Higgs boson pair production in the bbÂŻâ„“Îœâ„“Îœ final state in proton-proton collisions at √s=13 TeV

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    Searches for resonant and nonresonant pair-produced Higgs bosons (HH) decaying respectively into ℓΜℓΜ, through either W or Z bosons, and bb ÂŻ ÂŻ ÂŻ bbÂŻ are presented. The analyses are based on a sample of proton-proton collisions at s √ =13 s=13 TeV, collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb−1. Data and predictions from the standard model are in agreement within uncertainties. For the standard model HH hypothesis, the data exclude at 95% confidence level a product of the production cross section and branching fraction larger than 72 fb, corresponding to 79 times the standard model prediction. Constraints are placed on different scenarios considering anomalous couplings, which could affect the rate and kinematics of HH production. Upper limits at 95% confidence level are set on the production cross section of narrow-width spin-0 and spin-2 particles decaying to Higgs boson pairs, the latter produced with minimal gravity-like coupling
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