A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation

Tissue-remodeling processes are largely mediated by members of the matrix metalloproteinase (MMP) family of endopeptidases whose expression is strictly controlled both spatially and temporally. In this article, we have examined the molecular mechanisms that could contribute to modulate the expression of MMPs like collagenase-3 and MT1-MMP during bone formation. We have found that all-trans retinoic acid (RA), which usually downregulates MMPs, strongly induces collagenase-3 expression in cultures of embryonic metatarsal cartilage rudiments and in chondrocytic cells. This effect is dose and time dependent, requires the de novo synthesis of proteins, and is mediated by RAR-RXR heterodimers. Analysis of the signal transduction mechanisms underlying the upregulating effect of RA on collagenase-3 expression demonstrated that this factor acts through a signaling pathway involving p38 mitogen-activated protein kinase. RA treatment of chondrocytic cells also induces the production of MT1-MMP, a membrane-bound metalloproteinase essential for skeletal formation, which participates in a proteolytic cascade with collagenase-3. The production of these MMPs is concomitant with the development of an RA-induced differentiation program characterized by formation of a mineralized bone matrix, downregulation of chondrocyte markers like type II collagen, and upregulation of osteoblastic markers such as osteocalcin. These effects are attenuated in metatarsal rudiments in which RA induces the invasion of perichondrial osteogenic cells from the perichondrium into the cartilage rudiment. RA treatment also resulted in the upregulation of Cbfa1, a transcription factor responsible for collagenase-3 and osteocalcin induction in osteoblastic cells. The dynamics of Cbfa1, MMPs, and osteocalcin expression is consistent with the fact that these genes could be part of a regulatory cascade initiated by RA and leading to the induction of Cbfa1, which in turn would upregulate the expression of some of their target genes like collagenase-3 and osteocalcin

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

Search for resonances in the mass distribution of jet pairs with one or two jets identified as b-jets in proton–proton collisions at √s=13TeV with the ATLAS detector

Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identi-fied as b-jets are performed using an integrated luminosity of 3.2fb−1of proton–proton collisions with a centre-of-mass energy of √s=13TeVrecorded by the ATLAS detector at the Large Hadron Collider. Noevidence of anomalous phenomena is observed in the data, which are used to exclude, at 95%credibility level, excited b∗quarks with masses from 1.1TeVto 2.1TeVand leptophobic Z bosons with masses from 1.1TeVto 1.5TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001pb are also excluded in the mass range 1.5–5.0TeV

Measurement of the double-differential high-mass Drell-Yan cross section in pp collisions at √s = 8 TeV with the ATLAS detector

This paper presents a measurement of the double-differential cross section for the Drell-Yan Z/γ∗ → ℓ+ℓ− and photon-induced γγ → ℓ+ℓ− processes where ℓ is an electron or muon. The measurement is performed for invariant masses of the lepton pairs, mℓℓ, between 116 GeV and 1500 GeV using a sample of 20.3 fb−1 of pp collisions data at centre-of-mass energy of √s = 8 TeV collected by the ATLAS detector at the LHC in 2012. The data are presented double differentially in invariant mass and absolute dilepton rapidity as well as in invariant mass and absolute pseudorapidity separation of the lepton pair. The single-differential cross section as a function of mℓℓ is also reported. The electron and muon channel measurements are combined and a total experimental precision of better than 1% is achieved at low mℓℓ. A comparison to next-to-next-to-leading order perturbative QCD predictions using several recent parton distribution functions and including next-to-leading order electroweak effects indicates the potential of the data to constrain parton distribution functions. In particular, a large impact of the data on the photon PDF is demonstrated

Measurement of W± and Z-boson production cross sections in pp collisions at √s=13 TeV with the ATLAS detector

See paper for full list of authors - 17 pages plus author list + cover pages (34 pages total), 5 figures, 3 tables, submitted to Phys. Lett. B, All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2015-03/International audienceMeasurements of the $W^{\pm} \rightarrow \ell^{\pm} \nu$ and $Z \rightarrow \ell^+ \ell^-$ production cross sections (where $\ell^{\pm}=e^{\pm},\mu^{\pm}$) in proton-proton collisions at $\sqrt{s}=13$ TeV are presented using data recorded by the ATLAS experiment at the Large Hadron Collider, corresponding to a total integrated luminosity of 81 pb$^{-1}$. The total inclusive $W^{\pm}$-boson production cross sections times the single-lepton-flavour branching ratios are $\sigma_{W^+}^{tot}= 11.78 \pm 0.02 (stat) \pm 0.32 (sys) \pm 0.59 (lumi)$ nb and $\sigma_{W^-}^{tot} = 8.75 \pm 0.02 (stat) \pm 0.24 (sys) \pm 0.44 (lumi)$ nb for $W^+$ and $W^-$, respectively. The total inclusive $Z$-boson production cross section times leptonic branching ratio, within the invariant mass window $66 < m_{\ell\ell} < 116$ GeV, is $\sigma_{Z}^{tot} = 1.97 \pm 0.01 (stat) \pm 0.04 (sys) \pm 0.10 (lumi)$ nb. The $W^+$, $W^-$, and $Z$-boson production cross sections and cross-section ratios within a fiducial region defined by the detector acceptance are also measured. The cross-section ratios benefit from significant cancellation of experimental uncertainties, resulting in $\sigma_{W^+}^{fid}/\sigma_{W^-}^{fid} = 1.295 \pm 0.003 (stat) \pm 0.010 (sys)$ and $\sigma_{W^{\pm}}^{fid}/\sigma_{Z}^{fid} = 10.31 \pm 0.04 (stat) \pm 0.20 (sys)$. Theoretical predictions, based on calculations accurate to next-to-next-to-leading order for quantum chromodynamics and next-to-leading order for electroweak processes and which employ different parton distribution function sets, are compared to these measurements