Pets as Sentinels of Human Exposure to Neurotoxic Metals

The idea that animals may be used as sentinels of environmental hazards pending over humans and the associated public health implications is not a new one. Nowadays pets are being used as bioindicators for the effects of environmental contaminants in human populations. This is of paramount importance due to the large increase in the worldwide distribution of synthetic chemicals, particularly in the built environment. Companion animals share the habitat with humans being simultaneously exposed to and suffering the same disease spectrum as their masters. Moreover, their shorter latency periods (due to briefer lifespans) enable them to act as early warning systems, allowing timely public health interventions. The rise on ethical constraints on the use of animals and, consequently, on the sampling they can be subjected to has led to the preferential use of noninvasive matrices, and in this case we are looking into hair. This chapter focuses in three non-essential metals: mercury, lead, and cadmium, due to their ubiquitous presence in the built environment and their ability of affecting the mammal nervous system. There is a fairly short amount of studies reporting the concentrations of these metals in pets’ hair, particularly for cats. These studies are characterized, and the metal concentrations corresponding to different parameters (e.g., age, sex, diet, rearing) are described in order to provide the reader with a general vision on the use of this noninvasive matrix on the studies conducted since the last two decades of the twentieth century.publishe

Blimp1 Activation by AP-1 in Human Lung Cancer Cells Promotes a Migratory Phenotype and Is Inhibited by the Lysyl Oxidase Propeptide

B lymphocyte-induced maturation protein 1 (Blimp1) is a master regulator of B cell differentiation, and controls migration of primordial germ cells. Recently we observed aberrant Blimp1 expression in breast cancer cells resulting from an NF-κB RelB to Ras signaling pathway. In order to address the question of whether the unexpected expression of Blimp1 is seen in other epithelial-derived tumors, we selected lung cancers as they are frequently driven by Ras signaling. Blimp1 was detected in all five lung cancer cell lines examined and shown to promote lung cancer cell migration and invasion. Interrogation of microarray datasets demonstrated elevated BLIMP1 RNA expression in lung adenocarcinoma, pancreatic ductal carcinomas, head and neck tumors as well as in glioblastomas. Involvement of Ras and its downstream kinase c-Raf was confirmed using mutant and siRNA strategies. We next addressed the issue of mechanism of Blimp1 activation in lung cancer. Using knockdown and ectopic expression, the role of the Activator Protein (AP)-1 family of transcription factors was demonstrated. Further, chromatin immunoprecipitation assays confirmed binding to identified AP-1 elements in the BLIMP1 promoter of ectopically expressed c-Jun and of endogenous AP-1 subunits following serum stimulation. The propeptide domain of lysyl oxidase (LOX-PP) was identified as a tumor suppressor, with ability to reduce Ras signaling in lung cancer cells. LOX-PP reduced expression of Blimp1 by binding to c-Raf and inhibiting activation of AP-1, thereby attenuating the migratory phenotype of lung cancer cells. Thus, Blimp1 is a mediator of Ras/Raf/AP-1 signaling that promotes cell migration, and is repressed by LOX-PP in lung cancer

Measurement of the tt¯tt¯ production cross section in pp collisions at √s=13 TeV with the ATLAS detector

A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

Measurement of the energy asymmetry in t(t)over-barj production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using $$139\,{\mathrm {fb}}^{-1}$$ 139 fb - 1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at $$\sqrt{s}=13\,\text {TeV}$$ s = 13 TeV . The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic $$t{\bar{t}}$$ t t ¯ decay channel, and the hadronically decaying top quark must have transverse momentum above $$350\,\text {GeV}$$ 350 GeV . The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be $$-0.043\pm 0.020$$ - 0.043 ± 0.020 , in agreement with the SM prediction of $$-0.037\pm 0.003$$ - 0.037 ± 0.003 . Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits