Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta-analysis.

INTRODUCTION: To explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome. MATERIAL AND METHODS: Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks in fetuses with compared to those without a small thymus on ultrasound. SECONDARY OUTCOMES: occurrence of chorioamnionitis, intra-uterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and pre-eclampsia. RESULTS: Twelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes (PPROM) or with preterm labour with a small fetal thymus were at higher risk of preterm birth <37 (p= 0.01), <34 (12.5 (p<0.001) weeks in fetuses with compared to those without small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p<0.001). Fetuses with small thymus were not at higher risk of intra-uterine growth restriction (p= 0.3). A small thymus increased the risk of neonatal sepsis (p= 0.007) and morbidity (p= 0.003), but not the risk of pre-eclampsia (p= 0.9). CONCLUSIONS: A small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intra-uterine growth restriction and pre-eclampsia. This article is protected by copyright. All rights reserved

P62dok, a Negative Regulator of Ras and Mitogen-Activated Protein Kinase (Mapk) Activity, Opposes Leukemogenesis by P210bcr-abl

p62dok has been identified as a substrate of many oncogenic tyrosine kinases such as the chronic myelogenous leukemia (CML) chimeric p210bcr-abl oncoprotein. It is also phosphorylated upon activation of many receptors and cytoplamic tyrosine kinases. However, the biological functions of p62dok in normal cell signaling as well as in p210bcr-abl leukemogenesis are as yet not fully understood. Here we show, in hemopoietic and nonhemopoietic cells derived from p62dok−/− mice, that the loss of p62dok results in increased cell proliferation upon growth factor treatment. Moreover, Ras and mitogen-activated protein kinase (MAPK) activation is markedly sustained in p62dok−/− cells after the removal of growth factor. However, p62dok inactivation does not affect DNA damage and growth factor deprivation–induced apoptosis. Furthermore, p62dok inactivation causes a significant shortening in the latency of the fatal myeloproliferative disease induced by retroviral-mediated transduction of p210bcr-abl in bone marrow cells. These data indicate that p62dok acts as a negative regulator of growth factor–induced cell proliferation, at least in part through downregulating Ras/MAPK signaling pathway, and that p62dok can oppose leukemogenesis by p210bcr-abl

Molecular mechanisms of extracellular adenine nucleotides-mediated inhibition of human Cd4+ T lymphocytes activation

We have previously reported that ATPγS, a slowly hydrolyzed analog of ATP, inhibits the activation of human CD4+ T lymphocytes by anti-CD3 and anti-CD28 mAb. In this report we have partially characterized the signaling mechanisms involved in this immunosuppressive effect. ATPγS had no inhibitory effect on CD4+ T-cell activation induced by PMA and anti-CD28, indicating that it acts proximally to the TCR. It had no effect on the calcium rise induced by CD3/CD28 stimulation, but inhibited the phosphorylation of three kinases, ERK2, p38 MAPK and PKB, that play a key role in the activation of T cells. The receptor involved in these actions remains unidentified

Biased Saccadic Responses to Emotional Stimuli in Anxiety: An Antisaccade Study.

Research suggests that anxiety is maintained by an attentional bias to threat, and a growing base of evidence suggests that anxiety may additionally be associated with the deficient attentional processing of positive stimuli. The present study sought to examine whether such anxiety-linked attentional biases were associated with either stimulus driven or attentional control mechanisms of attentional selectivity. High and low trait anxious participants completed an emotional variant of an antisaccade task, in which they were required to prosaccade towards, or antisaccade away from a positive, neutral or threat stimulus, while eye movements were recorded. While low anxious participants were found to be slower to saccade in response to positive stimuli, irrespectively of whether a pro- or antisaccade was required, such a bias was absent in high anxious individuals. Analysis of erroneous antisaccades further revealed at trend level, that anxiety was associated with reduced peak velocity in response to threat. The findings suggest that anxiety is associated with the aberrant processing of positive stimuli, and greater compensatory efforts in the inhibition of threat. The findings further highlight the relevance of considering saccade peak velocity in the assessment of anxiety-linked attentional processing

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Induction and transmission of oncogene-induced senescence

Senescence is a cellular stress response triggered by diverse stressors, including oncogene activation, where it serves as a bona-fide tumour suppressor mechanism. Senescence can be transmitted to neighbouring cells, known as paracrine secondary senescence. Secondary senescence was initially described as a paracrine mechanism, but recent evidence suggests a more complex scenario involving juxtacrine communication between cells. In addition, single-cell studies described differences between primary and secondary senescent end-points, which have thus far not been considered functionally distinct. Here we discuss emerging concepts in senescence transmission and heterogeneity in primary and secondary senescence on a cellular and organ level