The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Search for the b(b)over-bar decay of the Standard Model Higgs boson in associated (W/Z)H production with the ATLAS detector

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/ licenses/by/4.0

Search for supersymmetry in events with large missing transverse momentum, jets, and at least one tau lepton in 20 fb−1 of √s= 8 TeV proton-proton collision data with the ATLAS detector

© 2014, The Author(s). A search for supersymmetry (SUSY) in events with large missing transverse momentum, jets, at least one hadronically decaying tau lepton and zero or one additional light leptons (electron/muon), has been performed using 20.3fb−1of proton-proton collision data at √ s= 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No excess above the Standard Model background expectation is observed in the various signal regions and 95% confidence level upper limits on the visible cross section for new phenomena are set. The results of the analysis are interpreted in several SUSY scenarios, significantly extending previous limits obtained in the same final states. In the framework of minimal gauge-mediated SUSY breaking models, values of the SUSY breaking scale Λ below 63 TeV are excluded, independently of tan β. Exclusion limits are also derived for an mSUGRA/CMSSM model, in both the R-parity-conserving and R-parity-violating case. A further interpretation is presented in a framework of natural gauge mediation, in which the gluino is assumed to be the only light coloured sparticle and gluino masses below 1090 GeV are excluded

Measurement of event-plane correlations in sqrt(s_NN)=2.76 TeV lead-lead collisions with the ATLAS detector

See paper for full list of authors - 20 pages plus author list (32 pages total), 15 figures, submitted to Phys. Rev. C., All figures including auxiliary figures can be found at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2012-03/A measurement of event-plane correlations involving two or three event planes of different order is presented as a function of centrality for 7 ub-1 Pb+Pb collision data at sqrt(s_NN)=2.76 TeV, recorded by the ATLAS experiment at the LHC. Fourteen correlators are measured using a standard event-plane method and a scalar-product method, and the latter method is found to give a systematically larger correlation signal. Several different trends in the centrality dependence of these correlators are observed. These trends are not reproduced by predictions based on the Glauber model, which includes only the correlations from the collision geometry in the initial state. Calculations that include the final-state collective dynamics are able to describe qualitatively, and in some cases also quantitatively, the centrality dependence of the measured correlators. These observations suggest that both the fluctuations in the initial geometry and non-linear mixing between different harmonics in the final state are important for creating these correlations in momentum space

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using root s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-pT jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in root s = 8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb(-1). Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate ( single light-flavour) squarks. In mSUGRA/CMSSM models with tan beta = 30, A(0) = -2m(0) and mu > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector

Search for the b(b)over-bar decay of the Standard Model Higgs boson in associated (W/Z)H production with the ATLAS detector

A search for the b (b) over bar decay of the Standard Model Higgs boson is performed with the ATLAS experiment using the full dataset recorded at the LHC in Run 1. The integrated luminosities used are 4.7 and 20.3 fb(-1) from pp collisions at root s = 7 and 8 TeV, respectively. The processes considered are associated (WIZ)H production, where W -> e nu/mu nu, Z -> ee/mu mu, and Z -> nu nu. The observed (expected) deviation from the backgroundonly hypothesis corresponds to a significance of 1.4 (2.6) standard deviations and the ratio of the measured signal yield to the Standard Model expectation is found to be mu = 0.52 +/- 0.32 (stat.) +/- 0.24 (syst.) for a Higgs boson mass of 125.36 GeV. The analysis procedure is validated by a measurement of the yield of (W/Z)Z production with Z -> b (b) over bar in the same final states as for the Higgs boson search, from which the ratio of the observed signal yield to the Standard Model expectation is found to be 0.74 +/- 0.09 (stat.) +/- 0.14 (syst.)