Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells

Objective Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion. Materials and methods We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems. Results Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found. Conclusions In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome.CC BY-NC-ND 4.0Corresponding author: Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. E-mail address: [email protected] (K.-H. Grinnemo).Available online 3 February 2022, Version of Record 5 February 2022The project was funded by Karolinska Institute-Mayo Clinic Collaborative Grant 2013; The Swedish Research Council young investigator: 2013–3590; Stockholm county; The Swedish Research Council; The Family Erling-Persson Foundation; ERC-2018-AdG (834860 EYELETS); Uppsala county; Uppsala County Association against Heart and Lung Diseases; and Higher Education of the Russian Federation (agreement no. 075-15-2020-899).</p

Small Cofactors May Assist Protein Emergence from RNA World: Clues from RNA-Protein Complexes

It is now widely accepted that at an early stage in the evolution of life an RNA world arose, in which RNAs both served as the genetic material and catalyzed diverse biochemical reactions. Then, proteins have gradually replaced RNAs because of their superior catalytic properties in catalysis over time. Therefore, it is important to investigate how primitive functional proteins emerged from RNA world, which can shed light on the evolutionary pathway of life from RNA world to the modern world. In this work, we proposed that the emergence of most primitive functional proteins are assisted by the early primitive nucleotide cofactors, while only a minority are induced directly by RNAs based on the analysis of RNA-protein complexes. Furthermore, the present findings have significant implication for exploring the composition of primitive RNA, i.e., adenine base as principal building blocks

Measurement of the Lifetime of the Tau Lepton

The tau lepton lifetime is measured with the L3 detector at LEP using the complete data taken at centre-of-mass energies around the Z pole resulting in tau_tau = 293.2 +/- 2.0 (stat) +/- 1.5 (syst) fs. The comparison of this result with the muon lifetime supports lepton universality of the weak charged current at the level of six per mille. Assuming lepton universality, the value of the strong coupling constant, alpha_s is found to be alpha_s(m_tau^2) = 0.319 +/- 0.015(exp.) +/- 0.014 (theory)

Measurement of the Tau Branching Fractions into Leptons

Using data collected with the L3 detector near the Z resonance, corresponding to an integrated luminosity of 150pb-1, the branching fractions of the tau lepton into electron and muon are measured to be B(tau->e nu nu) = (17.806 +- 0.104 (stat.) +- 0.076 (syst.)) %, B(tau->mu nu nu) = (17.342 +- 0.110 (stat.) +- 0.067 (syst.)) %. From these results the ratio of the charged current coupling constants of the muon and the electron is determined to be g_mu/g_e = 1.0007 +- 0.0051. Assuming electron-muon universality, the Fermi constant is measured in tau lepton decays as G_F = (1.1616 +- 0.0058) 10^{-5} GeV^{-2}. Furthermore, the coupling constant of the strong interaction at the tau mass scale is obtained as alpha_s(m_tau^2) = 0.322 +- 0.009 (exp.) +- 0.015 (theory)

Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP

The process e+e- -> W+W-gamma is analysed using the data collected with the L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W- candidates containing an isolated hard photon, the W+W-gamma cross section, defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80 +/- 16 fb, consistent with the Standard Model expectation. Including the process e+e- -> nu nu gamma gamma, limits are derived on anomalous contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 < a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2

Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings

Single W boson production in electron-positron collisions is studied with the L3 detector at LEP. The data sample collected at a centre-of-mass energy of \sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1. Events with a single energetic lepton or two acoplanar hadronic jets are selected. Within phase-space cuts, the total cross-section is measured to be 0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation. Including our single W boson results obtained at lower \sqrt{s}, the WWgamma gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma = 0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13

Search for an invisibly decaying Higgs boson in e^+e^- collisions at \sqrt{s} = 183 - 189 GeV

A search for a Higgs boson decaying into invisible particles is performed using the data collected at LEP by the L3 experiment at centre-of-mass energies of 183 GeV and 189 GeV. The integrated luminosities are respectively 55.3 pb^-1 and 176.4 pb^-1. The observed candidates are consistent with the expectations from Standard Model processes. In the hypothesis that the production cross section of this Higgs boson equals the Standard Model one and the branching ratio into invisible particles is 100%, a lower mass limit of 89.2 GeV is set at 95% confidence level

Search for Neutral Higgs Bosons of the Minimal Supersymmetric Standard Model in e+e- Interactions at \sqrt{s} = 189 GeV

A search for the lightest neutral scalar and neutral pseudoscalar Higgs bosons in the Minimal Supersymmetric Standard Model is performed using 176.4 pb^-1 of integrated luminosity collected by L3 at a center-of-mass energy of 189 GeV. No signal is observed, and the data are consistent with the expected Standard Model background. Lower limits on the masses of the lightest neutral scalar and pseudoscalar Higgs bosons are given as a function of tan(beta). Lower mass limits for tan(beta)>1 are set at the 95% confidence level to be m_h > 77.1 GeV and m_A > 77.1 GeV

Measurement of Bose-Einstein Correlations in e+e- -> W+W- at root(s)=189GeV

We investigate Bose-Einstein correlations (BEC) in W-pair production at root(s)=189GeV using the L3 detector at LEP. We observe BEC between particles from a single W decay in good agreement with those from a light-quark Z decay sample. We investigate their possible existence between particles coming from different W's. No evidence for such inter-W BEC is found

Search for Extra Dimensions in Boson and Fermion Pair Production in e+e- Interactions at LEP

Extra spatial dimensions are proposed by recent theories that postulate the scale of gravity to be of the same order as the electroweak scale. A sizeable interaction between gravitons and Standard Model particles is then predicted. Effects of these new interactions in boson and fermion pair production are searched for in the data sample collected at centre-of-mass energies above the Z pole by the L3 detector at LEP. In addition, the direct production of a graviton associated with a Z boson is investigated. No statistically significant hints for the existence of these effects are found and lower limits in excess of 1 TeV are derived on the scale of this new theory of gravity