245 research outputs found
Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained with intracellular metabolism, growth control, and signaling. Studying chronological aging in yeast, we reveal a so far overlooked metabolic property that influences aging via the exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically aging cells, resulting in cross-generational metabolic interactions. Then, we used self-establishing metabolically cooperating communities (SeMeCo) as a tool to increase metabolite exchange and observed significant lifespan extensions. The longevity of the SeMeCo was attributable to metabolic reconfigurations in methionine consumer cells. These obtained a more glycolytic metabolism and increased the export of protective metabolites that in turn extended the lifespan of cells that supplied them with methionine. Our results establish metabolite exchange interactions as a determinant of cellular aging and show that metabolically cooperating cells can shape the metabolic environment to extend their lifespan
Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of Kinase Knockouts
A challenge in solving the genotype-to-phenotype relationship is to predict a cell\u27s metabolome, believed to correlate poorly with gene expression. Using comparative quantitative proteomics, we found that differential protein expression in 97 Saccharomyces cerevisiae kinase deletion strains is non-redundant and dominated by abundance changes in metabolic enzymes. Associating differential enzyme expression landscapes to corresponding metabolomes using network models provided reasoning for poor proteome-metabolome correlations; differential protein expression redistributes flux control between many enzymes acting in concert, a mechanism not captured by one-to-one correlation statistics. Mapping these regulatory patterns using machine learning enabled the prediction of metabolite concentrations, as well as identification of candidate genes important for the regulation of metabolism. Overall, our study reveals that a large part of metabolism regulation is explained through coordinated enzyme expression changes. Our quantitative data indicate that this mechanism explains more than half of metabolism regulation and underlies the interdependency between enzyme levels and metabolism, which renders the metabolome a predictable phenotype. Predicting metabolomes from gene expression data is a key challenge in understanding the genotype-phenotype relationship. Studying the enzyme expression proteome in kinase knockouts, we reveal the importance of a so far overlooked metabolism-regulatory mechanism. Enzyme expression changes are impacting on metabolite levels through many changes acting in concert. We show that one can map regulatory enzyme expression patterns using machine learning and use them to predict the metabolome of kinase-deficient cells on the basis of their enzyme expression proteome. Our study quantifies the role of enzyme abundance in the regulation of metabolism and by doing so reveals the potential of machine learning in gaining understanding about complex metabolism regulation
Formation of the in Two-Photon Collisions at LEP
The two-photon width of the meson has been
measured with the L3 detector at LEP. The is studied in the decay
modes , KK, KK,
KK, , , and
using an integrated luminosity of 140 pb at GeV and
of 52 pb at GeV. The result is
(BR) keV. The dependence of the cross section is studied for
GeV. It is found to be better described by a Vector Meson
Dominance model form factor with a J-pole than with a -pole. In addition,
a signal of events is observed at the mass. Upper limits
for the two-photon widths of the , , and are also
given
Search for Scalar Leptons in e+e- collisions at \sqrt{s}=189 GeV
We report the result of a search for scalar leptons in e+e- collisions at 189
GeV centre-of-mass energy at LEP. No evidence for such particles is found in a
data sample of 176 pb^{-1}. Improved upper limits are set on the production
cross sections for these new particles. New exclusion contours in the parameter
space of the Minimal Supersymmetric Standard Model are derived, as well as new
lower limits on the masses of these supersymmetric particles. Under the
assumptions of common gaugino and scalar masses at the GUT scale, we set an
absolute lower limit on the mass of the lightest scalar electron of 65.5 Ge
Search for Low Scale Gravity Effects in e+e- Collisions at LEP
Recent theories propose that quantum gravity effects may be observable at LEP
energies via gravitons that couple to Standard Model particles and propagate
into extra spatial dimensions. The associated production of a graviton and a
photon is searched for as well as the effects of virtual graviton exchange in
the processes: e+e- -> gamma gamma, ZZ, WW, mu mu, tau tau, qq and ee No
evidence for this new interaction is found in the data sample collected by the
L3 detector at LEP at centre-of-mass energies up to 183 GeV. Limits close to 1
TeV on the scale of this new scenario of quantum gravity are set
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 the Probability of Gluon Splitting into Charmed Quarks in Hadronic Z Decays
We have measured the probability, n(g->cc~), of a gluon splitting into a
charm-quark pair using 1.7 million hadronic Z decays collected by the L3
detector. Two independent methods have been applied to events with a three-jet
topology. One method relies on tagging charmed hadrons by identifying a lepton
in the lowest energy jet. The other method uses a neural network based on
global event shape parameters. Combining both methods, we measure n(g->cc~)=
[2.45 +/- 0.29 +/- 0.53]%
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
Measurement of Triple-Gauge-Boson Couplings of the W Boson at LEP
We report on measurements of the triple-gauge-boson couplings of the W boson
in e+e- collisions with the L3 detector at LEP. W-pair, single-W and
single-photon events are analysed in a data sample corresponding to a total
luminosity of 76.7 pb^{-1} collected at centre-of-mass energies between 161 GeV
and 183 GeV. CP-conserving as well as both C- and P-conserving
triple-gauge-boson couplings are determined. The results, in good agreement
with the Standard-Model expectations, confirm the existence of the self
coupling among the electroweak gauge bosons and constrain its structure
Search for Heavy Neutral and Charged Leptons in ee Annihilation at = 183 and 189 GeV
A search for unstable neutral and charged heavy leptons as well as for stable
charged heavy leptons is performed at center-of-mass energies = 183
and 189 GeV with the L3 detector at LEP. No evidence for their existence is
found. We exclude neutral heavy leptons which couple to the electron, muon or
tau family, of the Dirac type for masses below 92.4, 93.3 and 83.3 GeV, and of
the Majorana type for masses below 81.8, 84.1 and 73.5 GeV, respectively. We
exclude unstable charged heavy leptons for masses below 93.9 GeV for a wide
range of the associated neutral heavy lepton mass. If the unstable charged
heavy lepton decays to a light neutrino, we exclude masses below 92.4 GeV. The
production of stable charged heavy leptons with mass less than 93.5 GeV is also
excluded
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