7,321 research outputs found
Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.Fil: Dasuri, Kalavathi. State University Of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University Of Louisiana; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Gavilan, Elena. Universidad de Sevilla; EspañaFil: Zhang, Le. State University Of Louisiana; Estados UnidosFil: Fernandez-Kim, Sun O. K.. State University Of Louisiana; Estados UnidosFil: Bruce Keller, Annadora J.. State University Of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University Of Louisiana; Estados Unido
Primary skin fibroblasts as a model of Parkinson's disease
Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues
Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson
We report first evidence for a fully reconstructed decay mode of the
B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to
mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in
p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider
Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background
of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a
B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability
of a peak of this magnitude occurring by random fluctuation in the search
region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR
Top quark mass measurement using the template method at CDF
We present a measurement of the top quark mass in the lepton+jets and
dilepton channels of decays using the template method. The data
sample corresponds to an integrated luminosity of 5.6 fb of
collisions at Tevatron with TeV, collected with the CDF II
detector. The measurement is performed by constructing templates of three
kinematic variables in the lepton+jets and two kinematic variables in the
dilepton channel. The variables are two reconstructed top quark masses from
different jets-to-quarks combinations and the invariant mass of two jets from
the decay in the lepton+jets channel, and a reconstructed top quark mass
and , a variable related to the transverse mass in events with two
missing particles, in the dilepton channel. The simultaneous fit of the
templates from signal and background events in the lepton+jets and dilepton
channels to the data yields a measured top quark mass of Comment: submitted to Phys. Rev.
Measurement of the Lifetime Difference Between B_s Mass Eigenstates
We present measurements of the lifetimes and polarization amplitudes for B_s
--> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and
light (L) mass eigenstates in the B_s system are separately measured for the
first time by determining the relative contributions of amplitudes with
definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we
obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07
+{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s
and average Gamma_s, of the decay rates of the two eigenstates, the results are
DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47
+{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters
on 16 March 2005; revisions are for length and typesetting only, no changes
in results or conclusion
Measurement of and Production in Collisions at = 1.96 TeV
The Standard Model predictions for and production are
tested using an integrated luminosity of 200 pb of \ppbar collision data
collected at the Collider Detector at Fermilab. The cross sections are measured
selecting leptonic decays of the and bosons, and photons with
transverse energy GeV that are well separated from leptons. The
production cross sections and kinematic distributions for the and
are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR
Precise measurement of the W-boson mass with the CDF II detector
We have measured the W-boson mass MW using data corresponding to 2.2/fb of
integrated luminosity collected in proton-antiproton collisions at 1.96 TeV
with the CDF II detector at the Fermilab Tevatron collider. Samples consisting
of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement
MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most
precise measurement of the W-boson mass to date and significantly exceeds the
precision of all previous measurements combined
Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab
We present a measurement of the ratio of top-quark branching fractions R= B(t
-> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets
and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected
with the Collider Detector at Fermilab during Run II of the Tevatron. The
measurement is derived from the relative numbers of t-tbar events with
different multiplicity of identified secondary vertices. We set a lower limit
of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes
made to be consistent with published versio
Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV
We search for the standard model Higgs boson produced in association with an
electroweak vector boson in events with no identified charged leptons, large
imbalance in transverse momentum, and two jets where at least one contains a
secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1
integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV
recorded by the CDF II experiment at the Tevatron. We find 268 (16) single
(double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are
expected from standard model background processes. We place 95% confidence
level upper limits on the Higgs boson production cross section for several
Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115
GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model
prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s) = 1.96 TeV
We present a measurement of the top quark pair production cross section in
ppbar collisions at sqrt(s)=1.96 TeV using 318 pb^{-1} of data collected with
the Collider Detector at Fermilab. We select ttbar decays into the final states
e nu + jets and mu nu + jets, in which at least one b quark from the t-quark
decays is identified using a secondary vertex-finding algorithm. Assuming a top
quark mass of 178 GeV/c^2, we measure a cross section of 8.7 +-0.9 (stat)
+1.1-0.9 (syst) pb. We also report the first observation of ttbar with
significance greater than 5 sigma in the subsample in which both b quarks are
identified, corresponding to a cross section of 10.1 +1.6-1.4(stat)+2.0-1.3
(syst) pb.Comment: Accepted for publication in Physics Review Letters, 7 page
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